摘要
目的探究姜黄素(curcumin,CUR)对对乙酰氨基酚(acetaminophen,APAP)诱导的大鼠急性肾损伤的保护作用及机制。方法48只雄性SD大鼠随机均分为正常组、模型组、阳性药NAC组、CUR低(50 mg/kg)、中(100 mg/kg)、高(200 mg/kg)剂量组。NAC及CUR灌胃给药10 d后,一次性灌胃给予2 g/kg APAP建立急性肾损伤模型,造模24 h后,取血并分离大鼠,计算肾指数;检测血清肌酐(Cr)、尿素氮(BUN)水平;HE染色评价大鼠肾病理变化;检测大鼠肾组织谷胱甘肽(GSH)、总超氧化物歧化酶(T-SOD)、过氧化氢酶(CAT)活性及丙二醛(MDA)水平;Western blot检测大鼠肾组织Trx-1、TXNIP、NLRP3炎症小体等蛋白的表达水平。结果与正常组相比,模型组大鼠肾指数显著增加(P<0.01),血清Cr、BUN水平显著升高(P<0.01),病理切片显示大鼠肾组织出现明显的损伤,大鼠肾组织中GSH、T-SOD、CAT的活性显著降低(P<0.01),MDA的含量显著升高(P<0.01),大鼠肾组织中Trx-1的表达明显下调(P<0.05),TXNIP、NLRP3、ASC、Cleaved caspase-1、mature IL-1β蛋白的表达明显上调(P<0.01)。与模型组相比,CUR中、高剂量组肾指数显著降低(P<0.01),病理损伤改善,血清Cr、BUN水平显著降低(P<0.01),肾组织中GSH、T-SOD、CAT活性显著升高,MDA含量显著降低(P<0.05或P<0.01),Trx-1的表达明显上调(P<0.05或P<0.01)、TXNIP、NLRP3、ASC、Cleaved caspase-1、mature IL-1β蛋白表达明显下调(P<0.01)。结论姜黄素预防性给药通过调控Trx-1/TXNIP/NLRP3通路减轻APAP诱导的大鼠急性肾损伤。
ObjectiveTo explore the protective effect and mechanism of curcumin(CUR)on acetaminophen(APAP)-induced acute kidney injury in rats.MethodsForty-eight male SD rats were randomly divided into normal,model,positive,CUR low(50 mg/kg),medium(100 mg/kg),and high(200 mg/kg)dose group.After intragastric administration of N-acetylcysteine(NAC)and CUR for 10 days,acute kidney injury models were established by intragastric administration of 2 g/kg APAP.After 24 hours,blood was collected and kidneys were collected,the kidney index was calculated,the levels of serum creatinine(Cr)and blood urea nitrogen(BUN)were measured.Pathological injury of the kidney was evaluated by HE staining,activities of glutathione(GSH),total superoxide dismutase(T-SOD),and catalase(CAT),and the malondialdehyde(MDA)level in kidneys were assessed.Expression of Trx-1,TXNIP,and NLRP3 inflammasome in kidneys was detected by Western blot.ResultsCompared with the normal group,the kidney index and the levels of serum Cr and BUN in the model group were increased significantly(P<0.01),pathological sections showed obvious lesions in the kidney,activities of GSH,T-SOD,and CAT in kidneys were significantly decreased(P<0.01),the MDA content was significantly increased(P<0.01),Trx-1 expression in the kidney was significantly decreased(P<0.05),and expression of TXNIP,NLRP3,ASC,Cleaved caspase-1,and mature IL-1βwas significantly upregulated(P<0.01).Compared with the model group,the kidney index in CUR medium,and high dose groups was significantly decreased(P<0.01),pathological damage had improved,levels of serum Cr and BUN were decreased(P<0.01),activities of GSH,T-SOD,and CAT in the kidney were increased,MDA content was decreased(P<0.05 or P<0.01),Trx-1 expression was significantly increased(P<0.05 or P<0.01),and expression of TXNIP,NLRP3,ASC,Cleaved caspase-1,and mature IL-1βprotein was significantly downregulated(P<0.01).Conclusions CUR pretreatment alleviates acetaminophen-induced acute kidney injury by regulating the Trx-1/TXNIP/NLRP3 signaling pathway in ra
作者
雷欢
桂颖
邓琴
刘子源
张维
梅之南
徐凌云
LEI Huan;GUI Ying;DENG Qin;LIU Ziyuan;ZHANG Wei;MEI Zhinan;XU Lingyun(School of Life Science and Technology,Wuhan Polytechnic University,Wuhan 430023,China;School of Pharmaceutical Science,South-Central University for Nationalities,Wuhan 430074)
出处
《中国比较医学杂志》
CAS
北大核心
2023年第3期59-65,共7页
Chinese Journal of Comparative Medicine
