温通活血乳膏调控PERK-eIF2α通路介导内质网应激改善糖尿病周围神经病变的研究OA

Objective To investigate the effects of Wentong Huoxue(WTHX)Ointment on the endoplasmic reticulum stress signaling pathway in the sciatic nerve of rats with diabetic peripheral neuropathy(DPN),and to explore its potential mechanism of action in alleviating diabetes-induced peripheral neuropathy.Methods Sixty SD rats were used in the study,and 10 rats were randomly selected as the blank group and given basic diet by using the random number table method.The other rats were given high sugar and high-fat diet for 6 weeks,and streptozotocin was injected intraperitoneally to establish the diabetes model.After the model was established,the rats were given high sugar and high-fat diet for 8 weeks.When the sensory or motor conduction velocity of sciatic nerve in both lower limbs slowed down by more than 11%,it was judged as the DPN rat model.DPN rats were randomly divided into five groups:model group,model+blank cream group,model+Wentong Huoxue cream low-dose group(WTHX low-dose group),model+Wentong Huoxue cream medium dose group(WTHX medium dose group),model+Wentong Huoxue cream high-dose group(WTHX high-dose group),10 rats in each group,with drug intervention for 4 weeks.In this experiment,the general conditions of rats in each group were observed,and blood glucose levels were measured before and after treatment.After treatment completion,the hot plate tail-flick test was performed.Pathological changes in the sciatic nerve were observed under light microscopy,and ultrastructural changes in the sciatic nerve and gastrocnemius muscle were examined under electron microscopy.The protein expression levels of p-PERK,PERK,p-eIF2α,eIF2α,ATF4,CHOP,and Caspase-3 in the sciatic nerve were detected by Western blot.Cell apoptosis in the sciatic nerve was assessed using the TUNEL method.Results Compared with the blank group,the model group showed reduced thermal sensitivity and prolonged tail-flick latency(P＜0.001).Significant pathological and ultrastructural changes were observed in the sciatic nerve and gastrocnemius muscle.The expression levels of p-PERK,p-eIF2α,ATF4,CHOP,and Caspase-3 proteins were significantly upregulated(P＜0.001).Compared with the model group,the low-,medium-,and high-dose WTHX groups exhibited shortened tail-flick latency(P＜0.01)and significantly ameliorated pathological damage and ultrastructural disorders in the sciatic nerve and gastrocnemius muscle.The high-dose WTHX group significantly downregulated the expression levels of p-PERK,p-eIF2α,ATF4,CHOP,and Caspase-3 proteins in the sciatic nerve(P＜0.01),thereby alleviating endoplasmic reticulum stress.Conclusion WTHX Ointment exerts dual protective effects on nerves and muscles in DPN by regulating the PERK/eIF2α/ATF4/CHOP pathway to inhibit endoplasmic reticulum stress-related apoptosis.