【摘要】：目的：本實驗主要是觀察阿托伐他汀對野百合堿（MCT）誘導肺動脈高壓大鼠的肺動脈壓力及右心室重構(gòu)的影響，探討縫隙連接蛋白43（Cx43）與心肌肌鈣蛋白T(cTn-T)在肺動脈高壓所致右心室重構(gòu)中的作用，以及阿托伐他汀對其影響。 方法：將雄性SD大鼠40只，隨機分為5組，每組8只，即空白對照組（Ctr組）、肺動脈高壓組（MCT組）、阿托伐他汀10mg干預組（Ato1組）、阿托伐他汀20mg干預組（Ato2組）、地爾硫卓干預組（Dil組），分別予MCT組、Ato1組、Ato2組、Dil組大鼠一次性頸背部皮下注射2%MCT（以50mg/kg），Ctr組予1ml生理鹽水皮下注射。自注射MCT次日起，分別將阿托伐他汀予Ato1組10mg/kg.d、Ato2組20mg/kg.d灌胃,Dil組予地爾硫卓25mg/kg.d灌胃，Ctr組、MCT組予等量蒸餾水灌胃。3周后達實驗終點，采用右心導管法測定各組大鼠肺動脈平均壓（mPAP）、右心室收縮壓（RVSP）；用ELISA法測血漿cTnT濃度；計算右心室肥厚指數(shù)（RVHI），即右心室與左室加室間隔的重量比值[RV/(LV+IVS)]；右心室心肌組織采用HE染色，光鏡下觀察右心室心肌的形態(tài)學改變；采用免疫組織化學法觀察右心室心肌Cx43表達的變化。 結(jié)果：MCT組大鼠肺動脈平均壓（mPAP）、右心室收縮壓（RVSP）、右心室肥厚指數(shù)（RVHI）、cTnT顯著高于Ctr組（P0.001），各干預組（Ato1組、Ato2組、Dil組）上述指標均低于MCT組（P0.001），但仍高于Ctr組（P0.001）；各干預組之間肺動脈平均壓、右心室收縮壓無明顯差別（P0.05）；Ato2組的右心室肥厚指數(shù)低于Ato1組（P0.001），但與Dil組無明顯差別（P0.05）；Ato2組的cTnT低于Ato1組（P0.01），但也與Dil組無明顯差別（P0.05）；與Ctr組相比，MCT組大鼠右心室心肌細胞肥大、肌纖維紊亂伴有炎性細胞浸潤和結(jié)締組織增生，而各干預組的右心室心肌形態(tài)改變在兩者之間；同Ctr組相比，MCT組大鼠右心室心肌Cx43分布位置發(fā)生改變，染色強度減弱，表達減少（P0.001），，而各干預組的Cx43表達情況介于Ctr組和MCT組之間(P0.05)。 結(jié)論:阿托伐他汀能降低野百合堿誘導大鼠的肺動脈壓力，改善心肌重構(gòu)，降低血漿cTnT的濃度和增加右心室心肌Cx43表達。阿托伐他汀對右心室肥厚程度和cTnT的影響呈劑量依賴性；阿托伐他汀逆轉(zhuǎn)右心室重構(gòu)機制可能與改善右心室心肌Cx43的分布有關(guān)。
[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.
【學位授予單位】：皖南醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R965

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