摘要目的 探讨T型钙通道阻滞剂ProTx-1、micromolar Ni2+及米贝地尔对野百合碱(MCT)诱导大鼠肺动脉高压形成的影响.方法 雄性SD大鼠40只,按随机数字表法随机分为5组:正常对照组、MCT组、ProTx-1干预组、micromolar Ni2+干预组及米贝地尔干预组,每组8只.实验第28天检测各组大鼠右心室收缩压(RVSP)、右心肥厚指数(RVHI)和肺血管壁占血管总面积百分比(MA％).采用蛋白印迹法检测增殖细胞核抗原(PCNA)和激活型半胱氨酸天冬氨酸蛋白酶3(Cleaved Caspase-3)在肺动脉平滑肌中表达情况.结果 1.MCT组大鼠RVSP、RVHI均高于其他各组,差异均有统计学意义(F=21.55,P＜0.01;F=15.63,P＜0.01);各干预组RVSP、RVHI虽高于正常对照组,但较MCT组明显降低,差异均有统计学意义(均P＜0.05),各干预组间差异无统计学意义.2.MCT组大鼠MA％[(80.24±4.30)％]显著高于正常对照组[(23.43±1.95)％],差异有统计学意义(P＜0.01),ProTx-1干预组[(60.35±3.83)％]、micromolar Ni2+干预组[(62.“±3.81)％]和米贝地尔干预组[(58.66±4.23)％]的MA％虽高于正常对照组,但明显低于MCT组(F=216.2,P＜0.01);各干预组MA％比较差异无统计学意义(均P＞0.05).3.相较于正常对照组,MCT组大鼠肺动脉平滑肌内PCNA蛋白表达明显上调,各干预组PCNA蛋白表达水平均明显低于MCT组.MCT组大鼠Cleaved Caspase-3蛋白表达高于正常对照组,而3个干预组与MCT组比较差异无统计学意义.结论 T型钙通道阻滞剂ProTx-1、micromolar Ni2及米贝地尔能有效干预MCT诱导大鼠肺动脉高压形成,并抑制其肺动脉平滑肌细胞的增殖.

abstractsObjective To investigate the effects of T-type calcium channel inhibitors (ProTx-1,micromolar Ni2+ and Mibefradil) on Monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats.Methods Forty male Sprague-Dawley rats were randomly divided into 5 groups:normal control group,MCT group,ProTx-1 group,micromolar Ni2+ group and Mibefradil group (8 cases in each group).The right ventricular systolic pressure (RVSP),the right ventricular hypertrophy index (RVHI),and the index of pulmonary vascular remodeling(MA％) were measured on day 28 after MCT-treatment.Western blot was used to detect the expression of proliferating cell nuclear antigen(PCNA) and Cleaved Caspase-3 in pulmonary artery.Results (1)RVSP and RVHI in MCT group were significandy higher than those in the other 4 groups (F =21.55,P ＜ 0.01;F =15.63,P ＜ 0.01).The two indexes in 3 intervention groups were higher than those in normal control group (all P ＜ 0.05),nevertheless,significantly lower than those in MCT group,and 3 intervention groups showed no significant differences (all P ＞ 0.05).(2) MA％ in normal control group [(23.43 ± 1.95) ％] was lower than that in MCT group [(80.42 ± 4.30) ％],ProTx-1 group [(60.35 ± 3.83)％],micromolar Ni2+ group[(62.44 ± 3.81)％] and Mibefradil group[(58.66 ± 4.23)％] (F =216.2,P ＜ 0.01);3 intervention groups showed no significant differences (all P ＞ 0.05),however,they were all significantly lower than that in MCT group.(3) The expression of PCNA in MCT group was higher than that in normal control group,meanwhile,3 intervention groups were significantly lower than that in MCT group.The expression of Cleaved Caspase-3 in MCT group was higher than that in normal control group,nevertheless,3 intervention groups showed no significant changes compared with MCT group,respectively.Conclusions T-type calcium channel inhibitors could ameliorate the progression of MCT-PAH in rats,mainly through suppressing the proliferation of pulmonary artery smooth muscle cells.