基于TGF-β1/Smad3信号通路探讨金合欢素对急性脑梗死大鼠神经功能的保护作用  

Protective Effect of Acacetin on Nervous Function of Rats with Acute Cerebral Infarction Based on TGF-β1/Smad3 Signal Pathway

作　　者：郑建君 杨霄敏 毛玲群[2] Zheng Jianjun;Yang Xiaomin;Mao Lingqun(Department of Neurology,Huangyan District Hospital of Traditional Chinese Medicine in Taizhou City,Zhejiang Taizhou 318020,China;Department of Neurology,Taizhou Central Hospital)

机构地区：[1]台州市黄岩区中医院神经内科,浙江台州318020 [2]台州市中心医院神经内科

出　　处：《中国药师》2020年第7期1350-1354,共5页China Pharmacist

摘　　要：目的:探讨金合欢素对急性脑梗死大鼠神经功能的保护作用及转化生长因子-β1(TGF-β1)/Smad家族成员3(Smad3)信号通路的影响。方法:100只SD大鼠随机分为5组:正常对照组、模型组、丁苯酞组(20.0 mg·kg^-1)、金合欢素低、高剂量组(40.0,80.0 mg·kg^-1),每组20只。除正常对照组外,其余各组建立急性脑梗死模型。建模成功后,丁苯酞组、金合欢素低、高剂量组给予相应药物灌胃,每天1次,持续给予7 d,正常对照组、模型组给予等体积的生理盐水。实验结束后,测定大鼠神经功能评分,HE染色观察大鼠脑组织结构病理改变,同时实时荧光定量逆转录聚合酶链反应(RT-PCR)法、蛋白质免疫印迹(Western Blot)法测定大鼠脑TGF-β1、Smad3 mRNA及蛋白表达水平。结果:与正常对照组比较,模型组逃避潜伏期时间、TGF-β1、Smad3 mRNA及蛋白表达水平显著升高,经过原平台位置次数、原平台象限停留时间显著降低(P<0.05);与模型组比较,丁苯酞组、金合欢素低、高剂量组逃避潜伏期时间、TGF-β1、Smad3 mRNA及蛋白表达水平显著降低,经过原平台位置次数、原平台象限停留时间显著升高(P<0.05),金合欢素各组呈剂量依赖性(P<0.05);金合欢素低剂量组与丁苯酞组比较差异有统计学意义(P<0.05)。模型组脑组织见大量坏死神经元,且神经细胞排列松散,细胞间隙增宽,呈缺血样病理改变,空泡样变性坏死数量较多;丁苯酞组和金合欢素高剂量组脑组织结构病理得到明显改善。结论:金合欢素对急性脑梗死大鼠表现出较强的神经保护作用;其机制可能与金合欢素通过抑制TGF-β1、Smad3 mRNA和蛋白的表达,进而抑制TGF-β1/Smad3信号通路有关。Objective:To investigate the protective effect of acacetin on nervous function of rats with acute cerebral infarction and its effect on transforming growth factor-β1(TGF-β1)/recombinant human Smad family member 3(Smad3)signaling pathway.Methods:Totally 100 SD rats were randomly divided into 5 groups:the normal control group,the model group,butylphthalide group(20.0 mg·kg^-1),and acacia low and high dose groups(40.0 and 80.0 mg·kg^-1)with 20 rats in each group.The models of acute cerebral infarction were established in butylphthalide group,and acaciatin low and high dose groups.After the successful modeling,butylphthalide group and acaciatin low and high dose groups were given the corresponding drug by gavage once a day for 7 days.The normal control group and the model group were given the same volume of saline.At the end of the test,the nerve function score of rats was measured,and the pathological changes of brain tissue structure of rats were observed by HE staining.At the same time,real time fluorescence quantitative reverse transcription polymerase chain reaction(RT-PCR)and Western immunoblotting(Western blotting)were used to determine brain TGF-β1 and Smad3 mRNA and protein expression levels in rats.Results:Compared with those in the normal control group,the time of avoiding incubation period,mRNA and protein expressions of TGF-β1 and Smad 3 in the model group were significantly increased,and the number of passing through the original platform position and the original platform quadrant residence time were significantly decreased(P<0.05).Compared with those in the model group,the time of avoiding incubation period,mRNA and protein expressions of TGF-β1 and Smad 3 in butylphthalide group,and acacia low and high dose groups were significantly decreased,the number of passing the original platform position and the original platform quadrant residence time were significantly increased(P<0.05).The effects of acacia groups were in a dose-dependent manner(P<0.05).The difference between acacia low dose group a

关 键 词：金合欢素 转化生长因子-β1/Smad家族成员3信号通路 急性脑梗死 神经功能 

分 类 号：R965.1[医药卫生—药理学]