摘要
背景:及时、有效地控制轻症急性胰腺炎可防止其向重症急性胰腺炎演变,因而具有重要的临床价值。近年来,肝细胞生长因子(HGF)能否减轻啮齿动物的急性胰腺炎正日益受到关注。目的:观察外源性HGF能否减轻小鼠轻症急性胰腺炎,并探讨其作用机制。方法:以雨蛙肽腹腔注射诱发小鼠轻症急性胰腺炎,在制模前和制模中予各组小鼠皮下注射不同浓度的重组人HGF(rhHGF),部分小鼠同时皮下注射抗rhHGF单抗。根据血清淀粉酶、脂肪酶水平、胰腺组织学炎症评分和胰腺超微结构的变化评估炎症程度,并测定胰腺匀浆中花生四烯酸代谢产物血栓素(TX)B2和6鄄酮(keto)鄄前列腺素(PG)F1α的水平。结果:与单纯炎症组相比,给予4μg/kg或20μg/kgrhHGF小鼠的血清淀粉酶、脂肪酶水平和胰腺组织学炎症评分显著降低,胰腺匀浆中TXB2水平显著降低,6鄄keto鄄PGF1α水平显著增高,但4μg/kg与20μg/kgrhHGF的疗效无显著差异。给予rhHGF的同时给予抗rhHGF单抗,小鼠的上述各项参数与单纯炎症组无显著差异。结论:外源性HGF能减轻雨蛙肽诱导的小鼠轻症急性胰腺炎,其机制可能与对花生四烯酸代谢的影响有关。抗HGF单抗能抵消HGF的生物学作用。
It is clinically important to treat mild acute pancreatitis efficiently in order to prevent probable progression to severe acute pancreatitis. Recently, hepatocyte growth factor (HGF) has drawn attention on whether it may attenuate acute pancreatitis in the rodents. Aims: To observe whether exogenous HGF can alter the severity of mild acute pancreatitis in mice, and to investigate its mechanism. Methods: Mild acute pancreatitis was induced by intraperitoneal injection of cerulein in mice. Different doses of recombinant human HGF (rhHGF) were given subcutaneously before and during the induction of the disease, respectively, some mice received subcutaneous injection of anti-rhHGF monoclonal antibody simultaneously. The grade of inflammation was evaluated according to the serum levels of amylase and lipase, the histological score of inflammation and the ultrastructural changes of pancreas. The levels of arachidonic acid metabolites thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1α in pancreas were also measured. Results: The serum levels of amylase and lipase, the histological score of inflammation, and the pancreatic TXB2 level were significantly reduced, whereas the pancreatic 6-keto-PGF1α level was markedly increased when 4 μg/kg or 20 μg/kg rhHGF were administered in comparison with those mice given cerulein only. However, there was no difference between the efficacy of 4 μg/kg and 20 μg/kg rhHGF. The parameters mentioned above in the mice given rhHGF plus anti-rhHGF monoclonal antibody showed no difference as compared with those mice given cerulein only. Conclusions: Exogenous HGF can attenuate cerulein-induced mild acute pancreatitis in mice. Its mechanism may be related to its effects on arachidonic acid metabolism. Anti-HGF monoclonal antibody can preclude the biological effects of HGF.
出处
《胃肠病学》
2004年第2期73-76,共4页
Chinese Journal of Gastroenterology
基金
上海市科委重点项目基金(No.02DJ14039)资助
关键词
肝细胞生长因子
小鼠
急性胰腺炎
花生四烯酸
炎症
血清胰酶
Hepatocyte Growth Factor
Acute Pancreatitis
Arachidonic Acid
Cerulein
Antibodies, Monoclonal
