内毒素引起阻塞性黄疸大鼠肾功能障碍的机制

Mechanism of plasma endotoxin on renal dysfunction in rat models with obstructive jaundice

目的探讨阻塞性黄疸(obstructive jaundice,OJ)时内毒素引起肾功能障碍的机制。方法SD大鼠60只,胆总管结扎后,分5 d(B1),10 d(B2),15 d(B3)三组,每组各10只,同时建立相应对照组(A1,A2,A3),另30只胆总管结扎后分3组(SHUD,LAC,NS),每组各10只,分别用2 ml舒胆合剂、乳果糖液、生理盐水灌胃,连用9 d。观察内毒素、血和肾组织中内皮素(endothelin,ET)、一氧化氮(nitric oxide,NO)的含量、一氧化氮合酶(nitric oxide synthase,NOS)活性及肝、肾功能的变化。结果血内毒素与血、肾组织ET含量,ET/NO比值呈显著正相关(P<0.05,r=0.630,0.438,0.496,0.453),与肌肝清除率(creatinine clearance,Ccr)和肾皮质血流量(renalcortical blood flow,BCBF)呈显著负相关(P<0.05,r=-0.600,-0.410)。血、肾组织ET/NO比值与Ccr,RCBF呈显著负相关(P<0.05,r=-0.449,-0.558,-0.626,-0.731)。血和肾组织内NO水平与内毒素水平呈负相关(P<0.05,r=-0.518,-0.441),与Ccr、RCBF呈正相关(P<0.05,r=0.422,0.496,0.400,0.659)。SHUD组与LAC血内毒素、ET水平组明显降低,血和肾组织NO,NOS活性以及Ccr,RCBF较NS组明显升高。结论OJ时内毒素可通过刺激ET的释放,提高ET/NO比值,使肾内缩血管因子与扩血管因子比例失调而损伤肾功能。

Objective To investigate the role of plasma endotoxin on renal dysfunction in rats with obstructive jaundice （O J）. Methods Sixty rats were divided randomly into 2 groups, i.e., bile duct ligated （B group） and sham operation （A group）. The former was then subdivided into five-day group （BI）, ten-day group （B2） and fifteen-day group （B3） with 10 rats in each group. The latter was also subdivided into three groups （A1 ,A2,A3） as above. Meanwhile, thirty rats with ligated bile duct were at random divided into saline group（NS）, lactulose group （LAC） and Shudan-mixture group （SHUD）. 2 ml saline was administered into rats, 2 ml lactulose and 2 ml Shudan-mixture via gastric tube respectively for nine days since the second day after bile duct ligation. The renal and liver function ,the level of endotoxin, endothelin （ET）,nitric oxide （NO） and the activity of nitric oxide synthase （NOS） were observed in each group. Result Endotoxin was positively correlated with ET,ET/NO in plasma and renal tissue（P〈0.05 ,r= 0.630,0.438,0.496,0.453 ）, while negatively correlated with Ccr, RCB F （P〈0.05, r=-0.600, -0.410 ）. The ratio of ET and NO （ET/NO）in plasma and renal tissue were negatively correlated with Ccr,RCBF（P〈0.05 ,r=-0.449,-0.558,- 0.626,-0.731 ）. The levels of NO in plasma and renal tissue were negatively correlated with endotoxin（P〈0.05,r=- 0.518, -0.441 ）, but positively correlated with Ccr, RC BF （P〈0.05, r=-0.422,0.496,0.400,0.659 ）. The levels of endotoxin and endothelin in lactulose group and Shudan-mixture group were significantly lower than that in saline group. The Ccr, RCBF and the level of NO, NOS were significantly higher in lactulose group and Shudan-mixture group than those in saline group. Conclusion The level ofendotoxin obviously increases in obstructive jaundice,which can result in elevating levels of ET and reducing level of NO in plasma and renal tissue. The increased ratio of ET/NO may be one of the main causes of renal dysfunction in obstructive jaundice.