养阴通脑颗粒对脑缺血再灌注损伤大鼠海马内质网应激的影响

Impact of Yangyin Tongnao Keli(养阴通脑颗粒) on Hippocampus Endoplasmic Reticulum Stress in Rats with Cerebral Ischemia Reperfusion Injury

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 explore the possible mechanism of Yangyin Tongnao Keli（ 养阴通脑颗粒） decreasing cerebral ischemia reperfusion injury. Methods Totally 162 Sprague Dawley（ SD） rats were randomized into sham operation group,model group and Yangyin Tongnao Keli group,with 54 rats in each group. The model group and the Yangyin Tongnao Keli group were established cerebral ischemia reperfusion injury models by middle cerebral artery focal embolism operation. The Yangyin Tongnao Keli group was given Yangyin Tongnao Keli 0. 5 g/kg by gavage every12 hours. The sham operation group and the model group were given equivalent normal saline. After 12,24,48,and72 hours of modeling,neurological deficit score,glucose regulated protein 78（ GRP78） in CA1 area of hippocampus,protein kinase R-like ER kinase（ PERK） and the expressions of mRNA,as well as the mRNA expressions of eukaryotic translation initiation factor 2α（ e IF2α）,endoplasmic reticulum derived transcription factor CCAAT/enhancer binding protein homologous protein（ chop） and activating transcription factor 4（ ATF4） were observed. The volume of cerebral infarction and the pathological changes of hippocampus in brain tissue were detected after 72 hours of modeling. Results Compared with the sham operation group,neurological deficit score,GRP78,PERK protein and mRNA expressions,as well as the expressions of e IF2α,chop and ATF4 at each time point in the model group increased. The volume of cerebral infarction increased（ P〈0. 01）. Compared with the model group,neurological deficit score,PERK protein and the mRNA expressions of PERK,e IF2α,chop and ATF4 decreased. GRP78 protein and the expression of mRNA increased. The volume of cerebral infarction decreased（ P〈0. 05 or P〈0. 01）.Conclusion Yangyin Tongnao Keli might inhibit endoplasmic reticulum stress by regulating the expressions of hippocampus endoplasmic reticulum related factors to decrease cerebral ischemia reperfusion injury.