Natarajan Sathish Kumar, Basivireddy Jayasree, Ramachandran Anup, Thomas Simmy, Ramamoorthy Prabhu, Pulimood Anna B, Jacob Molly, Balasubramanian Kunissery A
Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
Hepatology. 2006 Jun;43(6):1248-56. doi: 10.1002/hep.21179.
Cirrhosis with ascites is associated with impaired renal function accompanied by sodium and water retention. Although it has been suggested that mediators such as nitric oxide play a role in the development of renal failure in this situation, other mechanisms underlying the process are not well understood. This study examined the role of oxidative stress in mediating renal damage during the development of cirrhosis in order to understand mechanisms involved in the process. It was shown that carbon tetrachloride- or thioacetamide-induced cirrhosis in rats results in oxidative stress in the kidney as seen by increased lipid peroxidation and protein oxidation, accompanied by altered antioxidant status. Cirrhosis was also found to affect renal mitochondrial function, as assessed by measurement of the respiratory control ratio, the swelling of mitochondria, and calcium flux across mitochondrial membranes. Increased lipid peroxidation and changes in lipid composition were evident in the renal brush border membranes, with compromised transport of 14C glucose across these membranes. In conclusion, renal alterations produced as a result of cirrhosis in the rat are possibly mediated by oxidative stress.
肝硬化伴腹水与肾功能受损及钠水潴留有关。尽管有研究表明一氧化氮等介质在这种情况下的肾衰竭发展中起作用，但该过程的其他潜在机制尚不清楚。本研究探讨了氧化应激在肝硬化发展过程中介导肾损伤的作用，以了解该过程涉及的机制。结果表明，四氯化碳或硫代乙酰胺诱导的大鼠肝硬化会导致肾脏氧化应激，表现为脂质过氧化和蛋白质氧化增加，同时抗氧化状态改变。通过测量呼吸控制率、线粒体肿胀和跨线粒体膜的钙通量评估发现，肝硬化还会影响肾线粒体功能。肾刷状缘膜中脂质过氧化增加和脂质组成改变明显，14C葡萄糖跨这些膜的转运受损。总之，大鼠肝硬化导致的肾脏改变可能由氧化应激介导。
