Effect And Mechanism Of Rhein On Liver Injury Rats

Object: To study the protective role and pathogenesis of Rhein in liver injury.Methods: Acute liver injury was induced by intragastric Thionletamide(TAA). The rats were randomly devided into 3 groups which received the following treatments: TAA+RH group was made by intragastric RH(30mg/kg) for four days, from the beginning of the third day, TAA group and TAA+RH group were made by intragastric TAA(250 mg/kg), and it was repeated 24 hours later. After another 24h, blood was taken from abdominal aorta carefully. ALT,LDH,TB endotoxin of plasma and the liver homogenate levels of thromboxanes B2(TXB2),6-keto-PGF1α,endothelin-1 ,NO were detected; whole blood viscosity and platelet aggregation will demonstrate the changes of hemorheology. HE show histomorphology and Weigert's staining showed microthrombi. The expression of CD14 and eNOS and iNOS in liver were detected by immunohistochemistry method.Results:1. The levels of ALT,LDH,TB,endotoxin ,NO ,TXB2 and whole blood viscosity and MaxPag(%)in TAA+RH group significantly decreased(vs TAA group, p<0.05 or p<0.01),nevertheless the levels of 6-keto-PGF1αsignificantly increased(p<0.05).2.HE showed:Hepatocytes point or slice necrosis and a large number of inflammatory cells infiltrated in TAA group; infiltration of inflammatory cells reduced and damage of hepatocytes significantly lightened in TAA+RH group.3.Weigert's staining showed: A large number of blue fifiform ball microthrombi could be seen in TAA group, microthrombi in TAA+RH group significantly reduced (vs TAA group, p<0.01).4.Immunohistochemical staining showed: CD14 expression downregulation in TAA+RH group compared with TAA group(p<0.01); iNOS expression downregulation in TAA+RH group compared with TAA group(p<0.05); eNOS expression upregulation in TAA+RH group and RH group respectively compared with TAA group and Normal group(p<0.01). Conclusion: Intestinal endotoxmia exited in TAA-induced liver injury and IETM induced severe hepatic microcirculatory and hemorheology dysfunction. RH could decrease levels of endotoxin and downregulate expression of the endotoxin receptor protein CD14 to antagonize biologic effects of endotoxmia. At the same time, RH could increase physiological NO by regulating expression of iNOS and eNOS to improved endotoxmia-induced microcirculatory and hemorheology dysfunction.