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法舒地尔对急性心肌梗死大鼠心肌组织中ROCK2及TNF-α表达影响的研究

Effect of fasudil on the expressions of ROCK2 and TNF-αin the myocardial tissue of rats with acute myocardial infarction
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摘要 目的观察法舒地尔对急性心肌梗死大鼠心肌组织中ROCK2 mRNA和蛋白及TNF-α蛋白表达的影响,探讨法舒地尔对血性心肌梗死(AMI)大鼠的心肌保护作用。方法健康成年雄性SD大鼠48只,使用随机数字表法,将其分为对照组、假手术组(sham组)、心肌梗死模型组(AMI组)及心肌梗死后尾静脉注射盐酸法舒地尔组(AMI+HF组)。盐酸法舒地尔溶液浓度为30 mg/100 mL,给药剂量为4 mg/kg,该组大鼠自模型建立成功后立即首次给药,完成首次给药后开始计时,以后每6 h尾静脉注射HF 1次;AMI组及AMI+HF组大鼠开胸并结扎冠状动脉前降支建立心肌梗死模型。结扎成功6、24、48 h后无痛将其处死大鼠获取心肌组织;对照组大鼠不做处理,sham组大鼠开胸后,于大鼠冠状动脉穿线但不结扎冠状动脉(对照组及sham组大鼠每6 h尾静脉注射生理盐水1次),均无痛将其处死后获取心肌组织;使用Real-time PCR测定心肌组织中ROKC2 mRNA表达水平,使用蛋白质免疫印迹检测心肌组织中ROCK2及TNF-α蛋白表达水平。结果Sham组大鼠心肌组织中ROCK2 mRNA和蛋白及TNF-α蛋白表达与对照组比较差异均无统计学意义(P>0.05);在冠脉结扎6 h、24 h和48 h的时间点,AMI组大鼠、AMI+HF组大鼠心肌组织中ROCK2 mRNA和蛋白及TNF-α蛋白表达均高于sham组(P<0.05);在冠脉结扎6 h、24 h、48 h的时间点,AMI+HF组大鼠心肌组织中ROCK2 mRNA和蛋白及TNF-α蛋白表达均低于AMI组(P<0.05)。结论法舒地尔抑制AMI大鼠心肌组织中ROCK2表达,降低下游炎性因子TNF-α水平,这可能是法舒地尔具备保护心肌作用的机制之一。 Objective To observe the effects of fasudil on the expressions of ROCK2 and TNF-αin the myocardial tissue of rats with acute myocardial infarction(AMI),and to explore the myocardial protection of fasudil on AMI rats.Methods 48 healthy adult male SD rats were randomly divided into control group,sham operation group(sham group),myocardial infarction group(AMI group)and myocardial infarction after hydroxyfasudil injection through caudal vein group(AMI+HF group).The concentration of fasudil hydrochloride solution was 30mg/100mL,and the dosage was 4mg/kg.The rats in this group were immediately given fasudil hydrochloride for the first time after the establishment of the model.After that,fasudil hydrochloride was injected into the tail vein every 6 hours.Myocardial infarction models were established by thoracotomy and ligation of the anterior descending coronary artery in AMI and AMI+HF groups of rats.After successful ligation 6,24 and 48 hours,the rats were sacrificed to obtain myocardial tissue.The rats in the control group did not undergo any treatment,the sham operation group rats were given the thoracic coronary artery threading without coronary artery ligation.The technique of Real-time PCR was used to detect the expression of ROCK2 mRNA,and western blotting was used to detect the protein expression of Rock2 and TNF-α.Results Compared with the control group,the expression of Rock2 and Rock2 mRNA and TNF-αin myocardial tissue of sham group had no significant changes(P>0.05).At the time points of 6h,24h and 48h after coronary artery ligation,the expression of Rock2 and Rock2 mRNA in myocardial tissue of AMI group and AMI+HF group was significantly increased.The expressions of Rock2 and Rock2 mRNA and TNF-αprotein in AMI+HF group were significantly lower than those in AMI group(P<0.05).Conclusion Fasudil can inhibit the expression of Rock2 and reduce the level of TNF-αin myocardial tissue of AMI rats,which may be one of the mechanisms by which fasudil has a protective effect on the myocardium.
作者 张建银 邬容光 王强强 张淑红 马金秀 王艳 耑冰 陈乾 董辉 ZHANG Jianyin;WU Rongguang;WANG Qiangqiang;ZHANG Shuhong;MA Jinxiu;WANG Yan;ZHUAN Bing;CHEN Qian;DONG Hui(People’s Hospital of Ning Xia Hui Autonomous Region,Yinchuan 750002,China;The First Affiliated Hospital of Northwest University for Nationalities,Yinchuan 750002,China;Zhijiang People's Hospital of Hubei Province,Zhijiang 443200,China;General Hospital of Ningxia Medical University,Yinchuan 750004,China)
出处 《宁夏医学杂志》 CAS 2023年第8期679-683,共5页 Ningxia Medical Journal
基金 宁夏重点研发项目(2019BEG03045) 银川市科技创新项目(2021SF005)。
关键词 法舒地尔 急性心肌梗死 大鼠 ROCK2 Fasudil Acute myocardial infarction Rat ROCK2
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