| Objective:In this study, we established animal model ofpulmonary arterial hypertension in rats by left pneumonectomy plusMCT injection, and understood the characteristics of pulmonary vascularand ventricular remodeling and the level of expression and activity ofRho kinase in this model. Methods:1. Male SD rats(300-350g) wererandomly divided into five groups(12rats in each group). Group C: notaccept any treatment; Group J: slit and exposure the left chest, theexposure same as pneumonectomy; Group M: left pneumonectomy plusMCT (60mg/kg) injection at subcutaneous; Group F1: leftpneumonectomy plus MCT injection and fasudil (2mg/Kg.d) treatmentthrough the tail vein21days after surgery; Group F2: leftpneumonectomy plus MCT injection and fasudil treatment through thetail vein7days after surgery. All rats were feeded under the samecondition.2.35days after operation, we determinate mean pulmonaryartery pressure by right heart catheterization after the rats were chloralhydrate anesthesia.3. We remove the heart and lungs after the rats wereexecuted; calculate the ratio of RV/LV+S to understand the situation ofventricular remodeling.4. HE staining, Immunohistochemical staining and Elastin-Van Gieson staining were used to observe the morphologicalchanges of pulmonary artery and pulmonary tissue, and detect some ofthe results those can represent the characteristics of pulmonary arterialremodeling, such as degree of neointimal proliferation, VOS, percentwall thickness (WT%), percent wall area(WA%) and percent lumen area(LA%).5. The expression of ROCK1and ROCK2mRNA to beeninvestigated by RT-PCR.6. Measuring the expression of p-MYPT whatrepresent the Rho kinase activity. Result:1. During the experiment, allrats have some performance, such as weight gain or even decline, loosehair, reduced activity, shortness of breath and so on. There were five deadrats in group M and one in group F1, the rest were alive and the appealslight.2. Compared with the group C and group J, The mPAP of group Mincreased significantly [(58.56±3.56vs.22.36±1.75and23.31±1.51)mmHg]（P﹤0.001）; Give fasudil intervention, compared with group M,the mPAP of group F1and group F2significantly decreased[(39.99±4.10and34.76±7.36vs.58.56±3.56) mmHg](P＜0.01), and thegroupF2decreased more obviously(P＜0.05).3. Compared with the groupC and group J, the ratio of RV/LV+S in group M increasedsignificantly(0.61±0.08vs.0.29±0.04and0.31±0.04), P＜0.001);Give fasudil intervention, the ratio of RV/LV+S in group F1and groupF2significantly decreased (0.46±0.07and0.36±0.08vs.0.61±0.08,P﹤0.01), and the group F2decreased more obviously (P＜0.05).4. Detection of lung tissue stereological targets, compared with the group Cand group J, the WT%, WA%, muscularization, degree of neointimalproliferation, VOS of group M was significantly higher (P<0.001), andthe LA%decrease more; After fasudil intervention, the stereologicalindicators of group F1and group F2significantly reduced （P<0.001）,and group F2were more obvious（P＜0.001）.4. Compared with thegroup C and group J, the expression of ROCK1and ROCK2mRNA ofgroup M increased significantly（P＜0.001）; After Fasudil intervention,the expression of ROCK1and ROCK2mRNA of group F1and group F2significantly decreased (P＜0.01), and the groupF2decreased more.6.Compared with the group C and group J, the expression level of p-MYTPin lung tissue of group M increased significantly (P＜0.0001）; AfterFasudil intervention, the expression level of p-MYTP in lung tissue ofgroup F1and group F2significantly decreased (P＜0.0001）, and thegroupF2decreased more (P＜0.001). Conclusions:1. The left lungresection and MCT injection can effectively establish pulmonaryhypertension rat models, this model has the typical manifestations ofpulmonary ascular remodeling and neointima formation.2. Fasudil caninhibit pulmonary vascular remodeling of rat model of pulmonary arterialhypertension induced by left lung resection plus inject MCT. |
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