目的 研究銀杏內(nèi)酯注射液（Ginkgolide Injection，GI）作用于大鼠腦缺血再灌注損傷的治療時(shí)間窗及對(duì)凋亡信號(hào)通路的影響。方法 采用Longa法制備大鼠大腦中動(dòng)脈短暫阻塞再灌注（tMCAO）模型，（1）分別于再灌后1、3、6、9 h ip首次給予GI （2.5 mg/kg），每天給藥2次，連續(xù)給藥3 d，通過神經(jīng)功能評(píng)分、腦梗死體積及腦組織含水量評(píng)價(jià)動(dòng)物缺血損傷程度。（2）于再灌注后1 h ip給予GI （2.5 mg/kg），每天給藥2次，連續(xù)給藥3 d，分別于再灌注后24、72 h取腦檢測(cè)缺血半影區(qū)p53、Bax、Bcl-2、Caspase 3蛋白表達(dá)水平。結(jié)果 與模型組比較，（1）再灌注后1、3 h給予GI能顯著降低神經(jīng)功能評(píng)分、減少腦梗死體積與腦組織含水量（P<0.05、0.01），6、9 h給藥大鼠腦損傷未見明顯改善。（2）于再灌注后1 h給予GI顯著抑制p53、Bax、Caspase 3蛋白表達(dá)，上調(diào)Bcl-2蛋白表達(dá)（P<0.05）。結(jié)論 GI對(duì)tMCAO模型大鼠的有效治療時(shí)間在缺血再灌注后3 h內(nèi)；其可能的作用機(jī)制涉及抑制凋亡信號(hào)通路的激活。

Objective To investigate the effects of Ginkgolide Injection (GI) on the therapeutic time window of cerebral ischemia-reperfusion and its apoptosis signaling pathway in rats.Methods A transcient middle cerebral artery occlusion (tMCAO) model was established using Longa's method. In the first section of the study, GI (2.5 mg/kg) was ip administrated respectively at 1, 3, 6, and 9 h post reperfusion, two times a day for three days continuously. The degree of cerebral ischemia injury in model rats was assessed according to the extent of neurologic status, infarction volume, and water content in brain. The second section of the study was started with the dose of GI (2.5 mg/kg) to the tMCAO rats at 1 h post reperfusion, two times a day for three days continuously. Then p53, Bax, Bcl-2, and Caspase 3 in penumbra were measured with Western blotting at 24 h and 72 h post reperfusion, respectively.Results Compared with model group, the neurological deficit, infarction volume as well as edema were significantly improved in the 1 and 3 h GI treated group (P < 0.05 and 0.01), and the brain damage of rats in the 6 and 9 h GI treated group were not significantly improved. The p53, Bax, and Caspase 3 were significantly down-regulated and the expression of Bcl-2 was significantly increased by GI administration both at 24 h and 72 h after reperfusion (P < 0.05).Conclusion The therapeutic window of GI for transient focal cerebral ischemic injury lasts for at least 3 h, and inhibition of the apoptosis activation was involed in GI protective mechanisms.