Explore the mechanism of puerarin to improve diabetic peripheral neuropathy in rats based on AGEs/RAGE signaling pathway

HAO Lu; SHI Mingyang; CHEN Yan; YANG Shan

doi:10.12173/j.issn.1004-5511.202410034

Abstract：Objective To explore the ameliorative effect of puerarin on diabetic peripheral neuropathy(DPN)in rats and its possible mechanism.Methods A total of 50 SD rats were randomly divided into control group,model group(DPN model was constructed),low-dose puerarin group(20 mg/kg puerarin was intraperitoneally injected after DPN model was constructed),high-dose puerarin group(40 mg/kg puerarin was intraperitoneally injected after DPN model was constructed),RAGE inhibitor group(0.5 mg/kg FPS-ZM1 was intraperitoneally injected after DPN model was constructed),with 10 rats in each group.After administration,the fasting blood glucose,blood lipid index and inflammatory index of rats in each group were measured,and mechanical pain threshold,thermal pain threshold,motor nerve conduction velocity(MNCV)and sensory nerve conduction velocity(SNCV)were detected,the pathological changes of sciatic nerve in each group were observed through HE stain and transmission electron microscope.The content of AGEs and the expression of receptor for advanced glycation end products(RAGE)in sciatic nerve of rats in each group was detected by colorimetry and Western blot.Results Compared with the control group,fasting blood glucose,total cholesterol(TC),triglyceride(TG)and low-density lipoprotein(LDL)levels of rats in model group were significantly increased,high-density lipoprotein(HDL)levels were significantly decreased,the levels of inflammatory factors such as interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were significantly increased,mechanical pain threshold,MNCV and SNCV were significantly decreased,heat pain threshold was significantly increased,the injury of sciatic nerve and pathological change of myelin sheath were obvious,AGEs content and RAGE protein relative expression level in sciatic nerve were significantly increased(P＜0.05).Compared with model group,fasting blood glucose,TC,TG and LDL levels were significantly decreased,HDL levels were significantly increased,IL-1β,IL-6 and TNF-α contents were significantly decreased,mechanical pain threshold,MNCV and SNCV were significantly increased,and thermal pain threshold was significantly decreased,the injury of sciatic nerve and the pathological structure of myelin sheath of rats were improved to varying degrees,AGEs content and RAGE protein relative expression in sciatic nerve were decreased significantly(P＜0.05)in low-dose puerarin group and high-dose puerarin group.Compared with the puerarin low dose group,the effect of puerarin high-dose group and RAGE inhibitor group was more obvious.Conclusion Puerarin can improve blood glucose and blood lipid levels in DPN rats,reduce serum inflammatory factors,neurological damage and histological damage,and this mechanism may be related to inhibiting the activation of AGEs/RAGE signaling pathway.