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卡巴胆碱对心肌肥厚大鼠模型的心肌保护作用及机制探讨
Myocardial protective effect of carbachol on rat model of myocardial hypertrophy and its mechanism
【摘要】 目的研究卡巴胆碱对心肌肥厚大鼠模型的心肌保护作用及具体机制。方法根据大鼠体重随机分为对照组、模型组和实验组,每组15只。用异丙肾上腺素(ISO)诱导大鼠心肌肥厚模型,建模完成后实验组腹腔注射30 mg·kg-1卡巴胆碱,每天2次,持续2周;模型组和对照组则给予等量0. 9%NaCl腹腔注射。以超声心动图检测各组大鼠左心室后壁及室间隔在收缩期与舒张期的厚度;以苏木精-伊红(HE)染色观察大鼠心肌组织病理学形态;以蛋白质印迹法检测核因子-κB(NF-κB)信号通路表达水平。结果对照组、模型组和实验组大鼠收缩期室间隔厚度(IVSs)分别为(2. 56±0. 36),(3. 98±0. 27),(3. 05±0. 34) mm,舒张期左心室后壁厚度(LVPWd)分别为(1. 75±0. 18),(2. 84±0. 32),(2. 03±0. 14) mm;心脏重量与体重比值(HW/BW)分别为(2. 86±0. 23),(5. 36±0. 69),(3. 36±0. 28) mg·g-1,左心室重量与体重比值(LV/BW)分别为(0. 69±0. 03),(1. 46±0. 13),(0. 86±0. 05) mg·g-1;心肌横切面直径分别为(10. 23±2. 36),(35. 26±3. 47),(18. 63±2. 47) mm;心肌组织中NF-κB p65蛋白相对表达量分别为0. 66±0. 25,1. 59±0. 13,1. 24±0. 09,IκBα蛋白相对表达量分别为1. 36±0. 21,0. 56±0. 08,1. 24±0. 16,差异均有统计学意义(均P <0. 05)。结论卡巴胆碱可通过抑制NF-κB信号通路活化来逆转由ISO诱导的大鼠心肌肥厚,从而保护心肌。
【Abstract】 Objective To investigate the protective effect of carbachol on myocardium and its specific mechanism in rats with myocardial hypertrophy. Methods According to the weight,rats were randomly divided into control group,model group and test group,15 rats in each group.Isoproterenol( ISO) was used to induce myocardial hypertrophy in rats.After the establishment of model,test group was intraperitoneally injected with 30 mg·kg-1 carbachol twice a day for 2 weeks,while model group and control group were intraperitoneally injected with 0. 9% NaCl. The thickness of left ventricular posterior wall and interventricular septum in systolic and diastolic phase was measured by echocardiography; the histopathological morphology of myocardium was observed by hematoxylin-eosin( HE) staining; and the expression level of nuclear factor-κB( NF-κB) signal pathway was detected by Western blot. Results Interventricular septum thickness in systole( IVSs) in control group,model group and test group were( 2. 56 ± 0. 36),( 3. 98 ± 0. 27),( 3. 05 ± 0. 34) mm; left ventricular posterior wall thickness in diastole( LVPWd) were( 1. 75 ± 0. 18),( 2. 84 ± 0. 32),( 2. 03 ± 0. 14) mm; heart weight to body weight ratio( HW/BW) were( 2. 86 ± 0. 23),( 5. 36 ± 0. 69),( 3. 36 ± 0. 28) mg·g-1,left ventricular weight to body weight ratio( LV/BW) were( 0. 69 ± 0. 03),( 1. 46 ± 0. 13),( 0. 86 ± 0. 05) mg·g-1; the diameters of myocardial transverse plane were( 10. 23 ± 2. 36),( 35. 26 ± 3. 47),( 18. 63 ± 2. 47) mm; the relative expression levels of NF-κB p65 protein in myocardial tissue were 0. 66 ± 0. 25,1. 59 ± 0. 13,1. 24 ± 0. 09,the relative expression levels of IκBαprotein were 1. 36 ± 0. 21,0. 56 ± 0. 08,1. 24 ± 0. 16; all with significant difference( all P < 0. 05). Conclusion Carbachol can reverse myocardial hypertrophy induced by ISO by inhibiting the activation of NF-κB signaling pathway,thus protecting myocardium.
【Key words】 carbachol; nuclear factor-κB signaling pathway; myocardial hypertrophy; isoproterenol;
- 【文献出处】 中国临床药理学杂志 ,The Chinese Journal of Clinical Pharmacology , 编辑部邮箱 ,2019年18期
- 【分类号】R965;R-332
- 【下载频次】159