Yue Sun1, Jian Liu2, Lei Wan2, Fang Wang1, Yajun Qi1. 1. Graduate School, Anhui University of Chinese Medicine, Hefei 230038, China. 2. First Affiliated Hospital, Anhui University of Chinese Medicine, Hefei 230031, China.
Abstract
OBJECTIVE: To observe the changes in cardiac function, peripheral blood B and T lymphocyte attenuator (BTLA) and oxidative stress related indicators in rheumatoid arthritis(RA) patients, thus to explore the mechanism underlying the improving effect of Xinfeng Capsule (XFC) on cardiac function. METHODS: The study enrolled 100 RA patients and divided them randomly into 2 groups, XFC treatment group and leflunomide (LEF) control group (n=50 per group). The treatment lasted 30 days for one course. Other 40 healthy people from Medical Examination Center were included as a normal control (NC) group. Flow cytometry was used to detect the expression and activation level of BTLA, Westergren method was used to determine erythrocyte sedimentation rate (ESR), and automatic biochemical analyzer to examine high sensitivity C-reactive protein (hs-CRP) and rheumatoid factor (RF). ELISA method was performed to observe related cytokines (IL-1β, IL-17, IL-35, IFN-γ) and markers of oxidative stress such as total antioxidant capacity (TAOC), malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH). Echocardiography was utilized to survey cardiac function parameters including heart ejection fraction (EF%), stroke volume (SV%), fractional shortening (FS%), E peak velocities (E) and A peak velocities (A) of mitral valve flow, and the ratio of filling fraction of E and A (E/A). RESULTS: Compared with the NC group, EF%, E peak velocity, E/A were significantly reduced while A peak velocity increased in RA patients, and FS% was not found obviously different. In addition, IL-1β, IL-17 and inflammatory indexes like ESR, CRP increased while BTLA, IL-35, IFN-γ decreased significantly; Serum ROS, MDA rose and SOD, GSH dropped significantly in RA patients. Correlation analysis showed that the cardiac function parameters EF, FS were negatively correlated with CD24⁺ cells and CD19⁺CD24⁺ cells, that E/A was positively correlated with BTLA, that A peak velocity was positively related to CD19⁺ cells, that EF was positively related to ROS, that SV was positively related with MDA, SOD, that E peak velocity was negatively correlated with TAOC. After drug intervention, XFC treatment group got 86% total effective rate. XFC obviously improved cardiac function regarding EF%, FS%, E peak, E/A and other parameters, increased serum SOD, GSH capacity, eliminated ROS, MDA, increased BTLA, IL-35, IFN-γ, and reduced IL-1β, IL-17. Compared with LEF group, XFC had a better improving effect on DAS28 and cardiac function parameters. CONCLUSION:XFC can increase BTLA expression of CD19⁺ and CD24⁺ B cells and reduce B cell-mediated abnormal humoral immunity and oxidative stress damage, thus improving cardiac function and quality of life.
RCT Entities:
OBJECTIVE: To observe the changes in cardiac function, peripheral blood B and T lymphocyte attenuator (BTLA) and oxidative stress related indicators in rheumatoid arthritis(RA) patients, thus to explore the mechanism underlying the improving effect of Xinfeng Capsule (XFC) on cardiac function. METHODS: The study enrolled 100 RApatients and divided them randomly into 2 groups, XFC treatment group and leflunomide (LEF) control group (n=50 per group). The treatment lasted 30 days for one course. Other 40 healthy people from Medical Examination Center were included as a normal control (NC) group. Flow cytometry was used to detect the expression and activation level of BTLA, Westergren method was used to determine erythrocyte sedimentation rate (ESR), and automatic biochemical analyzer to examine high sensitivity C-reactive protein (hs-CRP) and rheumatoid factor (RF). ELISA method was performed to observe related cytokines (IL-1β, IL-17, IL-35, IFN-γ) and markers of oxidative stress such as total antioxidant capacity (TAOC), malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH). Echocardiography was utilized to survey cardiac function parameters including heart ejection fraction (EF%), stroke volume (SV%), fractional shortening (FS%), E peak velocities (E) and A peak velocities (A) of mitral valve flow, and the ratio of filling fraction of E and A (E/A). RESULTS: Compared with the NC group, EF%, E peak velocity, E/A were significantly reduced while A peak velocity increased in RApatients, and FS% was not found obviously different. In addition, IL-1β, IL-17 and inflammatory indexes like ESR, CRP increased while BTLA, IL-35, IFN-γ decreased significantly; Serum ROS, MDA rose and SOD, GSH dropped significantly in RApatients. Correlation analysis showed that the cardiac function parameters EF, FS were negatively correlated with CD24⁺ cells and CD19⁺CD24⁺ cells, that E/A was positively correlated with BTLA, that A peak velocity was positively related to CD19⁺ cells, that EF was positively related to ROS, that SV was positively related with MDA, SOD, that E peak velocity was negatively correlated with TAOC. After drug intervention, XFC treatment group got 86% total effective rate. XFC obviously improved cardiac function regarding EF%, FS%, E peak, E/A and other parameters, increased serum SOD, GSH capacity, eliminated ROS, MDA, increased BTLA, IL-35, IFN-γ, and reduced IL-1β, IL-17. Compared with LEF group, XFC had a better improving effect on DAS28 and cardiac function parameters. CONCLUSION: XFC can increase BTLA expression of CD19⁺ and CD24⁺ B cells and reduce B cell-mediated abnormal humoral immunity and oxidative stress damage, thus improving cardiac function and quality of life.