Studics On Angiogenic Mechanisms And Protective Effect Against Cerebral Ischemia Of Buyang Huanwu Decoction

Backgrounds:With the gradually increasing of the aging population, the morbidity and mortality of cerebral infartion is vastly increased in recent years, which urgently requires us to prevent and treat the occurrence and development of cerebral infarction. Drug therapy is one of the most important ways in the clinical therapeutics of cerebral infartion, especially for patients who can not be treated by thrombolysis. In china, Buyang Huanwu decoction(BYHWD) have been used for the prevention and treatment of cerebral infartion, but the active componets and mechanisms of action are still unclear. With the deepening research on the phenomenon of angiogenesis after cerebral infarction, using drugs to promote blood vessel formation in order to increase the blood supply in penumbra area, that is, therapeutic angiogenesis, plays an important role in promoting blood circulation, protecting neurons and improving neurological function after cerebral ischemia. It is believed that angiogenesis may provide a new way for the treatment of cerebral infarction. Therefore, studies on therapeutic angiogenesis induced by BYHWD may play important roles in the treatment of cerebral infartion.Objectives:This paper intends to observe the effects and mechanisms of BYHWD on angiogenesis after cerebral infarction. (1) The effects of BYHWD on neurological function and angiogenesis after cerebral infarction in middle cerebral artery occlusion(MCAO) rats.(2) The angiogenic effects of BYHWD in hydrogen peroxide(H2O2)-induced human umbilical vein endothelial cells(HUVECs).(3) The angiogenic mechanisms of BYHWD in H2O2-induced HUVECs.Methods:Firstly, by detecting neurological deficits, cerebral infarct and atrophy volume, spatial memory function, cerebral blood flow(CBF) and microvascular density(MVD), we observed the effects of BYHWD on neurological function and angiogenesis after cerebral infarction in MCAO rats. Secondly, by establishment of H2O2-induced HUVECs cell injury model, we detected cell viability, apoptosis, and vascular tube formation to observe the effects of BYHWD on angiogenesis, Finally, by detecting intracellular ROS generation and Nox4protein expression in HaCVinduced HUVECs, we clarify the angiogenic mechanisms of BYHWD in H2O2-induced HUVECs.Results:Part â… BYHWD significantly improves neurological function in rats, including neurological deficits and spatial learning and memory; significantly reduces cerebral infarct and atrophy volume, and significantly increases CBF and MVD in the ischemic area. Part â…¡BYHWD significantly increases cell viability, inhibit apoptosis and induces vascular tube formation in H2O2-induced HUVECs in a concentration-dependent manner. Part â…¢BYHWD significantly decreases intracellular ROS generation, and reduces NADPH oxidase(Nox) activity and Nox4protein expression in H2O2-induced HUVECs in a concentration-dependent manner.Conclusions:Our study shows that BYHWD promotes neurological function recovery by increasing angiogenesis and CBF in penumbra area after cerebral infarction in vivo, and in vitro, BYHWD improves angiogenesis in H2O2-induced HUVECs, suggesting the angiogenic mechanisms through downregulation of Nox4, which in turn results in the reduction of ROS generation.