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作 者:张玲 孙媛 高春华 隋海娟 于海英 杨育红 ZHANG Ling;SUN Yuan;GAO Chun-hua;SUI Hai-juan;YU Hai-ying;YANG Yu-hong(College of Basic Medical Sciences,Jinzhou Medical University,Jinzhou 121001,China;The First Hospital Affiliated to Jinzhou Medical University,Jinzhou 121001,China;College of Pharmacy,Jinzhou Medical University,Jinzhou 121001,China;Experimental Teaching Center for Basic Medical Sciences,Jinzhou Medical University,Jinzhou 121001,China)
机构地区:[1]锦州医科大学基础医学院,辽宁锦州121001 [2]锦州医科大学附属第一医院,辽宁锦州121001 [3]锦州医科大学药学院,辽宁锦州121001 [4]锦州医科大学基础医学实验教学中心,辽宁锦州121001
出 处:《中成药》2022年第11期3488-3492,共5页Chinese Traditional Patent Medicine
基 金:辽宁省科技厅自然科学基金指导计划项目(2019-ZD-0837);辽宁省药物作用与质量评价专业技术创新中心与辽宁省海洋生物活性物质重点实验室主任基金项目(2020-11)。
摘 要:目的研究红芪多糖对脂多糖(LPS)诱导小鼠脓毒症心肌病及相关信号通路的影响。方法50只小鼠随机分为空白组、LPS组及红芪多糖低、中、高剂量组(50、100、200 mg/kg)。红芪多糖组灌胃相应剂量红芪多糖,空白组和LPS组灌胃等量蒸馏水,连续给药14 d后,LPS组和红芪多糖组均一次性腹腔注射10 mg/kg LPS建立脓毒症心肌病小鼠模型,空白组则腹腔注射蒸馏水。造模后8 h,超声评估小鼠心功能,HE染色观察心肌组织变化,ELISA法检测炎性因子水平,RT-qPCR和Western blot法检测小鼠心肌组织TLR4、核因子κB(NF-κB)和NF-κB蛋白抑制蛋白α(IκBα)的mRNA和蛋白表达。结果与空白组比较,LPS组小鼠心功能降低(P<0.01),心肌组织发生病理改变,炎性因子释放增多(P<0.01),TLR4、NF-κB mRNA和蛋白表达,p-IκBα蛋白表达升高(P<0.01);红芪多糖可改善LPS诱导的小鼠各指标功能,且作用效果与药物剂量呈正相关。结论红芪多糖对LPS诱导小鼠脓毒症心肌病具有保护作用,其机制可能与调控TLR4/IκBα/NF-κB信号通路有关。AIM To investigate the effects of Hedysarum polybotrys polysacchcaides on the septic cardiomyopathy induced by lipopolysaccharide(LPS)and the related signaling pathways in mice.METHODS Fifty mice were randomly divided into blank group and LPS model group for 14-day gavage administration of distilled water,and trial groups for 14-day low dose(50 mg/kg),medium dose(100 mg/kg)and high dose(200 mg/kg)gavage of H.polybotrys polysacchcaides,respectively.Subsequently,LPS group and H.polybotrys polysacchcaide groups were injected intraperitoneally with 10 mg/kg LPS once to develop into septic cardiomyopathy mouse models,with the blank group dosed with distilled water through the identical administration route.Eight hours after modeling,the mice had their cardiac function evaluated by ultrasound;their myocardial tissue changes observed by HE staining;their inflammatory factors levels detected by ELISA;and their myocardiac mRNA and protein expressions of TLR4,nuclear factorκB(NF-κB)and NF-κB protein inhibitorα(IκBα)determined by RT-qPCR and Western blot.RESULTS Compared with the blank control group,LPS group displayed impaired cardiac function(P<0.01),increases in pathological changes in the myocardial tissue and inflammatory factors release(P<0.01),more expressions of TLR4 and NF-κB mRNA and protein and p-IκBαprotein(P<0.01).H.polybotrys polysacchcaides dose-dependently improved functions of LPS-induced mice in terms of each aforementioned index level.CONCLUSION H.polybotrys polysacchcaides protect LPS-induced septic cardiomyopathy in mice,and its mechanism may be related with their regulatory effect in TLR4/IκBα/NF-κB signaling pathway.
关 键 词:红芪多糖 脂多糖 脓毒症心肌病 TLR4/IκBα/NF-κB信号通路
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