丹参酮对脑缺血再灌注大鼠梗死脑组织中血管生成的影响OA

Aim:To investigate the effect of tanshinone on angiogenesis in infarcted brain tissue of rats with cerebral is-chemia-reperfusion injury and its possible mechanisms.Methods:Sixty SD rats were randomly divided into 4 groups:sham group,middle cerebral artery occlusion-reperfusion(MCAO/R)group,tanshinone group,and tanshinone+miR group,with 15 rats in each group.Except for the sham group,the other 3 groups were established the MCAO/R model using suture-oc-cluded method.The tanshinone+miR group received intraventricular injection of AAV virus carrying miR-499-5p 1 hour before MCAO/R operation.The tanshinone group and tanshinone+miR group were administered tanshinone intraperitoneal-ly at a dose of 10 mg/(kg·d)after MCAO/R operation,the sham group and MCAO/R group received equal volumes of normal saline,once daily for 7 days.Neurological deficits were assessed using a double-blind scoring method.After euthana-sia,the brains were harvested for TTC staining to analyze infarcted area,CD31 immunofluorescence staining to evaluate an-giogenesis in infarcted tissues,RT-qPCR to detect miR-499-5p expression,and Western blot to measure the expression of hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)in infarcted tissues.Results:Com-pared with the sham group,the MCAO/R group exhibited enhanced neurologic deficit scores,increased expression of miR-499-5p,HIF-1α,and VEGF,and a reduced percentage of CD31-positive areas(P<0.05).Compared with the MCAO/R group,the tanshinone group showed decreased cerebral infarcted area and neurologic deficit scores,an increased percentage of CD31-positive areas,reduced expression of miR-499-5p,and enhanced expression of HIF-1α and VEGF protein(P<0.05).The tanshinone+miR group reversed the aforementioned indicators compared with the tanshinone group(P<0.05).Conclusion:Tanshinone may promote angiogenesis in ischemia-reperfusion brain injury tissues by regulating miR-499-5p/HIF-1α/VEGF signaling pathway.