L-精氨酸预处理对肝硬化大鼠肝脏缺血再灌注损伤保护作用的实验研究  

Protective mechanism of L-arginine against liver ischemic-reperfusion injury in the rat model of liver cirrhosis

作　　者：张志强[1] 蔡兵[1] 吴鸣宇[1] 

机构地区：[1]无锡市人民医院肝胆外科,江苏无锡214023

出　　处：《肝胆胰外科杂志》2010年第1期13-17,共5页Journal of Hepatopancreatobiliary Surgery

摘　　要：目的探讨L-精氨酸(L-arginine,L-arg)预处理对硬化肝脏缺血再灌注(ischemia-reperfusion,I/R)损伤的保护作用及机制。方法采用硫代乙酰胺(thioacetamide,TAA)复制大鼠肝硬化模型,然后阻断第5叶入肝血流30 min,再灌注60 min,建立部分肝缺血再灌注模型。24只肝硬化大鼠随机分成4组(n=6):①肝硬化大鼠对照组(对照组),仅分离肝周围韧带,不进行肝门阻断及再灌注;②肝硬化缺血再灌注组(缺血再灌注组);③L-精氨酸预处理组(精氨酸组);④L-硝基精氨酸甲酯(L-nitro-arginine-methy L-ester,L-NAME)预处理组(硝基精氨酸甲酯组)。后三组分别于缺血前15 min经门静脉给予生理盐水、L-arg和L-NAME处理,测定再灌注后肝内门-体分流、血清门冬氨酸转氨酶(aspartate aminotransferase,AST)、丙氨酸转氨酶(alanine aminotransferase,ALT)、乳酸脱氢酶(lactate dehydrogenase,LDH)和肝组织超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(mal-ondialdehyde,MDA)、一氧化氮(nitric oxide,NO)、三磷酸腺苷酶(adenosine triphosphatase,ATPase)等的变化。采用门静脉连续输注山梨醇法,测定肝脏山梨醇摄取率,计算肝内门-体分流。结果缺血再灌注组与对照组比较:功能性肝血流量(functional hepatic blood flow,FHBF)、SOD显著降低(P<0.01),肝内分流率、肝内分流量(intrahepatic shunt flow,IHSF)、MDA、ALT、AST、LDH显著升高(P<0.01或P<0.05);精氨酸组与缺血再灌注组比较:NO、FHBF、SOD、Na+/K+-ATPase、Ca2+-ATPase、Mg2+-ATPase显著升高(P<0.01或P<0.05),肝内分流率、IHSF、MDA、ALT、AST、LDH显著下降(P<0.01或P<0.05);硝基精氨酸甲酯组与缺血再灌注组比较:NO、FHBF显著下降(P<0.01),IHSF、MDA显著升高(P<0.01)。结论L-arg对硬化肝脏缺血再灌注损伤有保护作用,其保护机制是通过增加肝脏内源性NO,从而减少肝内门-体分流,增加功能性肝血流以及改善细胞能量代谢而实现的。Objective To explore and investigate protective mechanism of L-arginine against liver isohemicreperfusion （I/R） injury in a rat model of liver cin＇hosis. Methods Cirrhotic rats were induced by oral administration of thioacetamide （FAA）. Tile rats underwent partial hepatic ischenlia-reperfusion. Twenty-four cirrhotic rats were randomly divided into 4 groups （n=6）. The control group was also served as the sham-operalcd control. Other three groups were subjected to 30 rain lobar ischemia and 60 rain reperfusion. Of them, groups I/R, L-arginine （L-arg） and L-NAME were preconditioned with normal saline, L-arg and l,-nitro-argi- nine-methy L-ester （L-NAME） respectively. All drugs were injected through catheters in the distal ileocolic veins, lntraportal infusion of sorbitol （10 mmol/L, 0.2 mlJmin） commenced after 60 min reperfusion, at the same time, blood sample was drawn from the jugular vein catheter for biochemistry test, suc.h as alanine aminutransferasc （AI,T）, aspallate aminotransfcrase （AST） and lactate dehydrogenase （LDH）. Two minutes after initiation of surbitol infusion, blood samples were drawn simuhaneously from the carotid artery, portal venous and hepatic venous catheters fur sorbitol concentration assay. Portal venous flow （PVF） and hepatic arterial flow （HAF） were measured via electromagnetic flow probes. Hepatic sorbitol uptake and intrahepatic shunt flow （IHSF） were calculated by PVF, HAF and sorbitol concentrations in the portal vein, hepatic vein and carotid artery. On the termination of experiments, lesion liver lobes excised for histochemical assay, such as super- oxide dismutase （SOD）, malondialdehyde （MDA）, nitric oxide synthase （NOS）, nitric oxide （NO） and ATPase. Results I/R increased intrahepatic shunting fraction, MDA in liver, decreased SOD in liver. L-arg decreased intrahepatic shunting fraction, MDA in liver, and increased SOD in liver. Conclusion The possible protective mechanism of L-arg can ameliorate cirrhotic liver, I

关 键 词：肝脏 肝硬化 缺血再灌注损伤 肝内门-体分流 一氧化氮 山梨醇 L-精氨酸 大鼠 

分 类 号：R575.2[医药卫生—消化系统]