电针对帕金森病模型大鼠内质网应激IRE1α-ASK1-JNK通路的影响

摘要

目的:探讨内质网应激介导的IRE1α-ASK1-JNK通路在鱼藤酮诱导的帕金森病(PD)模型大鼠中的作用及电针干预治疗对该通路的影响.方法:将120只健康雄性SD大鼠随机分为正常组、假手术组、模型组、电针预治疗组、电针治疗7d组、电针治疗14d组、电针治疗21d组、电针治疗28d组,每组15只,采用颈背部皮下注射鱼藤酮法制备帕金森病模型,假手术组只注射不含鱼藤酮的等量葵花油乳化液.正常组、模型组、假手术组不做任何治疗;电针治疗组在造模完成后选取“风府”、“太冲”穴给予电针治疗;电针预治疗组电针治疗7d后再造模.采用旷场试验检测大鼠行为学改变,并用Western-blot法检测大鼠中脑黑质内IRE1α、ASK1、p-JNK蛋白表达的变化.结果:模型组大鼠表现出明显的PD症候群特征,电针干预后模型大鼠行为学评分改善明显(P＜0.01).模型组大鼠黑质IRE1α、ASK1、p-JNK蛋白表达较正常组和假手术组显著增高(均P＜0.01);与模型组相比,电针预治疗组和电针治疗7d、14d、21d、28d组IRE1α、ASK1、p-JNK蛋白表达水平显著降低(均P＜ 0.01).结论:电针防治帕金森病的机制可能与电针能明显抑制内质网应激通路IRE1 α-ASK 1-JNK的活性,保护多巴胺能神经元免于凋亡有关.%Objective:To explore the action mechanism of the IRE1α-ASK1-JNK pathway mediated by endoplasmic reticulum stress (ERS) in rats with Parkinson's disease induced by rotenone and the effects of electroacupuncture on it.Method:Male SD rats were randomly divided into normal group,sham-operation group,model group,pretreatment group,four EA groups (treatment for 7 days,14 days,21 days,28 days),15 rats in each group.PD model was induced by subcutaneous injection of rotenone at the rat's nape,and rats in the sham-operation group were injected with sun-flower oil that did not include rotenone.Rats in the EA groups were treated by EA at "Fengfu" (GV16) and "Taichong" (LR3) for 20 min with continuous wave,intensity just evoke slight twitch in the leg of rat.While the normal group,sham-operation group and model group were not treated.The treatment was given once a day for EA groups of 7 days,14 days,21 days and 28 days.Rats in the pretreatment group received the same treatment as the EA groups for 7 days and then established the model.Openfield test was used to evaluate ethology changes of PD rats.The expression of IRE1α,ASK1 and p-JNK protein in substantia nigra was tested by Western-blot method.Result:Rats in model group showed obvious characteristics of PD syndrome.The behavioral score of PD rats after EA intervention was significantly improved (P＜0.01).Compared with normal group and sham-operation group,the IRE1α,ASK1 and p-JNK protein expressed in model group increased significantly (all P＜0.01).Compared with model group,the IRE1α,ASK1 and p-JNK protein expressed in EA groups and pretreatment group significantly decreased (all P＜ 0.01).Conclusion:The mechanism of EA in preventing and treating Parkinson's disease may be related to that EA could inhibit the activation of IRE1α-ASK1-JNK pathway,which can protect the dopaminergic neurons from apoptosis.