补阳还五汤对缺血再灌注脑损伤大鼠内质网应激-自噬的影响  

Effect of Buyang Huanwu Decoction on endoplasmic reticulum stress-autophagy in rats with ischemia-reperfusion brain injury

作　　者：程一升 陶壮俊 王苹莉 CHENG Yisheng;TAO Zhuangjun;WANG Pingli(Department of Neurology,Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine,Wenzhou 325000,China;Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]温州市中西医结合医院神经内科,浙江温州325000 [2]浙江中医药大学,浙江杭州310053

出　　处：《中国现代医生》2022年第11期34-37,98,F0003,共6页China Modern Doctor

基　　金：浙江省中医药科学研究基金项目(2020ZB241)。

摘　　要：目的探讨补阳还五汤治疗对缺血再灌注脑损伤大鼠内质网应激及自噬的影响。方法建立大鼠大脑中动脉闭塞模型(MCAO)后分为假手术组、模型组及治疗组,治疗组灌胃补阳还五汤浓煎剂,模型组和假手术组均灌胃生理盐水,连续灌胃7 d。给药7 d后,采用改良的Berderson行为学评分方法对大鼠进行评分观察神经功能损伤情况,氯化三苯基四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)染色观察脑梗死面积,qPCR检测脑组织葡萄糖调节蛋白78(glucose regulated protein 78 kD,GRP78)、蛋白激酶RNA样内质网激酶(protein kinase RNA-like endoplasmic reticulum kinase,PERK)、真核起始因子2α(eukaryotic initiation factor 2α,elF2α)、自噬相关基因12(autophagy related gene 12,ATG12)mRNA表达情况,透射电镜检查脑组织梗死周边交界区自噬小体情况,HE染色观察脑组织病理损伤。结果模型组大鼠的脑组织损失部分塌陷,硬度差,呈苍白色;模型组和治疗组的Berderson行为学评分明显高于假手术组(P<0.01),治疗组明显低于模型组(P<0.01);模型组脑梗死面积较治疗组明显增多(P<0.01);与模型组比较,治疗组的GRP78、PERK、elF2α、ATG12 mRNA表达明显减少(P<0.05);治疗组自噬小体数量较模型组明显减少;治疗组病理损伤较模型组明显减轻。结论补阳还五汤可以改善大鼠脑缺血再灌注脑损伤,其机制可能是通过调控内质网应激-自噬发挥作用。Objective To investigate the effect of Buyang Huanwu Decoction on endoplasmic reticulum stress and autophagy in rats with ischemia-reperfusion brain injury.Methods The rat model of middle cerebral artery occlusion(MCAO)was established and divided into sham operation group,model group,and treatment group.The treatment group was intragastrically administered with Buyang Huanwu concentrated decoction.The model group and sham operation group were intragastrically administered with normal saline.They were intragastrically administered for seven consecutive days.After seven days of the administration,the neurological impairment of rats was observed by the modified Berderson behavioral scoring method.The cerebral infarction area was observed by 2,3,5-triphenyltetrazolium chloride(TTC)staining.The mRNA expression of glucose regulated protein 78 kD(GRP78),protein kinase RNA-like endoplasmic reticulum kinase(PERK),eukaryotic initiation factor 2α(elF2α),and autophagy-related gene 12(ATG12)in brain tissue was detected by qPCR.The autophagosomes at the peri-infarct junction of brain tissue were examined by transmission electron microscopy.The pathological damage of brain tissue was observed by HE staining.Results The brain tissue loss area of rats in the model group was collapsed with poor hardness and pale color.The Berderson behavioral score in the model group and the treatment group was significantly higher than that in the sham operation group(P<0.01).And the Berderson behavioral score in the treatment group was significantly lower than that in the model group(P<0.01).The cerebral infarction area in the model group was significantly higher than in the treatment group(P<0.01).Compared with the model group,the expression of GRP78,PERK,elF2α,and ATG12 mRNA in the treatment group was significantly reduced(P<0.05).The number of autophagosomes in the treatment group was significantly reduced;the pathological injury in the treatment group was significantly alleviated.Conclusion Buyang Huanwu Decoction can improve cere-bral is

关 键 词：缺血再灌注脑损伤 补阳还五汤 内质网应激 自噬 

分 类 号：R255.2[医药卫生—中医内科学]