Based on the pathophysiology of the brain,advance in angiogenesis induced by stroke,and evidences of Chinese-medicine-mediated angiogenesis,the possibility to study the stroke-treating mechanism of Chinese medicine in angiogenesis was discussed.And regarding our previous work on angiogenesis modulated by qi-tonifying and stasis-eliminating therapy following intracerebral hemorrhage,we proposed some questions,which should be taken into account in the further work.
目的通过观察益气活血法对脑出血大鼠脑内损伤区凝血酶敏感蛋白-1(thrombospondin-1,TSP-1)及其受体CD36表达的影响,初步探讨益气活血法治疗脑出血的机制。方法将155只SD大鼠随机分为正常组、假手术组、模型组、益气活血组、益气组和活血组;用Ⅶ型胶原酶诱导脑出血大鼠模型,再对相应的组分别灌服补阳还五汤及该方的益气药组和活血药组,在不同的时间点取脑组织并用免疫印迹(Western-blotting)分析鼠脑TSP-1及CD36的表达。结果正常组和假手术组不同时间点TSP-1和CD36表达无明显变化。模型组TSP-1在脑出血后4 d达高峰,CD36分别在脑出血后4、28 d达高峰。益气活血组1 d TSP-1表达低于模型组(P<0.01),4 d TSP-1和CD36表达均低于模型组(P<0.01),28 d CD36表达高于模型组(P<0.01)。结论益气活血法有可能通过影响脑出血后损伤区TSP-1及其受体CD36的表达,降低其对血管新生的抑制作用,促进新生血管成形、成熟和脑组织修复。
Objective:To investigate the effects and mechanism of qi-tonifying and stasis- eliminating(QTSE)therapy on the expression of vascular endothelial growth factor(VEGF)and its receptors Fit-1 and FIk-1 in the brains of intracerebral hemorrhagic(model)rats.Methods:One hundred and eighty Sprague-Dawley rats were randomly divided into six groups:the normal group (n=5),the sham-operative(SO)group(n=35),the model group(n=35),the QTSE group(n=35),the QT group(n=35)and the SE group(n=35).All the rats except those in the normal group and SO group were established into an intracerebral hemorrhage(ICH)model by intracerebral injection of collagenase typeⅦand the latter three were orally administered with Buyang Huanwu Decoction (补阳还五汤,a classical recipe for QTSE)or with some of its components for qi-tonification and for stasis-elimination,respectively.To the other three groups,normal saline solutions were given instead.Behavioral tests were carried out in the animals randomly chosen from each group on days 1, 2,4,7,14,21 and 28 after modeling.The expressions of VEGF,FIk-1 and Fit-1 were determined by immunohistochemistry and the number of vascular segments with positive expression in the injured brain area of the rats was calculated.Results:From day 7 onwards,the asymmetric forelimb use rate in the QTSE group recovered more significantly than that in the other model groups.In the model group,the expressions of VEGF,FIk-1 and Fit-1 appeared on day 1 and reached a peak on day 21, then weakened gradually.In the QTSE group,as compared with the other model groups,a higher level of VEGF expression was shown from day 7(P<0.01)and a higher level of Fit-1 expression was shown from the 7th day to the 21st day(P<0.01).Conclusion:QTSE therapy can up-regulate the expressions of VEGF and its receptors(FIk-1 and Fit-1)and improve the recovery of kinetic function in the ICH rats,which may be correlated with its action in modulating vascular regeneration to promote the reconstruction of microvascular networks in the damaged areas.
