阿托伐他汀对肺动脉高压大鼠右心室重构的影响

发布时间：2018-08-06 11:18

【摘要】：目的：本实验主要是观察阿托伐他汀对野百合碱（MCT）诱导肺动脉高压大鼠的肺动脉压力及右心室重构的影响，探讨缝隙连接蛋白43（Cx43）与心肌肌钙蛋白T(cTn-T)在肺动脉高压所致右心室重构中的作用，以及阿托伐他汀对其影响。 方法：将雄性SD大鼠40只，随机分为5组，每组8只，即空白对照组（Ctr组）、肺动脉高压组（MCT组）、阿托伐他汀10mg干预组（Ato1组）、阿托伐他汀20mg干预组（Ato2组）、地尔硫卓干预组（Dil组），分别予MCT组、Ato1组、Ato2组、Dil组大鼠一次性颈背部皮下注射2%MCT（以50mg/kg），Ctr组予1ml生理盐水皮下注射。自注射MCT次日起，分别将阿托伐他汀予Ato1组10mg/kg.d、Ato2组20mg/kg.d灌胃,Dil组予地尔硫卓25mg/kg.d灌胃，Ctr组、MCT组予等量蒸馏水灌胃。3周后达实验终点，采用右心导管法测定各组大鼠肺动脉平均压（mPAP）、右心室收缩压（RVSP）；用ELISA法测血浆cTnT浓度；计算右心室肥厚指数（RVHI），即右心室与左室加室间隔的重量比值[RV/(LV+IVS)]；右心室心肌组织采用HE染色，光镜下观察右心室心肌的形态学改变；采用免疫组织化学法观察右心室心肌Cx43表达的变化。 结果：MCT组大鼠肺动脉平均压（mPAP）、右心室收缩压（RVSP）、右心室肥厚指数（RVHI）、cTnT显著高于Ctr组（P0.001），各干预组（Ato1组、Ato2组、Dil组）上述指标均低于MCT组（P0.001），但仍高于Ctr组（P0.001）；各干预组之间肺动脉平均压、右心室收缩压无明显差别（P0.05）；Ato2组的右心室肥厚指数低于Ato1组（P0.001），但与Dil组无明显差别（P0.05）；Ato2组的cTnT低于Ato1组（P0.01），但也与Dil组无明显差别（P0.05）；与Ctr组相比，MCT组大鼠右心室心肌细胞肥大、肌纤维紊乱伴有炎性细胞浸润和结缔组织增生，而各干预组的右心室心肌形态改变在两者之间；同Ctr组相比，MCT组大鼠右心室心肌Cx43分布位置发生改变，染色强度减弱，表达减少（P0.001），，而各干预组的Cx43表达情况介于Ctr组和MCT组之间(P0.05)。 结论:阿托伐他汀能降低野百合碱诱导大鼠的肺动脉压力，改善心肌重构，降低血浆cTnT的浓度和增加右心室心肌Cx43表达。阿托伐他汀对右心室肥厚程度和cTnT的影响呈剂量依赖性；阿托伐他汀逆转右心室重构机制可能与改善右心室心肌Cx43的分布有关。
[Abstract]:Objective: to observe the effects of Atto vastatin on pulmonary artery pressure and right ventricular remodeling in monocrotaline (MCT) induced pulmonary hypertension rats. To investigate the role of gap junction protein 43 (Cx43) and cardiac troponin T (cTn-T) in right ventricular remodeling induced by pulmonary hypertension and the effect of Atto vastatin. Methods: forty male SD rats were randomly divided into 5 groups with 8 rats in each group. Namely blank control group (Ctr group), pulmonary hypertension group (MCT group), Atto vastatin 10mg intervention group (Ato1 group), Atto vastatin 20mg intervention group (Ato2 group), diltiazem intervention group (Dil group), MCT group, Ato1 group, Ato2 group rats' cervical dorsum, respectively. 2%MCT (50mg/kg) group was subcutaneously injected with 1ml saline. Since the day after MCT was injected, Atto vastatin was given to Ato1 group (10 mg / kg 路d ~ (2) 20mg/kg.d intragastric perfusion respectively, and Dil group was given diltiazem 25mg/kg.d intragastric perfusion and CTR group was given the same amount of distilled water for 3 weeks to reach the end point of the experiment. The mean pulmonary artery pressure (mPAP),) and the right ventricular systolic pressure (RVSP);) were measured by right ventricular catheterization in rats. The plasma cTnT concentration was measured by ELISA method, and the right ventricular hypertrophy index (RVHI),) was calculated as the weight ratio of right ventricle to left ventricular septum [RV/ (LV IVS)]. The morphologic changes of right ventricular myocardium were observed by HE staining under light microscope and the expression of Cx43 in right ventricular myocardium was observed by immunohistochemical method. Results the mean pulmonary artery pressure (mPAP),) of the rats in the (mPAP), group was significantly higher than that in the Ctr group (P0.001). The above indexes in each intervention group (Ato1 group, Ato2 group, Dil group) were lower than those in the MCT group (P0.001), but still higher than that in the Ctr group (P0.001). There was no significant difference in the mean pulmonary artery pressure and right ventricular systolic pressure between the intervention groups (P0.05). The right ventricular hypertrophy index in the Ato2 group was lower than that in the Ato1 group (P0.001), but there was no significant difference between the Ato2 group and the Dil group (P0.05). The cTnT of the Ato2 group was lower than that of the Ato1 group (P0.01), but there was no significant difference with the Dil group (P0.05). Compared with Ctr group, right ventricular cardiomyocyte hypertrophy, muscle fiber disturbance accompanied by inflammatory cell infiltration and connective tissue proliferation were observed in MCT group, and the morphologic changes of right ventricular myocardium in each intervention group were in between. Compared with Ctr group, the distribution of Cx43 in right ventricular myocardium of rats in MCT group was changed, the staining intensity was decreased and the expression of Cx43 was decreased (P0.001), while the expression of Cx43 in each intervention group was between Ctr group and MCT group (P0.05). Conclusion: Atto vastatin can reduce pulmonary artery pressure, improve myocardial remodeling, decrease plasma cTnT concentration and increase Cx43 expression in right ventricular myocardium of rats induced by monocrotaline. The effect of Atto vastatin on the degree of right ventricular hypertrophy and cTnT was dose-dependent, and the mechanism of Atto vastatin reversing right ventricular remodeling might be related to improving the distribution of Cx43 in right ventricular myocardium.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965

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