参芎注射液对大鼠脑缺血再灌注后内质网应激相关分子X盒结合蛋白1表达的影响

目的 观察参芎注射液对大鼠脑缺血再灌注后脑内X盒结合蛋白1(X-box binding protein 1,XBP1)基因表达变化的影响,探讨其脑保护作用及机制.方法 144只雄性SD大鼠随机分为假手术组、生理盐水对照组和参芎组,采用线栓法制作大脑中动脉闭塞模型,参芎组大鼠在再灌注时腹腔注射参芎注射液33.3 ml/kg,生理盐水对照组腹腔注射等体积生理盐水.再灌注后6、12、24和72 h时处死动物,分别应用免疫组化染色和逆转录聚合酶链反应检测脑缺血区XBP1蛋白和mRNA表达,应用TUNEL法检测神经细胞凋亡.结果 再灌注后XBP1蛋白和mRNA水平均有升高,再灌注12 h达高峰;参芎组再灌注后6、12、24和72 h时,凋亡细胞数量和神经功能评分均低于生理盐水对照组(P均＜0.01),再灌注后6、12和24 h时,XBP1 mRNA水平也显著低于相应时间点的生理盐水对照组(P均＜0.01).结论 参芎注射液对脑缺血再灌注损伤诱导的内质网应激启动的XBP1通路有一定的抑制作用.

Effect of Shenxiong Injection on the expression of X-box binding protein 1 of endoplasmic reticulum stress following cerebral ischemia-reperfusion injury in rats

Objective To observe the effect of Shenxiong injection on the changes of brain X-box binding protein 1 (XBP1) gene expression following cerebral ischemia-reperfusion in rats and to investigate its neuroprotective effect and mechanisms. Methods One hundred forty-four male SD rats were randomly assigned to sham-operation, saline control and Shenxiong groups. A rat model of middle cerebral artery occlusion was induced using the suture method. Shenxiong injection 33.3 ml/kg was injected intraperitoneally during the reperfusion in the Shenxiong group. The same volume of saline was injected intraperitoneally in the saline control group. The animals were sacrificed at 6, 12, 24, and 72 hours after the reperfusion.Meanwhile, immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) were used respectively to detect the expressions of XBP1 protein and mRNA in the cerebral ischemic areas. TUNEL was used to detect neuronal apoptosis. Results The levels of XBP1 protein and mRNA increased after the reperfusion, and it reached the peak at 12 hours; both the numbers of apoptotic cells and neurological scores in the Shenxiong group were lower than those in the saline control group at 6, 12, 24, and 72 hours after the reperfusion (all P ＜0.01); the levels of XBP1 and mRNA at 6, 12, and 24 hours after the reperfusion were alsosignificantly lower than those in the saline control group (all P ＜ 0.01). Conclusions Shenxiong injection may have certain inhibition on the endoplasmic reticulum stress activated XBP1 pathway induced by cerebral ischemia-reperfusion.