The Mechanism Of Paclitaxel Intervention On Pulmonary Vascular Remodeling In Rats With Pulmonary Hypertension

Objective:Based on the observation of the Non-cytotoxic concentrations of paclitaxel on pulmonary vascular remodeling in rats with pulmonary hypertensiona and the mechanism of paclitaxel were explored.Methods:1.Establishment of model of pulmonary hypertension in rats: the model pulmonary hypertension rats was established with pneumonectomy plus MCT injection and morphology of lung tissue are observed:mPAP, and the ratio of RV to LV+S, percentage of small pulmonary arteries media thickness, degree of neointimal proliferation and muscularization of nonmuscular arteries in the region of the alveolar duct.2. To dectet the changes on pulmonary vascular remodeling in model group with paclitaxel treatment.3. To dectet the expressions of cell proliferation antigen Ki67in VSMCs by immunohistochemistry in each group.4. To dectet the expressions of cyclin-dependent kinase inhibitor P27Kip1and CyclinB1by immunohistochemistry and Western blot.Result:1.Pulmonary arterial hypertension in rats were established at the35d after left lung pneumonectomy plus MCT injection. The mPAP, the ratio of RV/(LV+S),pulmonary artery percentage of media thickness (WT%), the degree of non-muscle arterial muscle were (58.34±2.01) mm Hg,0.64±0.046,65.3±5.3%,80.7±8.6%, which were significantly higher than that in control group [(23.30±1.14) mmHg,0.32±0.028,16.2±1.3%,19.5±2.5%, P<0.01],compared with left lung pneumonectomy plus MCT injection rats respectively; the mPAP(42.35±1.53) mmHg,the ratio of RV/(LV+S)(0.44±0.029), WT%(30.5±2.6%), the degree of non-muscle arterial muscle (67.6±6.1%) in paclitaxel intervention group were significantly lower than the model group (P<0.01).2.Proliferation antigen Ki67expression in model group increased significantly,compared with control group(P<0.01);expression of proliferation antigen Ki67in paclitaxel intervention group decreased, compared with model group (P<0.01).But increased than the control group(P<0.01).3. Western blot test results and immunohistochemical method showed that expression of P27Kip1protein in model group decreased, compared with the control group(P<0.01);expression of P27Kip1protein in paclitaxel intervention group increased,compared with the model group(P<0.01).4.Expression of CyclinB1protein in model group increased,compared with the model group(P<0.01). Expression of CyclinB1protein in paclitaxel intervention group decreased, compared with the model group (P<0.01).Conclusion:1.The left lung resection and monocrotaline injection successfully induced obstructive pulmonary hypertension in rats.2.Non-cytotoxic concentrations of paclitaxel paclitaxel can reduce pulmonary hypertension in rats.3. Paclitaxel inhibition of pulmonary vascular smooth muscle cell proliferation may be related to the increased expression of P27Kip1and the decreased expression of CyclinB1.4.Non-cytotoxic concentrations of paclitaxel may prevent the development of pulmonary hypertension.