The Effect Of Yiqi Huoxue Therapy On Expression Of VEGF And Its Receptors Flt-1, Flk-1 In Intracerebral Hemorrhagic Rat Brains

Backgroud and object:Cerebrovascular disease has a up-rising tendecy and has become one of the most serious disease,paralleling with coronary atherosclerotic heart disease and cancer.Intracerebral hemorrhage(ICH)is one of such cerebrovascular disease with the characteristics of acute Pathogenesis,complex complications,high rate of mortality and disability,what' more,its younger mortalitiy rate becomes more and more notable.ICH belongs to the category of stroke in traditional chinese medicine(TCM).The insight about etiology and pathology of stroke in TCM becomes more and more meticulous after thousands of specialists' constant attempt.A famous doctor in qing dynasty,Wang Qingren posed that Qixu Xueyu was one of the most impotant pathology about stroke.Buyang Huanwu Decoction which was invented by Wang Qingren was the classic prescription owning the characteristic of Yiqi Huoxue(YQHX)therapy.This prescription remains effective in treating stroke nowadays.Today,the exploration in YQHX therapy and Buyang Huanwu Decoction grows more and more intensive and the impact of TCM pharmacology on pathophysiology of ICH becomes the hot topic.Clinic research demonstrated that YQHX therapy combined with hematoma clearance by surgical minimally invasion or western medicine regular treat has a more notable effect than surgery only or western medicine regular treat alone,reflecting the treat advantage of TCM.Modern researches have proved YQHX therapy has the notable effect of eliminating symptoms after ICH,improving the circulation in the brain,promoting evacuation of the hematoma, inhibiting edema and inflammatory reaction in brain tissue around hemorrhagic focus,relieving brain tissue's compression and damage caused by hematoma,promoting the recovery of the nervous system and reducing disability and mortality.The most important pathology change after ICH was damage of microvessel system in hematoma zone and secondry damage of ischemic and anoxemia in semidarkness zone around hematoma.Vascular endothelial growth factor(VEGF)is the most important angiogenesis factor.It can accelerate accrementition of endothelial cells and protect vascular endothelial cells,improve micro-circulation,increase oxygen supply in damaged brain tissue, reduce the mumber of apoptosis and dead neurons,and as a result,lessen ischemic brain damage by combined with its receptor,fms-like tyrosine kinase-1(Flt-1)and fetal liver kinase-1(Flk-1).So,we assume that Yiqi Huoxue therapy can effect the expression of VEGF and its receptor Flt-1 and Flk-1 and play the therapeutic action role on ICH.Accordingly,the purpose of our present work is to evaluate whether the expression of VEGF and its receptors Flt-1 and Flk-1 is altered in rat brains with collagenase-induced ICH,and to investigate effects of the YQHX therapy on expression of VEGF and its receptors Flt-1 and Flk-1 following ICH,to study the mechanism of YQHX therapy on reconstruction of capillary vessel system in the hematoma area after ICH initially.Methods:155 Sprague-Dawley rats were randomly divided into six groups including normal control group(n=5),sham control group(n=30), ICH model control group(n=30),Yiqi-treated group(n=30), Huoxue-treated group(n=30)and YQHX-treated group(n=30).By injecting collagenase typeⅦstereotaxically into right pallidum,ICH model was made.Yiq,HuoXue and YQHX-treated group were respectively administered with YiQi decoction,HuoXue decoction and Buyang Huanwu decoction.The expression of VEGF,Flt-1 and Flk-1 was assayed by western blot at day 1,4,7,14,21 and 28 after the onset.Results:There were no significant expression of VEGF,Flt-1 and Flk-1 in rat brains of normal or sham group during the experiment;In model group,the expressions of VEGF,Flt-1 and Flk-1 appeared at ld, peaked at 21d,and then weakened gradually;The expressions of VEGF,Flt-1 and Flk-1 in YQHX-treated group were significantly higher than those in the other groups from 7d to 21d(p＜0.01),and the expression of VEGF and Flk-1 in YQHX-treated group reached peak at 14d,but the expression of Flt-1 reached peak at 21d(p＜0.01).Conclusion:1.ICH could lead to the up regulation of the expression of VEGF and its receptors Flt-1 and Flk-1 in intracerebral hemorrhagic rats brain.2.YQHX therapy has a positive effect on the promotion to the expression of VEGF,Flt-1 and Flk-1 in the rat brain of ICH,YQHX therapy may promote angiogenesis,accelerate the absorption of hematoma and promote the neurofunctional recovery of ICH rat.