基于Keap1/Nrf2/HO-1信号轴探讨"治神调髓"针刺改善缺血性脑卒中大鼠氧化应激损伤的作用机制OA
Mechanism of"Zhishen Tiaosui"acupuncture on improving oxidative stress injury in rats with ischemic stroke based on the Keap1/Nrf2/HO-1 signaling axis
目的:探讨"治神调髓"针刺通过Keap1/Nrf2/HO-1信号轴,改善缺血性脑卒中(ischemic stroke,IS)大鼠氧化应激损伤的作用机制.方法:选用90只SPF级6～8周龄(180～220 g)雄性SD大鼠,设立假手术组、模型组、普通针刺组、"治神调髓"针刺组、西药组(依达拉奉右莰醇组),采用改良线栓法建立大鼠大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)模型,采用Zea-longa神经功能评分方法评估神经功能缺损,TTC检测脑梗死面积,H&E染色观察脑组织病理损伤,尼氏染色检测脑组织病理改变,透射电镜观察缺血脑组织神经元超微结构及线粒体形态,ELISA检测血清中总超氧化物歧化酶(total superoxide dismutase,T-SOD)、丙二醛(malondialdehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)、活性氧(reactive oxygen species,ROS)含量,Western blot检测脑组织Keap1、Nrf2、HO-1蛋白表达水平.结果:与模型组相比,"治神调髓"针刺组大鼠神经功能明显改善,梗死面积减少;神经元损伤减轻;尼氏体数量增多,超微结构改善;血清中T-SOD、GSH-PX升高(P<0.01),MDA、ROS含量降低(P<0.01),脑组织Keap1蛋白表达水平降低(P<0.01),Nrf2、HO-1蛋白表达水平升高(P<0.01).结论:"治神调髓"针刺可能通过Keap1/Nrf2/HO-1信号轴,有效减轻IS大鼠的氧化应激损伤,治疗效果与依达拉奉右莰醇相当,明显优于普通针刺,为临床提供了一种非药物的有效替代方案.
Objective:To investigate the mechanism of"Zhishen Tiaosui"acupuncture improving oxidative stress injury in rats with ischemic stroke(IS)through the Keap1/Nrf2/HO-1 signaling axis.Methods:A total of 90 SPF male SD rats aged 6‒8 weeks(180‒220 g)were selected and divided into the sham operation group,the model group,the conventional acupuncture group,the"Zhishen Tiaosui"acupuncture group,and the Western medicine group(edaravone dexborneol group),the middle cerebral artery occlusion(MCAO)model by modified suture method were established,the neurological deficit score was evaluated by Zea-Longa neurological deficit score method,the cerebral infarction area was detected by TTC,the pathological damages of brain tissue were observed by H&E staining,the pathological changes of brain tissue were detected by Nissl staining,and the ultrastructure of isch-emic brain tissue neurons,including mitochondrial morphology,was observed by transmission electron microscopy.The contents of total superoxide dismutase(T-SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-PX),and reactive oxygen spe-cies(ROS)in serum were detected by ELISA.The protein expression levels of Keap1,Nrf2,and HO-1 in brain tissue were detect-ed by Western blot.Results:Compared to the model group,the neurological function of the rats in the"Zhishen Tiaosui"acupunc-ture group were significantly improved,and the infarct area was reduced.Neuronal damage was alleviated,the number of Nissl bodies was increased,and the ultrastructure was improved.The levels of T-SOD and GSH-PX in serum were increased(P<0.01),the contents of MDA and ROS were decreased(P<0.01),the expression level of Keap1 protein in brain tissue was de-creased(P<0.01),and the expression levels of Nrf2 and HO-1 proteins were increased(P<0.01).Conclusion:The"Zhishen Tiaosui"acupuncture may effectively reduce the oxidative stress injury of IS rats through the Keap1/Nrf2/HO-1 signaling axis.The therapeutic effect is comparable to that of edaravone dexborneol and is significantly better than that of conventional acupunc-ture.It provides a non-drug effective alternative for clinical practice.
李玲玲;徐银凤;谢姗珊;智勇
新疆医科大学中医学院,新疆 乌鲁木齐 830054新疆医科大学中医学院,新疆 乌鲁木齐 830054新疆医科大学中医学院,新疆 乌鲁木齐 830054新疆医科大学中医学院,新疆 乌鲁木齐 830054
医药卫生
针刺缺血性脑卒中氧化应激治神调髓
AcupunctureIschemic strokeOxidative stressZhishen Tiaosui
《海南医科大学学报》 2026 (5)
345-354,10
This study was supported by the National Natural Science Foundation of China(82560970,82060894)Xinjiang Uygur Autonomous Region Regional Collaborative Innovation Project(2022E01043) 国家自然科学基金(82560970,82060894)新疆维吾尔自治区区域协同创新专项(2022E01043)
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