肝细胞生长因子在正常和轻型急性胰腺炎小鼠的药动学研究

目的:研究肝细胞生长因子(HGF)在轻型急性胰腺炎(MAP)小鼠的药动学及胰腺分布。方法:于正常小鼠背部皮下注射125I-HGF80ng,注射后1、2、3、4、5、10、15、30、60、90、120、180、240、300min分别取血清及胰腺组织,测定HGF含量,计算HGF半减期;小鼠分为对照组和模型组,以雨蛙肽100μg/kg体重腹腔注射复制MAP模型,125I-HGF给药后30、60、120、180、360min测定血清及胰腺组织HGF含量,计算HGF半减期。结果:HGF在正常小鼠血液及胰腺组织中呈先快后慢的代谢特征,后期半减期约为130min;复制MAP后HGF在模型组小鼠血液中的后期半减期约为195min,较对照组延长(P<0.01);模型组胰腺HGF含量高于对照组(P<0.01)。结论:HGF在正常小鼠血液及胰腺中均呈先快后慢的代谢特征;MAP后HGF半减期延长,胰腺中的HGF含量增高。

The pharmacokinetics of hepatocyte growth factor in the mice with mild acute pancreatitis

Objective To investigate the pharmacokinetics and the pancreas distribution of hepatocyte growth factor (HGF) after subcutaneous administration in the pancreas in mild acute pancreatitis mice. Methods 125I-HGF was subcutaneously injected in the normal mice, then the sera and the pancreas were harvested to measure the HGF concentration at different time after the HGF administration. 125I-HGF was subcutaneously injected after abdominally injecting cerulein to induce mild acute pancreatitis while normal saline injection as control, and then the sera and the pancreas were harvested to measure the HGF concentration at different time after the HGF administration. Results HGF demonstrated a similar pharmocokinetic model as "fast followed by slow" in the normal mice and the mild acute pancreatitis mice. The half-life of HGF at late metabolic stage in the mild acute pancreatitis mice was longer than that in the normal or control mice(P<0.01). The HGF level of the pancreas in the mild acute pancreatitis mice was higher than that in the control mice. Conclusions The pharmocokinetic models of HGF share the same "fast followed by slow" type in the normal mice and the mild acute pancreatitis mice. The clearance of HGF from blood becomes slower in the mild acute pancreatitis mice. The HGF level in the pancreas of the mild acute pancreatitis mice gets higher.