【摘要】 目的通过建立3种大鼠肺动脉高压(PAH)模型,研究生存素(Survivin)及半胱氨酸蛋白酶-3(Caspase-3)在肺动脉高压中肺组织的作用及其相关性。方法采用单纯A-VF、MCT、MCT+A-VF 3种方法建立大鼠PAH模型;检测模型大鼠平均肺动脉压力(m PAP)、右心肥厚指数RV/(LV+S)比值,观察三组肺动脉高压严重程度;采用免疫组化检测Survivin及Caspase-3在三组动物模型肺组织中的表达水平。结果三组PAH模型m PAP及RV/(LV+S)较对照组均有不同程度的升高(P<0.05),MCT+A-VF组较MCT组及A-VF组升高更明显(P<0.05),而MCT组比A-VF组高(P<0.05),其中MCT组及MCT+A-VF组形成肺动脉高压。三组PAH模型组都在动脉内、外膜及周围出现Survivin阳性表达细胞,而在对照组中未出现;在MCT+A-VF组中阳性细胞的数量及着色强度均较MCT组和A-VF组高(P<0.05),MCT组比A-VF组高(P<0.05)。Caspase-3在四组动脉内、中、外膜及周围中均为阳性表现,对照组均比模型组阳性强度高(P<0.05),A-VF组较MCT组及MCT+A-VF组高(P<0.05),MCT组较MCT+A-VF组高(P<0.05),MCT+A-VF组最低。两个因子之间呈负相关。结论Survivin及Caspase-3都参与了肺动脉高压的形成,Survivin可能是通过抑制Caspase-3的活化而抑制细胞凋亡,Survivin及Caspase-3有望成为治疗肺动脉高压的两个新靶点。更多还原

【Abstract】 Objective To establish three kinds of rats model of pulmonary artery hypertension(PAH) and explore the role and their correlation of Survivin, Caspase-3 in pulmonary artery hypertension of rats. Methods PAH models of rats were established by three methods: A-VF, MCT and MCT + A-VF. The mean pulmonary artery pressure(m PAP), and the ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV + S)] were detected. The expressions of Survivin and Caspase-3 in three kinds of PAH models were detected by immunohistochemistry. Results The values of m PAP and RV/(LV + S) of three kinds of PAH models were higher than those of control group(P <0.05), the MCT + A-VF group increased more significantly than the MCT group and A-VF group(P <0.05), and the MCT group increased more significantly than the A-VF group(P <0.05). The Survivin expressed in the inner and outer membrane of arteries and the surrounding in the three kinds of PAH model groups, but it did not appear in the control group. The number of positive cells and tinting strength in the MCT + A-VF group were more than that in the MCT group and A-VF group(P <0.05), and the MCT group was higher than A-VF group(P <0.05). The Caspase-3 expressed in the inner, middle and outer membrane of arteries and the surrounding in all groups, the control group was higher than the model groups in the positive intensity(P <0.05), the A-VF group was higher than the MCT group and MCT + A-VF group(P <0.05), and the MCT group was higher than the MCT + A-VF group(P <0.05). There was a negative correlation between Survivin and Caspase-3. Conclusions Both Survivin and Caspase-3 are involved in the formation of PAH. Survivin may inhibits apoptosis by inhibiting the activation of Caspase-3. Survivin and Caspase-3 are expected to be new therapy targetings for PAH.更多还原