注射用丹参多酚酸和血栓通注射液联合应用对局灶性脑缺血再灌注大鼠脑组织星形胶质细胞和小胶质细胞的影响及作用机制研究

目的研究注射用丹参多酚酸(SLI)和血栓通注射液(XST)合用对局灶性脑缺血再灌注损伤大鼠脑组织星形胶质细胞和小胶质细胞的影响及作用机制。方法 250~300 g雄性Wistar大鼠随机分为对照组、模型组、依达拉奉(EDI,6mg/kg)组、SLI(21 mg/kg)组、XST(100 mg/kg)组、SLI+XST组(1X1S,21 mg/kg+100 mg/kg),采用Longa法建立大脑中动脉栓塞脑缺血再灌注(MCAO/R)模型,缺血1.5 h、再灌注24 h后,尾iv给药,每天1次,连续给药3 d,检测体质量、神经功能评分及死亡率;免疫荧光法检测胶质纤维酸性蛋白(GFAP)和离子钙接头蛋白抗体(IBA-1)的变化;生物反应路径分析(IPA)构建和分析SLI和XST"成分-靶点-脑卒中"复杂网络。结果与模型组相比,1X1S能明显改善脑缺血再灌注大鼠的神经功能障碍,增加大鼠体质量,显著抑制缺血半暗带区域GFAP和IBA-1的表达(P0.01);IPA揭示了SLI和XST治疗脑卒中的相关作用机制。结论 SLI和XST合用对大鼠脑缺血再灌注损伤具有明显保护作用,其机制可能与抑制GFAP和IBA-1的表达及高迁移率族蛋白通路和白细胞介素-8(IL-8)信号通路等有关。

Effect and mechanism of Salvianolate Lyophilized Injection combined with Xueshuantong Injection on expression of astrocytes and microglia on focal cerebral ischemia-reperfusion injury in rats

Objective To investigate the effect of Salvianolate Lyophilized Injection (SLI) combined with Xueshuantong Injection (XST) on expression of astrocytes and microglia in cerebral ischemia-reperfusion injury rats. Methods The Wistar rats (250-300 g, male) were randomly divided into six groups:control group, model group, Edaravone group (6 mg/kg, EDI), SLI group (21 mg/kg), XST group (100 mg/kg), and SLI+XST group (1X1S, 21 mg/kg and 100 mg/kg). Rat model of cerebral ischemia-reperfusion injury was created by the middle cerebral artery occlusion (MCAO) by longa method. Drugs were administered tail intravenous injection once a day for 3 d starting from 24 h after reperfusion. The body weight, neurological deficit scores and survival percentage were observed in 3 d after the cerebral ischemia. The expression of GFAP and IBA-1 was determined at 3 d by immunofluorescence. The complicated compound-target-stroke network of SLI and XST was constructed and analyzed by IPA. Results Compared with the model group, 1X1S could significantly improve the neurological dysfunction, increase the body weight, and inhibit the expression of GFAP and IBA-1 in ischemic penumbra (P<0.01), IPA reveals the molecular mechanism of SLI and XST in the active ingredient and related targets. Conclusion 1X1S has significant protection on cerebral ischemia reperfusion injury in rats, which may be related to the inhibition of the expression of GFAP and IBA-1 and high mobility group box-1 signaling and Interleukine-8 signaling.