NO在肝纤维化形成中对肝脏微循环的影响

The Effect of Nitric Oxide(NO)on Hepatic Microcirculation in the Development of Hepatic Fibrosis

目的探讨外源性一氧化氮 (nitricoxide ,NO)对肝脏微循环障碍的影响和在肝纤维化发生发展中的作用。方法将大鼠分为3组 :正常对照组 (normalcontrol,NC) :以正常饮食喂养 ;采用复合因素致肝纤维化组 (hepaticfibrosis,HF) :同时用生理盐水1.5ml·只 -1·d -1灌胃 ;HF +Arg组 :以肝纤维化对照组为基础 ,同时予L -精氨酸 (L-arginine,L -Arg)100mg·Kg-1·d-1灌胃。于实验4周末 ,观察血浆内毒素(lipopolysaccaride ,LPS)、NO、丙二醛 (malondialdehyde,MDA)和超氧化物歧化酶 (superoxidedismutase ,SOD)水平 ,观察各组肝组织纤维增生程度 ,用台盼蓝原位灌流肝脏来观察肝脏微循环的改变。结果血浆内毒素水平在HF组均明显高于NC组 ,HF +Arg组内毒素水平虽比NC组高 ,但差异无显著性 ;NO水平HF +Arg组明显高于HF组 ;血浆MDA水平各实验组均明显高于NC组 ;血浆SOD活性HF组明显低于NC组和HF+Arg组 ;肝脏纤维组织目标面积HF组明显大于HF +Arg组 ;用台盼蓝原位灌流肝脏发现HF组灌流时间最长 ,HF +Arg组与NC组比较差异无显著性。结论外源性NO可能通过改善肝脏微循环 ,防止肝脏缺血和炎性细胞介质诱导的氧化损伤 ,延缓肝纤维化的发展。

Objective To explore the effect of exogenous NO on hepatic microcirculatory dysfunction in the formation and development of hepatic fibrosis.Methods The wastar rats were divided into three groups,including①normal control group(NC),②hepatic fibrosis group(HF),and③HF+Arg group.NC was fed with general diet.In HF and HF+Arg groups,the hepatic fibrosis model of rats established by complex pathogens was introgasˉtric_infused with0.9%salt(1.5ml/d)and L_arginine(100mg.Kg -1 ·d -1 )respectively.At the end of4th week,the level of plasma endotoxin,NO,malondialdehyde(MDA)and superoxide dismutase(SOD)were detected,the degree of hepatic fibrosis was observed.The liver of rats was perfused with trypan_blue to observe the change of hepˉatic microcirculation.Results The level of plasma endotoxin in HF group was significantly higher than that in NC.The level of plasma endotoxin in HF+Arg group was higher than that in NC,but there was no significant difference between them.The level of plasma NO in HF+Arg group was significantly higher than that in HF.The level of plasma MDA was markedly different in experimental groups compared with NC.The level of plasma SOD in HF group was obviously lower than that in NC and HF+Arg groups.The area of hepatic collagen in HF group was sigˉnificantly larger than that in HF+Arg group.It was found that trypan_blue distribution time in HF group was the longest when the liver was perfused with trypan_blue,while there was no significant difference between HF+Arg group and NC.Conclusions The exogenous NO may prevent the hepatic ischemia and the leukocyte_induced oxidaˉtive hepatic injury by improving hepatic microcirculation,which could prevent the development of hepatic fibrosis.