环孢菌素A阻断刀豆蛋白A诱发昆明小鼠肝损害的研究

THE PROTECTIVE EFFECTS OF CYCLOSPORINE A ON CONCANAVALIN A INDUCED LIVER INJURY IN KUNMING MICE

观察环孢菌素A(CsA)能否阻断刀豆蛋白A (ConA)诱发小鼠肝损害 ,将昆明小鼠随机分为 5组 ,ConA自小鼠尾静脉注入制作肝损害实验动物模型 ,据ConA应用剂量不同而分别称为ConA 10mg/kg组 ,ConA 2 0mg/kg组和ConA 40mg/kg组 ;应用ConA前 15h和 1h皮下注射CsA(130mg/kg) ,该组称为CsA组 ;单独用PBS者为对照组。应用ConA后 8h取小鼠血测定ALT与TNF α ,并取肝组织行病理学观察。结果显示 ,ConA成功复制了小鼠特异性肝损害 ;CsA组小鼠血浆中ALT与PBS组相比无显著性差异 (P >0 .0 5 ) ,血浆TNF α亦无增高 ;病理学观察未发现肝脏内淋巴细胞及其他炎性细胞浸润。提示CsA可完全阻断ConA诱发小鼠肝损害 ,抑制T淋巴细胞活化和TNF

To investigate the possible effects of cyclosporine A(CsA) on the T cell dependent liver injury induced by Concanavalin A (Con A) in Kunming mice,25 Kunming mice were randomly divided into five groups. Con A (doses of 10mg/kg, 20mg/kg and 40mg/kg) was administered via the tail vein to duplicate the liver injury as the ConA group; CsA subcutaneously injected twice at doses of 130mg/kg 15 hours and 1 hour respectively before ConA challenge constitutes the CsA group. Phosphate buffered saline (PBS) only served as the control group. Blood samples for tumor necrosis factor alpha (TNF α) and alanine aminotransferase (ALT) measurement were obtained at 8 hours after ConA administration. Histopathological examination was also performed for liver tissue. The results showed that ConA induced specific liver injury in Kunming mice was successfully duplicated. CsA markedly protected the mice from Con A induced liver injury by comparing the levels of serum ALT(44±16U/L vs 341±52U/L, P <0.01) and histological examinations between CsA and ConA groups(40mg/kg). Pretreatment with CsA before ConA challenge also resulted in the absence of infiltration of lymphocytes in the portal area and the undetectable serum TNF α. It is concluded that CsA has the potential effect on the prevention of ConA induced liver injury by abrogating the activation of the lymphocytes and reduce the release of TNF α.