摘要
目的探讨T型钙通道阻滞剂ProTx-1、micromolar Ni^2+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 Ni^2+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 Ni^2+干预组[(62.44±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 Ni^2+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。
Objective To investigate the effects of T - type calcium channel inhibitors ( ProTx - 1, micromolar Ni^2+ and Mibefradil) on Monocrotaline (MCT) -induced pulmonary arterial hypertension (PAH) in rats. Methods Forty male Spragne - Dawley rats were randomly divided into 5 groups : normal control group, MCT group, ProTx - 1 group, micromolar Ni^2+ group and Mibefradil group (8 cases in each group ). The fight 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 Ni^2+ 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.
出处
《中华实用儿科临床杂志》
CSCD
北大核心
2017年第1期63-66,共4页
Chinese Journal of Applied Clinical Pediatrics
基金
上海市科学技术委员会科技攻关计划(12411952403)
关键词
肺动脉高压
野百合碱
电压依赖性钙通道
增殖
凋亡
Pulmonary arterial hypertension
Monoerotaline
Voltage dependent calcium channel
Proliferation
Apoptosis