Discussion of mechanism of Compound Qiying Granules based on PERK/Nrf2 pathway in treating diabetic peripheral neuropathy
CHEN Chen1 HU Yan1 LIU Tao2 HU Xiaoling2
1.The Fourth Clinical Medical College, Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China;
2.Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Xinjiang Uygur Autonomous Region, Urumqi 830000, China
Abstract：Objective To investigate the mechanism of Compound Qiying Granules on diabetic peripheral neuropathy (DPN) rats based on PERK/Nrf2 pathway. Methods A total of 72 SPF male Wistar rats weight 180-220 g and aged eight weeks were divided into normal control group, model group, positive drug group, and Compound Qiying Granules low-dose, medium-dose, high-dose groups by random number table method, with 12 rats in each group. Except the normal control group, the other five groups were continuously fed high-fat diet, and streptozotocin (30 mg/kg) was injected eight weeks later, and then rats with fasting blood glucose ＞11.1 mol/L were selected to continue high-fat diet for four weeks to build DPN model. After the DPN modeling was successful, Compound Qiying Granules low-dose, medium-dose, high-dose groups were given 1.17, 2.34, 4.68 g/kg Compound Qiying Granules, respectively, the positive drug group was given Trimethylamine Oxide (110 mg/kg), 2 ml/time, once a day, the normal control group and model group were given the same amount of double steaming water. After four weeks of intervention, blood glucose changes before and after intervention in the six groups were compared, and hematoxylin-eosin staining of sciatic nerve in the six groups was observed. Glucose regulatory protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), activating transcription factor 4 (ATF4), nuclear factor-erythroid 2-related factor 2 (Nrf2), C/EBP homologous protein (CHOP), cysteine aspartic acid specific protease-3 (caspase-3) in six groups of sciatic nerves were detected by Western blot. Results In the normal control group, the structure of myelinated nerve fibers was complete, the distribution was uniform, the arrangement was regular, the shape and structure of axons, myelin sheath, and nerve membranes were good and complete, and the shape and structure of endoneurals were normal. In the model group, there were loss and decrease of myelinated nerve fibers, partial disordered arrangement, partial axonal degeneration, segmental demyelination, thickening of nerve membrane, and hyperplasia of endoneural collagen fibers. The degree of degeneration, demyelination, thickening of nerve membrane, and hyperplasia of nerve intima in Compound Qiying Granules low-dose, medium-dose, high-dose groups were less than those in model group. After the successful DPN modeling, the blood glucose of the model group was higher than that of the normal control group (P＜0.05), and there was no statistical significance in blood glucose of Compound Qiying Granules low-dose, medium-dose, high-dose groups compared with the model group (P＞0.05). After four weeks of drug intervention, the blood glucose of model group was higher than that of normal control group, and those of Compound Qiying Granules low-dose, medium-dose, high-dose groups were lower than those of model group, and those of Compound Qiying Granules medium-dose, high-dose groups were lower than those in Compund Qiying Granules low-dose group (P＜0.05). GRP78, p-PERK, ATF4, CHOP, and caspase-3 of sciatic nerve tissues in model group were higher than those in normal control group, and Nrf2 was lower than that in normal control group (P＜0.05). GRP78, ATF4, and CHOP in Compound Qiying Granules medium-dose, high-dose groups were lower than those in model group, and Nrf2 were higher than those in model group; p-PERK and caspase-3 in Compound Qiying Granules high-dose group were lower than those in model group (P＜0.05). ATF4 and CHOP of Compound Qiying Granules high-dose group were lower than those of Compound Qiying Granules low-dose group, CHOP of Compound Qiying Granules medium-dose group was lower than that of Compound Qiying Granules low-dose group (P＜0.05). Conclusion Compound Qiying Granules has certain hypoglycemic and neuroprotective effects, and its mechanism may be to relieve endoplasmic reticulum stress by inhibiting PERK/Nrf2 pathway.
陈臣1 胡燕1 刘涛2 胡晓灵2. 基于PERK/Nrf2通路探讨复方芪鹰颗粒治疗糖尿病周围神经病变的机制[J]. 中国医药导报, 2023, 20(27): 7-11.
CHEN Chen1 HU Yan1 LIU Tao2 HU Xiaoling2. Discussion of mechanism of Compound Qiying Granules based on PERK/Nrf2 pathway in treating diabetic peripheral neuropathy. 中国医药导报, 2023, 20(27): 7-11.
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