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机构地区:[1]山东省医学科学院药物研究所,济南250062 [2]济南大学,山东省医学科学院医学与生命科学学院,济南250062
出 处:《医药导报》2016年第10期1041-1045,共5页Herald of Medicine
基 金:国家科技重大专项子课题(2009ZX09301-013);山东省自然科学基金资助项目(ZR2009CM089)
摘 要:目的探讨诺迪康胶囊对运动性心肌损伤的保护机制。方法通过大鼠负荷游泳建立力竭性心肌损伤模型,健康Wistar雄性大鼠70只,随机分为3组:正常对照组、模型对照组、诺迪康胶囊组。正常对照组(n=10),不进行任何运动;模型对照组(n=30),大鼠尾束相当于体质量2%负荷,进行力竭游泳运动时间不少于3 h;诺迪康胶囊组(n=30):造模方法同模型对照组,运动前灌胃给予诺迪康胶囊0.45 g·kg-1(有效剂量),每日1次,连续10 d。模型对照组和诺迪康胶囊组大鼠分别于力竭运动后3,6,24 h腹腔注射20%乌拉坦0.2 m L·(100 g)-1。苏木精-伊红(HE)染色观察大鼠心肌病理学变化,分别于力竭运动后3,6和24 h取心肌组织进行匀浆,取上清液,Western blotting法测定磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)、核转录因子κB(NF-κB)、肿瘤坏死因子-α(TNF-α)蛋白表达的变化。结果病理学检查结果显示,模型对照组大鼠心肌细胞排列紊乱,横纹消失,与模型对照组比较,诺迪康胶囊各组大鼠心肌损伤减轻。与正常对照组比较,模型对照组大鼠运动后不同时间心肌组织中p-p38MAPK、NF-κB、TNF-α蛋白表达均显著上调(P<0.01),而诺迪康胶囊可明显抑制其表达的上调(P<0.01)。结论诺迪康胶囊对大鼠力竭性运动诱发心肌损伤具有保护作用,其作用机制可能与下调p-p38MAPK、NF-κB和TNF-α的表达,抑制过度炎症反应有关。Objective To observe the effect of Nuodikang capsule preconditioning on the expression change of p38MAPK,NF-κB,TNF-α at different time points in myocardial injury induced by acute exhausted exercises,and to explore the protective effects of Nuodikang capsule and the underlying mechanism. Methods The myocardial injury animal model was set up by using an exhaustion swimming exercise.Male Wistar rats (n=70) were randomly divided into 3 groups: the normal control group (n=10),without exercise; the model control group (n=30),the rats were loaded with 2% body mass on the tails and swam for more than 3 h;the Nuodikang capsule group (n=30),the rats were modeled just like the model control group,and before modeling,0.45 g·kg-1Nuodikang capsule was given once daily,for consecutive 10 days.HE staining was used to observe the myocardial pathology change in the rats.The myocardial tissues were removed at 3,6 and 24 h after modeling.The protein expression levels of p38MAPK,NF-κB,TNF-α were detected by Western blotting. Results According to the results of pathology examination,the myocardial cells arranged disorder and the horizontal stripes disappeared in the model control group.Compared with the model control group,the myocardial injury was alleviated in the Nuodikang capsule group.Compared with the normal control group,the protein expression levels of p38MAPK,NF-κB and TNF-α were significantly increased in the model control group(P〈0.01) and there was a certain inhibition in the Nuodikang capsule group(P〈0.01). Conclusion These findings indicated that the Nuodikang capsule has protective effect on the myocardial indury induced by exhausted exercises,and its mechanism may be that it can reduce the expression of p38MAPK,NF-κB and TNF-α and restrain the exaggerated inflammation reaction.
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