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目的探讨养阴通脑颗粒减轻脑缺血再灌注损伤的可能作用机制。方法将162只SD大鼠随机分为假手术组、模型组、养阴通脑颗粒组,每组54只。模型组和养阴通脑颗粒组通过大脑中动脉局灶性栓塞手术建立脑缺血再灌注损伤模型。养阴通脑颗粒组造模成功后每12 h给予养阴通脑颗粒0.5 g/kg灌胃,假手术组和模型组给予等量生理盐水。于造模后12、24、48、72 h观察大鼠神经功能缺损评分、大脑海马葡萄糖调节蛋白78(GRP78)和蛋白激酶R样内质网激酶(PERK)蛋白及mRNA表达及真核生物翻译起始因子2α(e IF2α)、内质网源性转录因子(chop)、转录激活因子4(ATF4)mRNA表达;并于造模后72 h检测脑梗死体积及脑组织海马区病理变化。结果与假手术比较,模型组大鼠各时间点神经功能缺损评分,GRP78、PERK蛋白及mRNA表达,e IF2α、chop、ATF4 mRNA表达均明显升高,脑梗死体积明显增大(P<0.01);与模型组比较,养阴通脑颗粒组各时间点神经功能缺损评分,PERK蛋白及PERK、e IF2α、chop、ATF4 mRNA表达明显降低,GRP78蛋白和mRNA表达均显著升高,脑梗死体积明显缩小(P<0.05或P<0.01)。结论养阴通脑颗粒可能通过调节海马内质网相关因子表达,抑制内质网应激,从而减轻脑缺血再灌注损伤。
Objective To investigate the possible mechanism of Yangyintongnao Granule in reducing cerebral ischemia-reperfusion injury. Methods 162 SD rats were randomly divided into sham operation group, model group and Yangyin Tongnao granule group, with 54 rats in each group. Model group and Yangyin Tongnao granule group were established cerebral ischemia-reperfusion injury model by focal embolization of middle cerebral artery. Yangyin Tongnao granule group model was given every 12 hours after Yangyin Tongnao granules 0.5 g / kg gavage, sham operation group and model group were given the same amount of saline. The rats were sacrificed at 12, 24, 48 and 72 h after operation to observe the neurological deficit score, the protein and mRNA expression of GRP78 and PERK and the translation of eukaryotes The expression of eIF2α, endoplasmic reticulum-derived transcription factor and transcription activator 4 (ATF4) mRNA were detected. The volume of cerebral infarction and the pathological changes of hippocampus were detected at 72 h after modeling. Results Compared with sham operation, the expression of GRP78, PERK protein and mRNA, eIF2α, chop and ATF4 mRNA in model group were significantly increased at each time point, and the volume of cerebral infarction was significantly increased (P <0.01) Compared with the model group, the expression of PERK, PERK, eIF2α, chop and ATF4 mRNA, the expression of GRP78 protein and mRNA in Yangyintongnao granule group were significantly increased, the volume of cerebral infarction was obviously Shrinkage (P <0.05 or P <0.01). Conclusion Yangyintongnao granule may alleviate cerebral ischemia-reperfusion injury by regulating the expression of endoplasmic reticulum-related factor in the hippocampus, inhibiting endoplasmic reticulum stress.