芪苈强心胶囊对慢性心力衰竭大鼠心功能及肾脏AQP2表达的影响及其机制研究

【作者】 张健；

【导师】 崔向宁；

【作者基本信息】 北京中医药大学 ， 中西医结合临床， 2014， 硕士

【摘要】 1目的观察芪苈强心胶囊对心梗后心力衰竭大鼠心功能及血浆AVP、AngⅡ变化和AQP2、pS256-AQP2、V2R、AT1R蛋白表达的影响,探讨苠苈强心胶囊对慢性心力衰竭大鼠心脏功能及水代谢紊乱的影响及其可能的分子机制。2方法2.1选取50只雄性健康SD大鼠(假手术组10只和造模组40只)。造模组采用左冠状动脉前降支结扎的方法制备慢性心衰模型,造模4周后超声心动图检测,取LVEF≤45%者再随机分为3组：模型组,芪苈强心组,缬沙坦组。给药4周后再行超声心动图检测各指标的变化。2.2采用放射性免疫法检测血浆AVP, AngⅡ的变化。2.3采用免疫组织化学方法和western blotting的方法检测AQP2、 pS256-AQP2、 V2R及AT1R的表达。3结果3.1与假手术相比,模型组EF, FS, SV明显降低(P<0.05),LVIDd,LVIDs,EDV,ESV(P<0.05)则显著升高。和模型组相比,芪苈强心组和缬沙坦组EF, FS显著升高(P<0.05),LVIDs, ESV显著降低(P<0.05),芪苈强心组和缬沙坦组LVIDd, EDV与模型组相比,虽有减少趋势,但差异无统计学意义(P>0.05),芪苈强心组和缬沙坦组SV与模型组相比,差异无统计学意义(P>0.05)。芪苈强心组与缬沙坦组EF,FS, LVIDs, ESV差异亦无统计学意义(P>0.05)。3.2放射性免疫法检测结果显示：与假手术组相比,模型组血浆AVP、AngⅡ明显升高(P<0.05)；与模型组相比,芪苈强心组和缬沙坦组血浆AVP、AngⅡ明显降低(P<0.05)；同时芪苈强心组与缬沙坦组血浆AVP、AngⅡ水平相当,差异无统计学意义(P>0.05)。3.3模型组AQP2、pS256-AQP2、V2R、AT1R蛋白表达水平明显升高(P<0.05)；与模型组相比,芪苈强心和缬沙坦组AQP2、pS256-AQP2、V2R、AT1R表达均明显降低(P<0.05),同时芪苈强心组与缬沙坦组AQP2、pS256-AQP2、V2R、AT1R表达比较,差异无统计学意义(P>0.05)。4结论4.1芪苈强心胶囊对大鼠心肌梗死后心力衰竭的心功能及水潴留有改善作用,与ARB类药物缬沙坦胶囊作用相当。4.2芪苈强心胶囊减轻水潴留的作用与抑制AQP2及pS256-AQP2的表达及重新分布,减少肾集合管水重吸收有关。4.3芪苈强心胶囊对肾脏AQP-2的调节可能是通过AVP-V2R-AQP2和AngⅡ-AT1R-AQP2途径。更多还原

【Abstract】 1ObjectiveTo observe the effect Qiliqiangxin capsule on rats with heart failure after myocardial infarction heart function and plasma AVP, Ang II changes and AQP2, pS256-AQP2, V2R, AT1R protein expression.Discussion Qiliqiangxin capsule on chronic heart failure function and water metabolism in rats and its possible molecular mechanisms.2Method2.1Select50healthy male SD rats (sham group10and made module40). Modules made using the left anterior descending coronary artery ligation model of chronic heart failure were prepared, after4weeks, echocardiography,take LVEF≤45%were randomly divided into three groups:model group, Qiliqiangxin group valsartan group.Administered four weeks after the line changes echocardiography each index.2.2Using radioimmunoassay plasma AVP, Ang II of change.2.3Using immunohistochemistry and western blotting method to detect AQP2, pS256-AQP2, V2R and AT1R expression.3Result3.1And sham compared with the model group EF, FS, SV was significantly lower (P<0.05), LVIDd, LVIDs, EDV, ESV (P<0.05), significantly increased. And the model group compared Qiliqiangxin group and valsartan group EF, FS was significantly higher (P<0.05), LVIDs, ESV was significantly lower (P<0.05), Qiliqiangxin group and valsartan group LVIDd, EDV compared with the model group, although a decreasing trend, but the difference was not statistically significant (P>0.05), Qiliqiangxin SV group and valsartan group compared with the model group, the difference was not statistically significant (P>0.05). Qiliqiangxin group and valsartan group EF, FS, LVIDs, ESV difference was not statistically significant (P>0.05).3.2Show radioimmunoassay test results:Compared with the sham group, model group, the plasma AVP, Ang II was significantly higher (P<0.05); compared with the model group, Qiliqiangxin group and valsartan plasma AVP, Ang II significantly lower (P<0.05); while Qiliqiangxin group and valsartan plasma AVP, Ang II levels considerably, the difference was not statistically significant (P>0.05).3.3Modelgroup AQP2, pS256-AQP2, V2R, AT1R protein expression levels were significantly increased (P<0.05); compared with the model group, AQP2, pS256-AQP2, V2R, AT1R expression Qiliqiangxin and valsartan group were significantly lower (P<0.05), two AQP2, pS256-AQP2, V2R, AT1R expression, the difference was not statistically significance (P>0.05)4Conclusion 4.1Qiliqiangxin capsule on heart failure after myocardial infarction in rats and water retention left ventricular function improvement, and ARB drugs valsartan capsules considerable role.4.2Qiliqiangxin capsules to reduce water retention and the role of inhibiting the expression and redistribution of AQP2and pS256-AQP2reduce the renal collecting duct water reabsorption related.4.3Qiliqiangxin capsule of the kidney AQP2regulation may be through AVP-V2R-AQP2and Ang Ⅱ-AT1R-AQP2way.更多还原