小檗胺在严重烧伤大鼠心肌损伤中的保护作用  

Protective effects of berbamine on myocardial injury in severely burned rats

作　　者：张彬[1,2] 翟蒙恩 段维勋 刘金成 金振晓 俞世强 Zhang Bin;Zhai Mengen;Duan Weixun;Liu Jincheng;Jin Zhenxiao;Yu Shiqiang(Department of Cardiovascular Surgery,Xijing Hospital,Air Force Medical University,Shaanxi Xi'an 710032,China)

机构地区：[1]中国人民解放军陆军第954医院外科,西藏山南856100 [2]空军军医大学西京医院心血管外科,陕西西安710032

出　　处：《中国体外循环杂志》2022年第4期240-247,252,共9页Chinese Journal of Extracorporeal Circulation

基　　金：国家自然科学基金青年科学基金项目(82000373);西京医院学科助推计划(XJZT19MJ25)。

摘　　要：目的探究小檗胺(BBM)对严重烧伤大鼠心肌损伤的保护作用及其分子机制。方法采用背部烫伤法构建大鼠烧伤模型。实验分组如下:假烧伤组(Sham)、单纯BBM处理组(BBM)、烧伤组(Burn)和烧伤+BBM处理组(Burn+BBM)。待烧伤12 h后,心导管检测大鼠心脏功能,HE染色观察心肌组织形态结构变化,试剂盒检测心肌组织氧化应激和炎症反应水平,末端标记法染色检测细胞凋亡程度,蛋白印迹法检测线粒体去乙酰化酶(SIRT3)通路蛋白表达情况。结果与Sham组比较,Burn组大鼠左室收缩压与左室压最大增减速率(±dp/dt_(max))值均显著降低,血清肌钙蛋白T及肌酸激酶同工酶水平明显上升;血清白介素(IL)-1β、IL-6和肿瘤坏死因子-α含量及心肌组织髓过氧化物酶活性显著升高;心肌组织丙二醛含量及活性氧产量明显增多,超氧化物歧化酶活性显著下降;心肌凋亡细胞及凋亡蛋白切割型半胱氨酸天冬氨酸蛋白水解酶-3(cleaved caspase-3)表达显著增多;并且心肌组织SIRT3信号表达显著减弱(均P<0.05)。与Burn组比较,Burn+BBM组大鼠心脏收缩功能显著改善,血清炎性因子水平显著降低,心肌组织氧化应激程度显著下调,心肌细胞凋亡被显著抑制,同时心肌组织SIRT3信号表达显著增强(均P<0.05)。结论BBM通过激活心肌SIRT3信号,增强心肌组织抗氧化应激损伤和抗炎症反应的能力,进而减轻严重烧伤大鼠心肌损伤。Objective To investigate the protective effects of berbamine(BBM)on early myocardial injury in severely burned rats and its molecular mechanism.Methods The burn model was established by subjecting rats to third degree burns on the back.The experimental groups were as follows:Sham,BBM,Burn and Burn+BBM groups.Twelve hours after the burn treatment,cardiac func⁃tion of rats was detected by cardiac catheters,morphological and structural changes of myocardial tissue were observed by HE staining,oxidative stress and inflammatory response of myocardial tissue were detected by special kits,cell apoptosis was observed by TUNEL staining,and protein expressions of SIRT3 pathway were detected by Western blot.Results Compared with the Sham group,LVSP and±dp/dt_(max) values were significantly decreased in the Burn group,while serum cTnT and CKMB levels were significantly increased.The contents of IL-1β,IL-6 and TNF-αin serum and the activity of MPO in myocardial tissue were significantly elevated.MDA con⁃tent and ROS(reactive oxygen species)production were largely increased,while SOD activity was markedly decreased.The apoptosis of cardiomyocytes and expression of cleaved caspase 3 were remarkably increased.Additionally,the expression and deacetylation activi⁃ty of SIRT3 were significantly decreased in the Burn group(all P<0.05).Compared with the Burn group,the systolic function was sig⁃nificantly improved,the levels of serum inflammatory factors were significantly decreased,the oxidative stress injury of myocardial tis⁃sue was significantly alleviated,the apoptosis of cardiomyocytes was significantly inhibited,and the expression of SIRT3 signaling was significantly enhanced in the Burn+BBM group(all P<0.05).Conclusion BBM can play anti-oxidative stress and anti-inflammatory effects by activating SIRT3 signaling,thus alleviating early myocardial damage in severely burned rats.

关 键 词：严重烧伤 心肌损伤 小檗胺 炎症 氧化应激 沉默信息调控因子3 

分 类 号：R285.5[医药卫生—中药学]