首页|栝楼桂枝颗粒通过HIF-1α-Netrin-1-UNC5B/VEGF促进大鼠脑缺血后血管生成和神经功能恢复的研究

栝楼桂枝颗粒通过HIF-1α-Netrin-1-UNC5B/VEGF促进大鼠脑缺血后血管生成和神经功能恢复的研究

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目的:探讨栝楼桂枝颗粒是否通过HIF-1α-Netrin-1-UNC5B/VEGF促进脑缺血后血管生成和神经功能恢复.方法:随机选取32只SD大鼠建立大脑中动脉闭塞再灌注损伤模型,造模成功后分为模型对照组、栝楼桂枝颗粒3.6 g/kg组,另设16只假手术对照组.各组灌胃给予相应药物或生理盐水,采用改良神经功能缺损(mNSS)评分、肌张力测评试验及Cat Walk步态分析系统评价各组大鼠神经功能恢复情况;采用MRI检测各组大鼠脑梗死面积,计算脑梗死率;采用免疫组化法、蛋白免疫印迹法(West-em blot)检测各组大鼠促血管生成及HIF-1α通路相关蛋白的表达.结果:与假手术对照组比较,模型对照组mNSS评分和肌张力评分均显著升高,运动时间和最大速率变化均显著升高(P<0.01),大鼠大脑检测出大片白色梗死区域,脑梗死面积显著增加;缺氧诱导因子(HIF-1α)蛋白表达明显升高,大鼠缺血侧大脑皮层组织中白细胞分化抗原(CD34)阳性表达率明显升高(P<0.05);与模型对照组比较,栝楼桂枝颗粒3.6 g/kg组大鼠神经行为学评分、肌张力明显降低(P<0.05或P<0.01),脑梗死率显著减少,大鼠运动时间显著降低(P<0.01);血管生成相关蛋白VEGFA、CD34蛋白表达明显上调(P<0.05或P<0.01),HIF-1α、神经导向因子-1蛋白(NETRIN-1)、神经导向因子受体(UNC5B)蛋白表达明显上调(P<0.05或P<0.01).结论:栝楼桂枝颗粒能够促进缺血性脑中风后的血管生成和神经功能恢复,其作用机制可能与激活HIF-1α-NETRIN-1-UNC5B/VEGF信号通路有关.
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.

Gualou Guizhi Granules(栝楼桂枝颗粒)Cerebral ischemia reperfusion injuryHypoxia inducible factorAngiogenesisNE-TRIN-1UNC5B

张玉琴、李亚男、冯怡、陈雯婷、罗书萍、南丽红

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福建中医药大学药学院,福州 350122

栝楼桂枝颗粒 脑缺血再灌注损伤 缺氧诱导因子 血管生成 神经导向因子-1蛋白 神经导向因子受体

2024

中药药理与临床
中国药理学会 四川省中医药科学院

中药药理与临床

北大核心
影响因子:0.996
ISSN:1001-859X
年,卷(期):2024.40(7)