花生四烯酸细胞色素p450表氧化酶基因对野百合碱诱导大鼠肺动脉高压的治疗作用  

The protective role of cytochrome P450 epoxygenase gene in pulmonary hypertension induced by Monocrotaline

作　　者：汪璐芸[1] 刘柳[1] 左萍[1] 张腊喜[1] 萧斌[1] 汪道文[1] 

机构地区：[1]武汉市华中科技大学同济医学院附属同济医院高血压研究所 心血管内科,430030

出　　处：《中国分子心脏病学杂志》2007年第4期218-222,共5页Molecular Cardiology of China

基　　金：国家863项目(2004AA217060);教育部博士点基金资助

摘　　要：目的研究过表达花生四烯酸细胞色素p450表氧化酶基因CYP2J2对野百合碱(MCT)诱导的大鼠原发性肺动脉高压的治疗作用,并对其机制进行初步探讨。方法模型组18只雄性大鼠一次性注射MCT(60 mg/kg·w),对照组18只。三周后分六组:MCT+生理盐水(n=6),MCT +pCB6(n=6),MCT+pCB6-2J2(n=6),生理盐水(n=6),pCB6(n=6),pCB6-2J2(n=6)。两周后,测右室收缩压RVSP和右室肥厚指数RV/(LV+s),western blot检测CYP2J2、Smad4蛋白的表达。结果模型组注射生理盐水、pCB6组RVSP分别为(41.48±0.45)和(38.13±3.68)mm Hg,显著高于正常对照组动物(20.89±3.09)mm Hg,(P<0.05)和模型组注射pCB6-2J2组(29.48±5.67)mm Hg,(P<0.05)。模型组注射生理盐水、pCB6组RV/(LV+S)分别为(0.425±0.08)和(0.358±0.07)显著高于正常对照组动物(0.24±0.03)(P<0.01)和模型组注射pCB6-2J2组(0.28±0.02) (P<0.05)。Western blots显示模型组注射生理盐水、pCB6组Smad4蛋白表达水平均明显低于注射pCB6-2J2组。结论过表达CYP2J2基因显著缓解野百合碱诱导的大鼠肺动脉高压,降低右室收缩压和减轻右心室肥厚程度,上调了TGFβ信号通道中的Smad4蛋白。Objective To assess the effect of Arachidonic acid （AA） cytochrome P450 （CYP） epoxygenase CYP2J2 gene on primary puhnonary hypertension induced by monocrotaline（MCT） and explore the mechanisms. Methods MCT（60 mg/kg·w） were injected to 18 SD rats, another 18 rats were set as control. Three weeks later, rats were assigned to six groups： MCT＋ NS （n=6）, MCT＋ pcb6 （n =6）, MCT＋pcb6-2J2 （n=6）, NS （n=6）, pcb6 （n=6）, pcb6-2J2 （n=6）. Hemodynamic data were measured and right ventricle hypertrophy were evaluated. The expression of CYP2J2 and smad4 was probed. Results RVSP is increased in the animals receiving MCT alone （41.48±0.45 mm Hg） or MCT plus pCB6 （38.13±3.68 nnn Hg） , significantly than normal control animals （20.89±3.09 mm Hg, P 〈 0.05 ） ; However, pCB6-2J2 treatment significantly attenuated the pulmonary hypertension induced by MCT （29.48 ± 5.67 nnn Hg, P 〈0.05 versus MCT ＋ pcb6 and MCT, respectively）. RV/（ 1N ＋ S） shows that rats receiving MCT either with or without pCB6 developed RV hypertrophy, with an increase in RV/（ LV ＋ S） to 0. 425 ±0.08 and 0. 358 ±0.07, respectively （ P 〈 0.01 vs normal animals）. CYP2J2 treatment attenuated the development of RV hypertrophy （index of RV hypertrophy： 0.28 ±0.02, P 〈0.05 vs. MCT ＋ pCB6 and MCT, respectively）. Western blots show that smad4 expression level significantly reduced ＇after MCT exposure, but pCB6-2J2 treatment markedly upregulated smad4 expression. Conclusion Over expression of the CYP2J2 gene attenuated the pulmonary hypertension induced by MCT, reduced RVSP and RV/（ LV ＋ S） significantly and upregulated the protein smad4 of TGFβ signaling transduction pathway.

关 键 词：花生四烯酸p450表氧化酶 CYP2J2 肺动脉高压 基因治疗 SMAD4 

分 类 号：R543.2[医药卫生—心血管疾病]