L-精氨酸诱导大鼠暴发性胰腺炎肝损伤的实验研究

Study on Fulminant Acute Pancreatitis-associated Liver Injury Induced by L-arginine in Rats

目的:建立L-精氨酸诱导大鼠暴发性胰腺炎(FAP)肝损伤模型,并探讨FAP肝损伤机制。方法:L-精氨酸分次间隔2h分别于腹腔和皮下注射。末次注射后观察120 h内大鼠死亡率以及6、12、24、48、72和120 h血清淀粉酶、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)以及门静脉血中肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)含量变化;同时观察各时点胰腺、肝脏病理改变及肝细胞凋亡变化。结果:注射后大鼠120 h内死亡率为53.33%;AST、ALT、TBIL、IL-6、TNF-α于6 h升高,其中AST、TBIL、IL-6于24 h达高峰,ALT、TNF-α于48 h达高峰;胰腺、肝脏病理改变以及肝细胞凋亡均于6 h开始变化,48 h达高峰。结论:大剂量L-精氨酸可诱导大鼠FAP肝损伤模型,TNF-α、IL-6、细胞凋亡可能参与其损伤机制。

Objective： To establish the model of fulminant acute pancreatitis（ FAP）-associated liver injury induced by L-arginine in rats, and to study the mechanism of hepatic lesion in the model. Methods： Male rats were given intraperitoneal and subcutaneous injection with L-arginine for 2 times at an interval of 2 hours. After injection, the mortality of rats within 120 hours was observed. At the point of 6, 12, 24, 48, 72 and 120 hours, the serum amylase（AMS）, alanine aminotraferase（ALT）, aspartate aminotrferase（AST）, total bilirubin（TBIL）, tumor necrosis factor（TNF）-α, interleukin（IL）-6 were tested; the pathological changes of pancreas and liver were observed; and the hepatocytes apoptosis was analyzed. Results： After injection of L-arginine, the mortality of rats within 120 hours was 53.33%; AMS, ALT, AST, TBIL, TNF-α, IL-6 were all increased at 6 hours, and peaked at 24, 48, 24 , 24, 48 , 24 hours individually. The pathological alteration of pancreas and liver appeARed at 6 hours and peaked at 48 hours. The hepatocytes apoptosis was increased at 6 hours, and reached the top at 48 hours. Conclusion： The administration of L-arginine can induce the model of FAP-associated liver injury in rats, and the mechanism of injury may be related to TNF-α, IL-6 and cells apoptosis.