环维黄杨星D对高血压大鼠脑缺血GAP-43 mRNA表达与细胞损伤的影响

目的观察中药单体环维黄杨星D(CVB-D)对易卒中型肾血管性高血压大鼠(RHRSP)脑缺血再灌注不同时间脑组织生长相关蛋白-43(GAP-43)mRNA表达与细胞超微结构损伤的影响。方法采用环形银夹使SD大鼠的双侧肾动脉狭窄,制成RHRSP,再用线栓法制成一侧大脑中动脉闭塞(MCAO)模型。用原位杂交等方法观察CVB-D对脑缺血2h后复流1d、7d、14d、30d不同时间点大鼠脑组织GAP-43mRNA表达、水含量、梗死面积百分率、行为学评分及细胞超微结构的干预作用。结果脑缺血2h复流后1d缺血区周围及海马可见GAP-43mRNA表达,7d明显增多至高峰,14d开始下降,30d时则明显减少,CVB-D治疗组在上述区域各时间点较对照组显著增加。脑缺血再灌注7d后,治疗组较对照组大鼠脑水含量及梗死面积显著降低,受损脑组织神经元和血管壁的超微结构亦明显改善。结论CVB-D对RHRSP缺血性脑细胞损伤有一定保护作用,其促进轴突的再生可能与上调脑组织GAP-43mRNA表达有关。

Effects of CVB-D on GAP-43 mRNA expression and cell injury in hypetensive rats with cerebral ischemia/reperfusion injury

Objective To observe the effects of cyclovirobuxine-D (CVB-D) on the expression of GAP-43 mRNA during the different time of cerebral ischemia and reperfusion and the changes of cell ultrastructure in cerebral tissue of stroke-prone renovascular hypertensive rats (RHRSP). Methods RHRSP models were established by bilaterally narrowing the renal artery with silver loop clips in rats and then the middle cerebral artery occlusion (MCAO) were created by thread occlusion method in the RHRSP models. Two-hour ischemia later, the expression of GAP-43 mRNA in the rat cerebral tissue was detected with in situ hybridization at day 1, 7, 14 and 30 of reperfusion for observing the effects of the CVB-D on the expression of GAP-43 mRNA, water content, infarct are, behavior scores and cell ultrastructure. Results The expression of GAP-43 mRNA was found in the ischemic area and the parahippocampal area after 2-hour reperfusion. It was increased significantly and up to the maximum after 7-day reperfusion, decreased after 14-day, and reduced markedly after 30-day. The CVB-D treatment group was obviously higher than the control group in the GAP-43 mRNA expression at different time points. Compared with the control group, the water content and the infarct area were obviously reduced after 2-hour cerebral ischemia and 7-day reperfusion. The injured cerebral neuron and the cell ultrastructure in blood vessel wall were repaired obviously. Conclusion CVB-D can protect the RHRSP rats from the ischemic cerebral damage more or less. Perhaps, the mechanism of the regeneration of axon is related with the increased expression of GAP-43 mRNA.