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作 者:王晓 刘博[1] 张译心 王鑫[1] 周赫 纪凤兰[1] 丁涛[1] 温富春[1] 徐惠波[1] WANG Xiao;LIU Bo;ZHANG Yi-xin;WANG Xin;ZHOU He;JI Feng-lan;DING Tao;WEN Fu-chun;XU Hui-bo(Jilin Academy of Chinese Medical Sciences,Changchun 130012;School of Pharmacy,Changchun University of Chinese Medicine,Changchun 130117)
机构地区:[1]吉林省中医药科学院,长春130012 [2]长春中医药大学药学院,长春130117
出 处:《中南药学》2021年第6期1092-1097,共6页Central South Pharmacy
基 金:国家重大新药创制专项(No.2018ZX09711001-009-005);吉林省科技发展计划项目(No.20170311012YY)。
摘 要:目的明确黄连总生物碱与三七总皂苷组合物(简称HS组合物)对糖尿病心肌缺血再灌注损伤的治疗效果,初步探讨其作用机制。方法选用Wistar大鼠,以链脲佐菌素注射结合冠脉结扎制备糖尿病心肌缺血再灌注损伤模型。将大鼠随机分为对照组、模型组、二甲双胍组、HS组合物组,检测大鼠血清胰岛素、血糖、糖耐量、SOD、MDA及CK-MB水平;HE染色观察大鼠胰腺与心肌组织病理变化;Western Blot检测大鼠心肌组织NOX2、NOX4、NLRP3、IL-1β、Caspase-1、Bax、Caspase-3与Bcl-2蛋白表达水平。结果HS组合物能降低糖尿病心肌缺血再灌注损伤大鼠血糖,提高胰岛素水平(P<0.001),改善大鼠口服糖耐量、氧化应激及心肌酶变化,降低大鼠心肌NOX2、NOX4、NLRP3、Bax与Caspase-3蛋白的表达,升高Bcl-2蛋白的表达,减轻大鼠胰腺组织与心肌组织损伤。结论HS组合物能通过降低血糖、提高胰岛素水平,下调NOX2、NOX4以及NLRP3蛋白的表达,抑制氧化应激与炎症反应,从而改善心肌细胞凋亡,减轻糖尿病心肌缺血再灌注引起的心肌损伤。Objective To determine the therapeutic effect of rhizoma coptidis total alkaloids and panax notoginseng saponins(HS compound)on diabetic myocardial ischemia-reperfusion injury and to explore the mechanism of action.Methods Wistar rats were selected to establish diabetic myocardial ischemia reperfusion injury model by streptozotocin injection combined with coronary artery ligation.The rats were randomly divided into a control group,a model group,a metformin group and an HS compound group.The levels of serum insulin,blood glucose,glucose tolerance,SOD,MDA and CK-MB were detected.The pathological changes of pancreatic and myocardial tissues in the rats were observed by HE staining.The expression levels of NOX2,NOX4,NLRP3,IL-1β,Caspase-1,Bax,Caspase-3 and Bcl-2 in the myocardial tissues of the rats were detected by Western blot.Results HS compound reduced the blood glucose and increased the insulin level in the diabetic rats with myocardial ischemia-reperfusion injury.The expressions of NOX2,NOX4,NLRP3,Bax and Caspase-3 in the rat myocardium were decreased.The expression of Bcl-2 protein was increased.And the injury of pancreatic tissue and myocardial tissue in the rats was reduced.Conclusion HS compound can inhibit the oxidative stress and inflammatory response by reducing the blood glucose,increasing the insulin level,and down-regulating NOX2,NOX4 and NLRP3 protein expression.It can also reduce the myocardial apoptosis and myocardial injury caused by diabetic myocardial ischemia reperfusion.
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