摘要
该研究深入系统评价结扎肾血管所致急性肾损伤大鼠模型,以便于更好的掌握和应用该模型进行药物研究。采用2～3月龄雄性SD大鼠作为受试对象,以摘除左肾,结扎右肾40 min,复灌24 h方法进行造模。以血清肌酐(Crea),尿素氮(BUN)及其肾组织切片为评价肾功能的基本指标,同时表达相关炎性坏死及凋亡因子以评价其分子病生理变化的机制。结果显示结扎肾动静脉所导致的血清Crea和BUN明显持续高于单纯肾动脉结扎。大鼠肾动静脉同时结扎40 min复灌24 h后,大鼠血清Crea从小于100μmol·L-1到大于430μmol·L-1不等。其中Crea小于100μmol·L-1为1. 63%,100～200μmol·L-1为5. 43%,200～300μmol·L-1为16. 67%,大于430μmol·L-1占18. 87%,300～430μmol·L-1大鼠占动物总数的66. 3%(动物总数184只)。复灌72 h血清Crea 370～430μmol·L-1组大鼠血清Crea仍持续升高,而血清Crea 200～300μmol·L-1组和Crea 300～370μmol·L-1组大鼠血清Crea则很快恢复。无论血清Crea升高还是降低,其肾小管均出现空泡样变性甚至坏死脱落等病理反应。肾组织TLR4,TNF-α,IL-6 mRNA表达明显升高,其中以血清Crea 370～430μmol·L-1组大鼠升高最为明显。该研究结果表明结扎肾动静脉并复灌所致急性肾损伤模型具有操作简便,且血清Crea和BUN具有持续升高等特点,如此将有利于药物效应的观察。这种急性肾损伤主要与炎性坏死病生理反应相关。
In this study,in-depth systematic evaluation of rat of acute kidney injury(AKI) caused by renal arteriovenous ligation was conducted to better master and apply this model for drug research. Male SD rats of 2-3 months old were employed in this study.The left kidney was removed,and the right kidney received ligation for 40 min and reperfusion for 24 h. Serum creatinine(Crea),urea nitrogen(BUN) and the renal tissue sections were assayed as the basic indicators to evaluate their renal function. The mRNA expression of inflammatory necrosis factors and apoptotic factors was used to evaluate the mechanism of molecular pathophysiological changes. The results showed that the serum Crea and BUN caused by ligation of both renal arteries and veins were significantly higher than those of rats with renal artery ligation. After renal arteriovenous ligation for 40 min and reperfusion for 24 h in rats,the serum Crea of the rats varied from less than 100 μmol·L^-1 to more than 430 μmol·L^-1. Among them,5 rats showed less than 100 μmol·L^-1 serum Crea,20 rats with 100-200 μmol·L^-1 serum Crea and 12 rats with more than 430 μmol·L^-1. Rats with serum Crea between 300-430 μmol·L^-1 accounted for 66.3%(122/184) of the total number of the experiment rats. After 72 h reperfusion,serum Crea in the group of Crea 370-430 μmol·L^-1 continued to increase,while the serum Crea in the group of Crea 200-300 μmol·L^-1 and the group of Crea 300-370 μmol·L^-1 recovered quickly. No matter serum Crea was elevated or decreased,the renal tubules showed pathological changes such as vacuolar degeneration or even necrosis. The mRNA expression levels of Toll-like receptor(TLR4),tumor necrosis factor(TNF-α) and interleukin(IL-6) in renal tissueswere significantly up-regulated,and the effect was most obvious in the group of serum Crea 370-430 μmol·L^-1. The study indicated that the model for AKI caused by renal arteriovenous ligation and reperfusion is easy to operate,and the serum Crea and BUN have the characteristics of continuous increase,beneficial to the observation of drug effects. This acute kidney injury is mainly related to the pathophysiological response of inflammatory necrosis.
作者
龚琴
王木兰
左沙沙
张远利
许溪
何鹿玲
冯育林
杜力军
李俊
GONG Qin;WANG Mu-lan;ZUO Sha-sha;ZHANG Yuan-li;XU Xi;HE Lu-ling;FENG Yu-lin;DU Li-jun;LI Jun(Jiangxi University of Traditional Chinese Medicine,Nanchang 330006,China;State Key Laboratory of Innovative Drugs and Efficient Energy-saving Pharmaceutical Equipment,Jiangxi University of Traditional Chinese Medicine,Nanchang 330006,China;School of Life Sciences,Tsinghua University,Beijing 100084,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2019年第5期996-1003,共8页
China Journal of Chinese Materia Medica
基金
国家"重大新药创制"科技重大专项(2018ZX09301030-002)
关键词
大鼠
肾缺血复灌
急性肾损伤
动静脉结扎
炎性反应
rats
renal ischemia reperfusion
acute kidney injury
arteriovenous ligation
inflammatory reaction
