Studies On The Protective Role And Pathogenesis Of Exogenous L-arginine In Liver Injury Rats

Object :To study effects of exogenous L-arginine on expression of nitric oxide synthase and on microcirculatory and hemorheology disturbance,in order to understand the protective role and pathogenesisof exogenous L-arginine in liver injury.Methods: Acute Liver injury was induced by subcutaneous injection of Thionletamide(TAA). The rats were randomly divided into 4 groups which received the following treatments:L-arg group and L-arg+TAA group were made by intragastric L-arg (100mg/kg) separately for three days, from the beginning of the fourth day, L-arg+TAA group and TAA group were made by subcutaneous injection of TAA(600mg/kg) for two days. After 48h the second injection of TAA, blood was taken from abdominal aorta carefully. Liver function was evaluated by ALT, TB,ALB and endotoxin of plasma; whole blood viscosity and platelet aggregation will demonstrate the changes of hemorheology; meanwhile the liver homogenate levels of NO,MDA,SOD were evaluated by spectrophotometric determination and thromboxanes B2 (TXB2) was detected radioimmunoassay . Weigert 's staining showed microthrombi. The expression of eNOS and iNOS in liver were detected by immunohistochemistry method.Results:The levels of NO,SOD in L-arg group significantly increased (vs N group,p<0.05) and whole blood viscosity and MaxPag(%) significantly decreased (vs other groups, p<0.05); The levels of ALT,MDA in L-arg+TAA group were not different (vs L-arg group, p>0.05); the levels of ALT,TB,endotoxin,MDA and TXB2 in L-arg+TAA group significantly decreased (vs TAA group, p<0.05), but SOD significantly increased (vs TAA group, p<0.05), whole blood viscosity and MaxPag(%) significantly decreased (p<0.05). HE showed: infiltration of inflammatory cells and necrosis did not observe and blood vessel significantly expanded in L-arg group; infiltration of inflammatory cells in L-arg+TAA group reduced and damage of hepatocytes significantly lighten(vs TAA group, p<0.05); hepatocytes inflated and sinusoidal narrowed, a large number inflammatory cells infiltrated and point or slice necrosis in TAA group.Weigert 's staining showed: Microthrombi in L-arg group was significantly decreased (vs L-arg+TAA group and TAA group , p<0.05); and microthrombi in L-arg+TAA group significantly reduced also(vs TAA group, p<0.05).Immunohistochemical staining showed: eNOS expressive upregulation in L-arg group compared with L-arg+TAA group(p<0.05) , they were localized in the plasma of hepatocytes; nevertheless iNOS expressive upregulation in TAA group compared with L-arg+TAA group(p<0.05), they were localized in plasma of hepatocytes and kupffer cells. Conclusions:Microcirculatory dysfunction exit in the couse of occurring acute liver injury, eNOS expression upregulation after treating with exogeneous L-arginine, productive NO has good antiplatelet,antithrombotic and anticoagulation effect by inhibiting platelet aggragation to diminish formation of microthrombi in liver and improve hepatic microcirculation. With increasing SOD and decreasing oxide free radical, whole blood viscosity decreased and hepatocytes were protected; but iNOS expression upregulation by subcutaneous injection of TAA, productive NO damaged to hepatocytes.