姜黄素对百草枯中毒大鼠急性肾氧化损伤的干预作用

摘要

Objective:To investigate the effect of curcumin on oxidative stress of acute renal injury in rats induced by paraquat and the mechanism underlying its effect. Methods:Sixty rats were randomly divided into 4 groups:control group (n=15), curcumin control group (curcumin 50 mg/kg) (n=15), PQ poisoned group (2%paraquat solution 100 mg/kg) (n=15), and curcumin intervention group (intraperitoneal injection of curcumin 50 mg/kg at 15 min, 24 h, or 48 h after paraquat exposure) (n=15). On days l, 3 and 7 after the treatment and renal tissue was collected. The content of malonaldehyde (MDA) and glutathione (GSH), the activities of superoxide dismutase activity (SOD) and catalase (CAT) in the renal tissue were determined with chemical colorimetry. The activities of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) in the renal tissue were determined with ELISA. The mRNA and protein levels of nuclear related factor 2 (Nrf2) were determined with RT-PCR and Western Blot, respectively. The pathological changes of renal tissue were examined under optical microscopy. Results:Both PQ group and curcumin intervention group with each time showed increase in MDA content, decrease in GSH content, decrease in SOD and CAT activities, increase in iNOS activities, increase in the protein and mRNA levels of Nrf2, increase in HO-1 activities at day 1, 3, in comparison with the control group (P<0.05). In comparison with the PQ group on the same day, the curcumin intervention group showed de-crease in MDA content, increase in the activities of GSH, SOD, CAT, decrease in iNOS activities, and increase in the mRNA and protein levels of Nrf2 on days l, 3 and 7, increase in HO-1 on days 1, 3 (P<0.05). In the PQ group, the clearance of glomerulus saccules was increased, arranged in disorder, renal tubular epithelial cell ap-peared glassy degeneration and vacuolar degeneration with time expanding, but compared with PQ group, the pathological manifestations was relieved obviously with the same time in the curcumin intervention group. Con-clusion:Curcumin plays a protective role in paraquat poisoning with oxidative stress of acute renal injury, which may depend on inducing the expression of Nrf2, increasing the HO-1, SOD and other antioxidant enzyme levels, and increasing the ability of resistance to oxidative stress in renal tissue.%目的：探讨姜黄素对百草枯（PQ）中毒大鼠急性肾氧化损伤的干预和可能机制。方法：将60只SD大鼠随机分为正常对照组15只、姜黄素对照组（姜黄素50 mg/kg）15只、PQ染毒组（PQ 100 mg/kg）15只、姜黄素干预组（PQ染毒后15 min、24 h、48 h，腹腔注射姜黄素50 mg/kg）15只。大鼠经处理后第1、第3、第7天取肾组织，化学比色法检测肾组织匀浆液丙二醛（MDA）和谷胱甘肽（GSH）含量，超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活力；ELISA法检测血红素氧合酶-l（HO-1)、诱导型一氧化氮合酶（iNOS）活力；RT-PCR法检测核转录相关因子2（Nrf2）mRNA表达，Western Blot法检测Nrf2蛋白表达。光学显微镜下观察肾组织的病理变化。结果：与正常对照组比较，PQ染毒组和姜黄素干预组各时间点MDA含量均升高， GSH、SOD、CAT活力均降低，iNOS活力升高，Nrf2 mRNA和蛋白表达均升高，第1、第3天HO-l活力升高，差异均有统计学意义（均P＜0.05）；与同时间点PQ染毒组比较，姜黄素干预组各时间点MDA含量明显降低， GSH、SOD、CAT明显升高，iNOS活力下降，Nrf2 mRNA和蛋白表达明显升高，第1、第3天HO-1活力升高（P＜0.05）；PQ染毒组肾小球球囊间隙增大，排列紊乱，随时间延长，肾小管上皮细胞出现玻璃样变性及空泡样变性，姜黄素干预组病理表现较PQ染毒组明显减轻。结论：姜黄素对PQ中毒大鼠急性肾氧化损伤有保护作用，其机制可能是通过诱导肾组织Nrf2表达，上调HO-1、SOD等抗氧化酶水平，提高肾组织抗氧化应激能力。