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目的观察花生四烯酸色素p450表氧化酶基因CYP2J2过表达对野百合碱(MCT)诱导的肺动脉高压大鼠炎症细胞因子IL-6、IL-8、CRP和TNF-α表达的影响,探讨CYP2J2作用于肺动脉高压的机制。方法 :选取8周龄250-280gSD大鼠60只随机分为正常对照组(n=30)和模型组(MCT组)(n=30),模型组注射野百合碱(60mg/kg)造模。三周后分为6组:NS组(n=10),pCDNA3.1(n=10),pCDNA3.1-CYP2J2(n=10),MCT+NS(n=10),MCT+pCDNA3.1(n=10),MCT+pCDNA3.1-CYP2J2(n=10),注射质粒三周后,检测大鼠平均肺动脉压(mPAP),计算右心肥大指数(RVHl=RV/LV+S)。ELISA法检测大鼠血清中IL-6、IL-8、CRP和TNF-α水平。RT-PCR检测大鼠肺组织中IL-6和IL-8的mRNA表达。结果 :模型对照组mPAP、RVHI值、血清IL-6、IL-8、CRP和TNF-α水平及肺组织中IL-6和IL-8的mRNA表达均显著增高,与正常对照组相比有显著性差异(P<0.01);pCDNA3.1-CYP2J2治疗组mPAP、RVHI值、血清IL-6、IL-8、CRP和TNF-α水平及肺组织中IL-6和IL-8的mRNA表达均明显下调(P<0.05),但仍高于正常对照组(P<0.05)。结论花生四烯酸色素p450表氧化酶基因可通过抑制MCT诱导大鼠肺动脉高压模型中肺组织炎性细胞因子的表达、下调大鼠炎性细胞因子的分泌达到对肺动脉高压的治疗作用。
Objective To investigate the effects of CYP2J2 gene on the expression of inflammatory cytokines IL-6, IL-8, CRP and TNF-α in monocrotaline-induced pulmonary hypertension rats induced by monocrotaline (MCT) Mechanism of action on pulmonary hypertension. Methods: Sixty 250-280 g SD rats of 8 weeks old were randomly divided into normal control group (n = 30) and model group (MCT group) (n = 30). Model group was given monocrotaline (60 mg / kg) . Three groups were divided into 6 groups: NS group (n = 10), pCDNA3.1 (n = 10), pCDNA3.1-CYP2J2 (n = 10), MCT + NS (n = 10), MCT + pCDNA3.1 (n = 10) and MCT + pCDNA3.1-CYP2J2 (n = 10). The rats were injected with plasmid for three weeks. Mean pulmonary arterial pressure (mPAP) was measured and RVHl RV / LV + S was calculated. Serum levels of IL-6, IL-8, CRP and TNF-α were detected by ELISA. The mRNA expression of IL-6 and IL-8 in rat lung tissue was detected by RT-PCR. Results: The levels of mPAP and RVHI, the levels of IL-6, IL-8, CRP and TNF-α in serum and the mRNA expressions of IL-6 and IL-8 in lung tissues of model control group were significantly higher than those in normal control group (P <0.01). The levels of mPAP and RVHI, the levels of IL-6, IL-8, CRP and TNF-α in serum and the mRNA expressions of IL-6 and IL-8 in lung tissue in pCDNA3.1-CYP2J2 treatment group (P <0.05), but still higher than the normal control group (P <0.05). Conclusions Arachidonic acid p450 epoxide oxidase gene can inhibit the pulmonary inflammation in rats with MCT-induced pulmonary hypertension by down-regulating the secretion of inflammatory cytokines in pulmonary hypertensive rats.