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目的观察野百合碱(MCT)诱导的肺动脉高压大鼠中花生四烯酸色素p450表氧化酶CYP2J2基因过表达时血浆和肺组织中内皮素-l(ET-1)、一氧化氮(NO)血栓素A2(TXA2)和前列腺素I2(PGI2)的水平及肺组织中一氧化氮合酶(NOS)活性的变化。方法成年雄性SD大鼠60只随机分为正常对照组(n=30)和MCT模型组(n=30),皮下注射MCT(60mg/kg)建立肺动脉高压模型。三周后尾静脉分别注射生理盐水和质粒分为6组:NS组,pCDNA3.1(n=10),pcDNA3.1-CYP2J2(n=10),MCT+NS(n=10),MCT+pCDNA3.1(n=10),MCT+pCDNA3.1-CYP2J2(n=10)。三周后,检测大鼠肺动脉压(mPAP),测定血浆和肺组织中ET-1和NO水平,检测肺组织中NOS和eNOS的活性,检测血浆和肺组织TXA2代谢产物TXB2和PGI2代谢产物6-酮-前列腺素1α(6-keto-PGF1α)水平及TXB2/6-keto-PGF1α的比值。结果 MCT模型组mPAP,血浆和肺组织中ET-1水平和TXB2含量和TXB2/6-keto-PGF1α比值均明显高于正常对照组(P<0.05),而pCDNA3.1-CYP2J2治疗组与MCT模型组比均显著降低(P<0.05),但仍高于正常对照组(P<0.05);MCT模型组血浆和肺组织中NO和6-keto-PGF1α含量,肺组织eNOS和NOS活性,TXB2/6-keto-PGF1α比值均明显低于正常对照组(P<0.05),而pCDNA3.1-CYP2J2治疗组均明显增高(P<0.05),但仍低于正常对照组(P<0.05)。结论花生四烯酸色素p450表氧化酶基因CYP2J2可逆转MCT诱导的肺动脉高压,其机制可能与降低肺组织和血浆中的ET-1和TXA2含量,升高PGI2含量,上调TXA2/PGI2比值,上调机体内eNOS和总NOS活性,增加体内NO水平有关。CYP2J2基因治疗对肺动脉高压有积极的治疗作用。
Objective To investigate the effects of endothelin-1 (ET-1) and nitric oxide (NO) in plasma and lung tissue of arachidonic acid pigment p450 epoxidase gene CYP2J2 induced by monocrotaline (MCT) TXA2 and PGI2 levels and lung tissue nitric oxide synthase (NOS) activity changes. Methods Sixty adult male Sprague-Dawley rats were randomly divided into normal control group (n = 30) and MCT model group (n = 30), and subcutaneous injection of MCT (60 mg / kg) to establish pulmonary hypertension model. Three weeks later, the tail vein was injected with normal saline and plasmid respectively into 6 groups: NS group, pCDNA3.1 (n = 10), pcDNA3.1-CYP2J2 (n = 10), MCT + NS pCDNA3.1 (n = 10), MCT + pCDNA3.1-CYP2J2 (n = 10). Three weeks later, the pulmonary arterial pressure (mPAP) of rats was measured. The levels of ET-1 and NO in plasma and lung tissue were measured. The activities of NOS and eNOS in lung tissue were measured. The TXB2 metabolites TXB2 and PGI2 metabolites in plasma and lung tissue - keto - prostaglandin 1α (6-keto-PGF1α) levels and TXB2 / 6-keto-PGF1α ratio. Results The levels of ET-1, TXB2 and TXB2 / 6-keto-PGF1α in mPAP, plasma and lung tissue in MCT model group were significantly higher than those in normal control group (P <0.05), while those in pCDNA3.1-CYP2J2 treatment group and MCT The levels of NO and 6-keto-PGF1α in plasma and lung tissue in MCT model group, the activity of eNOS and NOS in lung tissue, the level of TXB2 in model group were significantly lower than those in normal control group (P <0.05) / 6-keto-PGF1α were significantly lower than those in the normal control group (P <0.05), while those in the pCDNA3.1-CYP2J2 treatment group were significantly higher than those in the normal control group (P <0.05). Conclusion CYP2J2, an arachidonic acid pigment p450 epoxide oxidase gene, can reverse pulmonary arterial hypertension induced by MCT, and its mechanism may be related to the decrease of ET-1 and TXA2 content in lung tissue and plasma, increase of PGI2 content and up-regulation of TXA2 / PGI2 ratio The body of eNOS and total NOS activity, increased NO levels in the body. CYP2J2 gene therapy has a positive therapeutic effect on pulmonary hypertension.