肝细胞生长因子治疗重型急性胰腺炎的实验研究

Study of Hepatocyte Growth Factor on the Treatment of Severe Acute Pancreatitis

目的探讨肝细胞生长因子(HGF)有效治疗实验性重型急性胰腺炎(SAP)的可能性。方法72只雄性SD大鼠随机分为假手术组、对照组、治疗组和单抗组。对照组、治疗组和单抗组均灌注5%牛黄胆酸钠复制SAP模型;治疗组制模后即分别给予1、2、10μg/kg的重组人HGF(rhHGF)静脉注射,3h后重复1次;单抗组在制模并给予2μg/kg体重rhHGF的同时皮下注射0.8mg/kg的抗rhHGF单抗。各组分别于制模后3、6h取大鼠腹水、血、胰腺及肺脏组织,评价炎症程度。另取30只雄性SD大鼠随机分为对照组和治疗组,制模及制模后早期3h处理同前,制模3h后2μg/kg体重rhHGF每8h皮下注射给药,72h后比较两组大鼠存活率。结果给予2、10μg/kg体重rhHGF的治疗组大鼠,制模后3、6h血浆淀粉酶、脂肪酶水平和胰腺组织学炎症评分均低于对照组,制模后6h急性肺损伤较轻。制模72h后治疗组大鼠存活率为73.3%,对照组存活率为26.7%(P<0.01)。结论HGF治疗大鼠SAP,可以减轻炎症反应,提高早期预后。

ObjectiveTo investigate if exogenous hepatocyte growth factor(HGF) could treat severe acute pan-(creatitis)(SAP) in rats.MethodsSeventy-two male SD rats were randomly divided into 4 groups,i.e., sham operation, control, HGF and HGF plus antibody. SAP in the control, HGF and HGF plus antibody groups was induced by retrograde infusion of 5% sodium taurocholate into the biliopancreatic ducts. Rats of the sham operation group were infused with physical saline instead. After the induction of pancreatitis, the rats of the HGF group were given 1, 2 or 10 μg/kg of rhHGF via venous injections while rats of the HGF plus antibody group were given 0.8 mg/kg of the (anti)-rhHGF monoclonal antibody subcutaneoously as well as 2 μg/kg of rhHGF. Three or six hours after biliopan-(creatic) infusion, the blood, samples were collected pancreas and lungs of the rats were harvested. Plasma amylase and lipase were determined, pancreatic histological scoring for pancreatitis was graded, and damages of the lungs were assessed independently by two pathologists. Another thirty male rats were divided into groups of control and HGF. They were treated as above during the early 3 h after induction of inflammation, except that 2 μg/kg was the only dosage of rhHGF, then 2 μg/kg of rhHGF(the HGF group only) was subcutaneously given every 8 h until 72 h after induction of inflammation. The survival ratio of rats from both groups were compared.ResultsThe HGF group rats receiving 2, 10 μg/kg of rhHGF showed lower levels of plasma amylase and lipase, lower histological scores, and lighter lung damages. The survival rate of the HGF group was 73.3%, and the control group was 26.7%(P<0.01).Conclusion(Admi-nistration) of enough exogenous HGF after induction of SAP could attenuate inflammation in rats, and thus improve early prognosis.