利舒康胶囊通过Nrf2/HO-1途径减轻模拟高原缺氧大鼠心肌组织损伤  

Lishukang Capsule Attenuates Myocardial Injury in Rats with High Altitude Hypoxia by Nrf2/HO-1 Pathway

作　　者：田贻婷 孟盼盼 蔡楠 谭宏强 张朋朋 马慧萍[1,2] TIAN Yiting;MENG Panpan;CAI Nan;TAN Hongqiang;ZHANG Pengpeng;MA Huiping(Department of Pharmacy,the 940th Hospital of Joint Logistics Support Force of PLA,the Lab of PLA for High Altitude Medicine,Lanzhou 730050,China;College of Pharmacy,Gansu University of Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]中国人民解放军联勤保障部队第940医院药剂科全军高原医学实验室,兰州730050 [2]甘肃中医药大学药学院,兰州730000

出　　处：《实验动物科学》2023年第5期71-75,共5页Laboratory Animal Science

基　　金：国家自然科学基金(81571847);军队卫勤保障能力创新与生成专项计划项目(21WQ045);甘肃省自然科学基金项目(22JR11RA011)。

摘　　要：目的研究利舒康胶囊对模拟高原缺氧损伤大鼠心肌组织的保护作用及其机制。方法建立高原缺氧大鼠损伤模型,将60只Wistar雄性大鼠随机分为正常对照组、缺氧模型组、阳性药红景天胶囊组(420 mg/kg),以及不同浓度利舒康胶囊组(280、420、560 mg/kg),每组10只。正常对照组和缺氧模型组给予等体积的灭菌注射用水,连续给药7 d。第7天给药50 min后除正常对照组外,其余各组均放入大型低压低氧动物实验舱模拟高原海拔8000 m缺氧12 h,12 h后将海拔降至3500 m安乐死大鼠,取心肌组织进行超微病理结构观察,Western blot法检测各组大鼠心肌组织胞质中Nrf2、HO-1的表达变化及胞核中Nrf2表达。结果透射电镜结果显示,与正常对照组相比,缺氧模型组大鼠心肌细胞线粒体外膜破坏,明显肿胀,心肌损伤严重,组织Nrf2、HO-1表达增加(P<0.05或P<0.01);与缺氧模型组相比,红景天胶囊组和利舒康高剂量组心肌损伤明显改善,心肌细胞肌丝完整,线粒体结构完整,组织Nrf2、HO-1表达降低(P<0.05),利舒康低、中、高剂量组均有降低趋势,且利舒康高剂量组与缺氧模型组相比具有显著性差异(P<0.05)。结论利舒康胶囊对高原缺氧所致心肌损伤具有保护作用,其机制可能与激活Nrf2/HO-1信号通路有关。Objective To study the protective effect and mechanism of Lishukang capsule on myocardial tissue induced by hypoxia at simulated altitude in rats.Method Sixty male Wistar rats were randomly divided into normal control group,hypoxia model group,positive rhodiola capsule group(420 mg/kg),and different concentrations of Lishukang capsule groups(280,420,560 mg/kg),with 10 rats in each group.Normal control group and hypoxia model group were given equal volume of water for injection for 7 consecutive days.50 min after the 7th day of administration,except for the normal control group,all groups were put into large low-pressure and hypoxic animal laboratory chamber to simulate the altitude of 8000 m and hypoxia for 12 h.After 12 h,the rats were sacrificed by lowering the altitude to 3500 m,and the myocardial tissue was taken for ultrastructural observation.The expression changes of Nrf2 and HO-1 in cytoplasm and Nrf2 in nucleus were detected by Western blot.Result Compared with the normal control group,the mitochondrial outer membrane of myocardial cells in hypoxia model group was destroyed,obviously swelling,serious myocardial injury,and the expression of Nrf2 and HO-1 in tissues increased(P<0.05 or P<0.01);Compared with the hypoxia model group,the myocardial injury in the rhodiola capsule group and rishokang high-dose group was significantly improved,with intact myofilm and mitochondrial structure,and the expression of Nrf2 and HO-1 decreased(P<0.05),there was a decreasing trend in risocan low-dose,medium-dose and high-dose groups,and there was a significant difference in risocan high-dose groups(P<0.05).Conclusion Lishukang capsule has protective effect on myocardial injury caused by altitude hypoxia,and its mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.

关 键 词：缺氧损伤 利舒康胶囊 心肌组织 Nrf2/HO-1通路 

分 类 号：Q95-3[生物学—动物学]