Hong Pan1,2, Haipeng Huang1, Liying Zhang1, Shiqi Ma1, Hongmei Yang1,3, Hongfeng Wang1. 1. College of Acupuncture and Massage, Changchun University of Chinese Medicine, Changchun, China. 2. Pediatrics, Beijing First Hospital of Integrated Chinese and Western Medicine, Beijing, China. 3. Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, China.
Abstract
BACKGROUND: The clinical efficacy of electroacupuncture in treating diabetic peripheral neuropathy (DPN) is significant, but the underlying mechanism of action is not clear. Considering that glucose-regulated protein 78 (GRP78) and caspase-12 are major proteins participating in cell apoptosis, we investigated the effects of "adjusting internal organs and dredging channel" electroacupuncture therapy on GRP78 and caspase-12 levels in streptozotocin (STZ)-diabetic rats to elucidate the mechanism of action. METHODS: Rats were first divided into two groups: one group was rendered diabetic with a single injection of 50 mg/kg STZ, whereas the other normal control group was injected with an equivalent volume of citrate buffer. The STZ-diabetic rats were randomly divided into three groups: model control and electroacupuncture- and mecobalamin-treated groups. After 12 weeks treatment, the therapeutic efficacy of electroacupuncture was assessed using sciatic nerves isolated from rats. In the electroacupuncture group, rats were treated by electroacupuncture for 20 minutes once daily for 6 days each week, with 1 day off, for 12 consecutive weeks. The selected acupressure points include bilateral acupressure points of BL13 (Fehu), BL20 (Pishu), BL23 (Shenshu), LI4 (Hegu), LR3 (faichong), ST36 (Zusanli), and SP6 (Sanyiniiao). Acupressure points were stimulated using a HuaTuo SDZ-V Electric Acupuncture Therapy Apparatus. The acupressure points of BL13 and BL23, as well as SP6 and LR3, were connected on the same side with a dilatational wave of 3 Hz (frequency ratio of 1 : 5) to stimulate the parts of the body to the extent that could be tolerated by the rat. As for the mecobalamin-treated groups, mecobalamin was administrated to rats intragastrically at a dose of 20 mg/kg once daily for 12 consecutive weeks. Immunofluorescence and western blot analysis were used to determine GRP78 and caspase-12 levels in sciatic nerves. In addition, cell apoptosis in sciatic nerves was determined using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay. RESULTS: Electroacupuncture markedly reduced the pathological injury to sciatic nerves in STZ-diabetic rats. Moreover, electroacupuncture significantly downregulated GRP78 and caspase-12 and reduced cell apoptosis of sciatic nerves in DPN rats. CONCLUSIONS: Electroacupuncture improved DPN by downregulating GRP78 and caspase-12 and reducing cell apoptosis of sciatic nerves in STZ-diabetic rats, and further inhibited the occurrence of endoplasmic reticulum stress, thus preventing sciatic nerve injuries.
BACKGROUND: The clinical efficacy of electroacupuncture in treating diabetic peripheral neuropathy (DPN) is significant, but the underlying mechanism of action is not clear. Considering that glucose-regulated protein 78 (GRP78) and caspase-12 are major proteins participating in cell apoptosis, we investigated the effects of "adjusting internal organs and dredging channel" electroacupuncture therapy on GRP78 and caspase-12 levels in streptozotocin (STZ)-diabeticrats to elucidate the mechanism of action. METHODS:Rats were first divided into two groups: one group was rendered diabetic with a single injection of 50 mg/kg STZ, whereas the other normal control group was injected with an equivalent volume of citrate buffer. The STZ-diabeticrats were randomly divided into three groups: model control and electroacupuncture- and mecobalamin-treated groups. After 12 weeks treatment, the therapeutic efficacy of electroacupuncture was assessed using sciatic nerves isolated from rats. In the electroacupuncture group, rats were treated by electroacupuncture for 20 minutes once daily for 6 days each week, with 1 day off, for 12 consecutive weeks. The selected acupressure points include bilateral acupressure points of BL13 (Fehu), BL20 (Pishu), BL23 (Shenshu), LI4 (Hegu), LR3 (faichong), ST36 (Zusanli), and SP6 (Sanyiniiao). Acupressure points were stimulated using a HuaTuo SDZ-V Electric Acupuncture Therapy Apparatus. The acupressure points of BL13 and BL23, as well as SP6 and LR3, were connected on the same side with a dilatational wave of 3 Hz (frequency ratio of 1 : 5) to stimulate the parts of the body to the extent that could be tolerated by the rat. As for the mecobalamin-treated groups, mecobalamin was administrated to rats intragastrically at a dose of 20 mg/kg once daily for 12 consecutive weeks. Immunofluorescence and western blot analysis were used to determine GRP78 and caspase-12 levels in sciatic nerves. In addition, cell apoptosis in sciatic nerves was determined using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay. RESULTS: Electroacupuncture markedly reduced the pathological injury to sciatic nerves in STZ-diabeticrats. Moreover, electroacupuncture significantly downregulated GRP78 and caspase-12 and reduced cell apoptosis of sciatic nerves in DPNrats. CONCLUSIONS: Electroacupuncture improved DPN by downregulating GRP78 and caspase-12 and reducing cell apoptosis of sciatic nerves in STZ-diabeticrats, and further inhibited the occurrence of endoplasmic reticulum stress, thus preventing sciatic nerve injuries.