Gualou Guizhi Granule(栝楼桂枝颗粒)Promotes Angiogenesis and Neurological Recovery by Improving the Expression of HIF-1α-NETRIN-1-UNC5B/VEGF Cascade after Cerebral Ischemic Injury in Rats
Objective:To investigate whether Gualou Guizhi Granule(栝楼桂枝颗粒)promotes angiogenesis and neurological recovery after cere-bral ischemic injury through HIF-1α-Netrin-1-UNC5B/VEGF pathway.Methods:Thirty-two SD rats were randomly selected to establish the middle cerebral artery occlusion and reperfusion model.After modeling,rats were randomly divided into model group and Gualou Guizhi Gran-ule 3.6 g/kg group,and 16 other rats were enrolled in control group.Rats were administrated with corresponding drugs or normal saline by gavage.Modified neurological severity score(mNSS),Ashworth score and CatWalk gait analysis were used to evaluate the neurological func-tion of rats in each group.Magnetic resonance imaging(MRI)was used to detect the cerebral infarct volume of rats.Immunohistochemistry and Western blot were used to detect the expression of angiogenesis and HIF-1α pathway related proteins in each group.Results:Compared with the control group,the mNSS and Ashworth scores were significantly increased,and the movement time and change of maximum speed of rats were significantly increased in model group(P<0.01).Large white cerebral infarct area was detected in rat brain,and the cerebral infarct volume was increased.The protein expression level of HIF-1αwas significantly increased,and the positive expression rate of CD34 in cerebral cortical tissue of the ischemia side was significantly increased(P<0.05).Compared with model group,the mNSS and Ashworth scores were significantly decreased in Gualou Guizhi Granule 3.6 g/kg group(P<0.05 or P<0.01),and the cerebral infarct volume and the movement time of rats was significantly decreased(P<0.01).The protein expressions of VEGFA,CD34,HIF-1α,NETRIN-1 and UNC5B were signifi-cantly up-regulated in Gualou Guizhi Granule 3.6 g/kg group(P<0.05 or P<0.01).Conclosion:Gualou Guizhi Granule can promote the angiogenesis and neurological function recovery after ischemic stroke,and its mechanism may be related to the activation of HIF-1α-NETRIN-1-UNC5B/VEGF signaling pathway.It will provide experimental basis for the clinical treatment of ischemic stroke.