牛磺酸对百草枯中毒大鼠肾损伤的作用及机制研究

Effect of taurine on kidney injury induced by paraquat poisoning in rats

目的:探讨不同剂量牛磺酸对百草枯中毒大鼠肾脏氧化应激和炎症反应的影响。方法:选取48只雄性SD大鼠随机分为阴性对照组、百草枯染毒组、百草枯染毒+小剂量牛磺酸组和百草枯染毒+大剂量牛磺酸组。采用生化检测仪检测大鼠血清肌酐及尿素氮水平;比色法检测血标本中丙二醛(malondialdehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)水平评估氧化应激状态;另以ELISA法检测血标本中IL-6及细胞间黏附分子1(ICAM-1)水平评估炎症反应;DHE荧光探针检测肾脏活性氧簇(reactive oxygen species,ROS)水平;Western blot法检测大鼠肾脏标本丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)中p-P38 MAPK、p-JNK和pERK1/2的蛋白水平;并以real-time PCR法检测大鼠肾脏内TNF-α、TGF-β1及IL-6的mRNA水平。结果:百草枯中毒大鼠血清肌酐及尿素氮增高,牛磺酸干预后降低了中毒大鼠的肌酐及尿素氮水平,且大剂量牛磺酸组的肌酐及尿素氮水平更低。牛磺酸的干预不仅明显减轻了肾脏组织的氧化应激与炎症反应,同时也降低了百草枯中毒大鼠肾脏的MAPK活性。结论:牛磺酸干预能减轻百草枯中毒大鼠的肾损伤,其作用机制可能与下调了肾脏MAPK活性、减轻了肾脏氧化应激及炎症反应有关。

AIM ： To study the effects of taurine at different doses on renal oxidative stress and inflammation induced by paraquat in rats. METHODS： Male SD rats （n =4 8） were randomly divided into 4 groups： negative control group, paraquat group, paraquat ＋ low-dose taurine group, and paraquat ＋ high-dose taurine group. The serum levels of creatinine and urea nitrogen were detected by a biochemical analyzer. The levels of malondialdehyde （MDA） and superox-ide dismutase （SOD） were measured by colorimetry. The plasma concentrations of IL-6 and intercellular adhesion molecule （ICAM）-1 were detected by ELISA. Renal reactive oxygen species （ ROS） was checked by fluorescence probe dihydro- ethidium （DHE）. The protein levels of renal p-P38 MAPK, p-ERKl/2 and p-JNK were determined by Western blot. The mRNA expression of TNF-a, IL-6 and TGF-pl was detected by real-time PCR. RESULTS ： Serum creatinine and urea ni-trogen increased after paraquat poisoning, and decreased after feeding with taurine in poisoned rats, with better result in high-dose taurine group. Taurine reduced the oxidative stress and inflammation in the renal tissue, and also reduced the protein levels of p-JNK, p-ERKl/2 and p-P38 in the kidney of paraquat-poisoned rats. CONCLUSION： Taurine attenu-ates renal injury induced by paraquat poisoning in rats. The mechanism may be related to reducing renal MAPK activity, oxidative stress and inflammatory response.