L-精氨酸和牛磺酸联合抗缺氧损伤及防治缺氧性肺动脉高压的研究

Protection against hypoxic injury and amelioration of hypobaric hypoxic pulmonary hypertension by treating with L-arginine combined taurine in rats

目的研究L-精氨酸、牛磺酸联合应用的抗缺氧损伤以及对缺氧性肺动脉高压(HPH)的防治效果。方法雄性W istar大鼠40只,制作缺氧性HPH模型,随机分为平原对照组(C)、单纯缺氧组(H)、缺氧+L-精氨酸组(Arg)、缺氧+牛磺酸组(Tau)、缺氧+牛磺酸+L-精氨酸组(TA),测定各组的肺动脉压(mPAP)、右心室肥大指数(RVH I)、血浆乳酸脱氢酶(LDH)、脂质过氧化产物丙二醛(MDA)、肺匀浆NO含量的变化。结果H组与C组相比,mPAP高出约25 mmHg(P<0.01),RVH I增加1.56倍(P<0.01),血浆LDH活性增高10.1倍(P<0.01),血浆MDA含量增加1.64(P<0.01),而肺匀浆NO含量降低68%(P<0.01)。各治疗组与H组相比,mPAP均显著降低5 mmHg(P<0.05),RVH I均显著降低20%(P<0.01),血浆LDH活性显著降低(P<0.01),其中TA组与Arg组比较有显著差异(P<0.01),血浆MDA含量显著降低(P<0.01),但各治疗组之间无显著性差异。肺匀浆NO含量在Tau组无显著性变化,在Arg和TA组显著回升(P<0.01)。结论L-精氨酸和牛磺酸具有抗缺氧损伤及防治肺动脉高压的效果,两者联用可进一步增加NO产生,减少乳酸脱氢酶的漏出,加强细胞保护作用。

Objective Exposure to hypoxia induces hypoxic pulmonary hypertension （ HPH ） , the effects of taurine （Tau） and L-arginine （Arg） , and their combination （TA） on prevention against HPH were investigated. Methods Adult male Wistar rats were divided into two groups： sea level control group （C） and hypoxia group, and the hypoxia group was divided into three subgroups further, namely hypoxia control （H） , Tau, Arg and TA group. The therapy groups were given corresponding drugs every day orally. After exposed for 2 weeks in a hypobarie ehamber at simulated high altitude of 5 000 meters, the effeets of the above drugs were evaluated. Results The rats of H group developed remarkable HPH and right ventricle hypertrophy （ RVH ）, with an elevated mean pulmonary artery pressure （mPAP） of about 25 mmHg above and the right ventricular hypertrophy index （RVHI） of 1.56 folds higher （ P 〈 0. 01 ）, The activity of lactic dehydrogenase （LDH） and level of malondialdehyde （MDA） in the plasma of H group were 10. 1 and 1.64 folds higher than those of respective control groups （P〈0. 01 ） , while the NO production in the lung tissue of H group was 68% lower than that of C group （P〈0. 01 ）. The development of HPH and RVH was ameliorated in the groups with the above drugs administered respectively, with about 5 mmHg of mPAP below （ P 〈 0.05 ）, and RVHI about 20% lower than those of H group （ P 〈 0. 01 ）. The activity of LDH in each therapy group showed markedly decreases （P 〈 0.01 ,TA vs Arg, P 〈 0.01 ）, and the levels of MDA also showed significant decreases （P 〈 0. 01 ）. NO productions in the lung tissues resumed of Arg and TA groups （P 〈 0. 01 ）. Conclusion The results suggest that taurine, L-arginine and their combinaion exert cytoproteetive effects on hypoxie injury, inhibit lipidperoxidation, mitigate hypoxie pulmonary hypertension and reduce right ventricle hypertrophy.