小蘖碱对异丙肾上腺素诱导大鼠心肌梗死的保护作用  

Protective Effect of Berberine on Isoprenaline-induced Myocardial Infarction in Rats

作　　者：朱舜明[1] 张荣怀[1] 张学军[1] 祝领[1] 安慧仙 王瑞 曾广伟 ZHU Shun-ming;ZHANG Rong-huai;ZHANG Xue-jun;ZHU Ling;AN Hui-xian;WANG Rui;ZENG Guang-wei(st Department of Cardiology,Shaanxi Provincial People's Hospital,Xi'an,Shaanxi,710068,China;Department of Cardiology,The Second Affiliated Hospital of Air Force Medical University,Xi'an,Shaanxi,710038,China;Department of Cardiology,Xi'an International Medical Center Hospital,Xi'an,Shaanxi,710100,China)

机构地区：[1]陕西省人民医院心内一科,陕西西安710068 [2]空军军医大学第二附属医院心内科,陕西西安710038 [3]西安国际医学中心心内科,陕西西安710100

出　　处：《现代生物医学进展》2020年第19期3627-3633,共7页Progress in Modern Biomedicine

基　　金：国家自然科学基金青年基金项目(81700401);陕西省重点研发计划项目(2018SF-085)。

摘　　要：目的:揭示小蘖碱(BER)对异丙肾上腺素(ISO)诱导大鼠心肌梗死的保护作用及机制。方法:将100只SD大鼠随机分为5组(n=20):对照组、ISO组、ISO+10BER(BER 10 mg/kg/d)、ISO+20BER(BER 20 mg/kg/d)和ISO+50BER(BER 50 mg/kg/d)。给药组大鼠按照指定的剂量灌胃BER,对照组和ISO组灌胃等体积无菌水,共灌胃2周。然后,除对照组之外,其他组大鼠皮下注射ISO(5 mg/kg/d),对照组皮下注射等体积的0.9%无菌盐水,连续3 d。通过超声心动图检查大鼠的EF、FS、LVEDD和LVESD;苏木精和伊红(HE)染色评价心肌组织形态学;Masson三色染色用于评估心脏的间质纤维化;2,3,5-氯化三苯基四氮唑(TTC)法检测心肌梗死体积。Western blot检测心肌组织中collagen Ⅰ、collagen Ⅲ、TGF-β1、TNF-α、Smad3、p-Smad3、NF-κB、α-SMA、Nrf2、HO-1、Bcl-2、Bax和caspase-3的表达。免疫组化评估间隙连接蛋白43(Cx43)的表达。使用试剂盒检测血清SOD、CAT和MDA表达水平。结果:与ISO组相比,BER预处理组大鼠的心肌梗死体积和LVEDD和LVESD显著降低,而EF和FS显著升高(P<0.05)。BER预处理组大鼠的纤维化标志物(collagen Ⅰ、collagen Ⅲ和α-SMA)表达水平与ISO组相比显著下调(P<0.05)。与ISO组相比,BER预处理组大鼠的TGF-β1/Smad3信号通路和炎症因子(TNF-α和NF-κB)被抑制。BER预处理组大鼠的Cx43阳性染色评分显著高于ISO组(P<0.05)。与ISO组相比,BER预处理组大鼠的促凋亡蛋白(Bax和caspase-3)被下调,而抗凋亡蛋白Bcl-2被上调(P<0.05)。与ISO组相比,BER预处理组大鼠的MDA水平显著降低,而SOD和CAT显著升高(P<0.05)。BER预处理组大鼠的Nrf2和HO-1水平显著高于ISO组(P<0.05)。结论:在异丙肾上腺素诱导的心肌梗死大鼠模型中,小檗碱预处理可通过抑制心脏纤维化、炎症反应、心肌细胞凋亡和氧化应激损伤来减少心肌梗死体积并改善心脏功能。Objective:To reveal the protective effect and mechanism of berberine(BER)on isoprenaline(ISO)-induced myocardial infarction in rats.Methods:100 SD rats were randomly divided into 5 groups(n=20):control group,ISO group,ISO+10BER(BER 10 mg/kg/d),ISO+20BER(BER 20 mg/kg/d)and ISO+50BER(BER 50 mg/kg/d).The rats in the administration group were orally administered BER at the prescribed dose,and the control group and the ISO group were orally administered with an equal volume of sterile water for 2 weeks.Then,except for the control group,rats in the other groups were subcutaneously injected with ISO(5 mg/kg/d),and the control group was subcutaneously injected with an equal volume of 0.9%sterile saline for 3 consecutive days.The EF,FS,LVEDD and LVESD of the rats were examined by echocardiography.Hematoxylin and eosin(HE)staining was used to evaluated myocardial histomorphology.Masson trichrome staining was used to assess cardiac interstitial fibrosis.The volume of myocardial infarction was measured by 2,3,5-triphenyltetrazolium chloride(TTC)method.Western blot was used to detect the protein expression of collagen I,collagenⅢ,TGF-β1,TNF-α,Smad3,p-Smad3,NF-κB,α-SMA,Nrf2,HO-1,Bcl-2,Bax and caspase-3.Immunohistochemistry was used to assessed gap junction protein 43(Cx43)expression.Serum SOD,CAT and MDA levels were measured using a commercial kit.Results:Compared with the ISO group,the myocardial infarction volume and LVEDD and LVESD of the BER pretreatment group rats were sig-nificantly reduced,while EF and FS were significantly increased(P<0.05).Fibrosis markers(collagen I,collagenⅢ,andα-SMA)in the BER pretreatment group rats were significantly down-regulated compared to the ISO group(P<0.05).Compared with the ISO group,the TGF-β1/Smad3 signaling pathway and inflammatory factors(TNF-αand NF-κB)in the BER pretreatment group rats were inhibited(P<0.05).The Cx43 positive staining score of the BER pretreatment group rats was significantly higher than that of the ISO group(P<0.05).Compared with the ISO group,the pro-

关 键 词：小蘖碱 心肌梗死 异丙肾上腺素 心脏纤维化 炎症 细胞凋亡 氧化应激 

分 类 号：R-33[医药卫生] R542.22