脂蛋白脂酶基因缺陷的极度高甘油三酯血症小鼠胰腺炎的研

目的:利用一种特殊的脂蛋白脂酶（LPL）基因缺陷的极度高甘油三酯血症(HTG)小鼠，作为HTG性胰腺炎的实验动物模型，研究其胰腺炎发病特点。 方法:检测野生型及LPL缺陷的遗传性极度HTG小鼠血浆淀粉酶活性并观察胰腺的形态学改变，研究自发性胰腺炎的发生情况；通过腹腔注射左旋精氨酸（L-Arg）诱导小鼠发生急性胰腺炎（AP），研究HTG时胰腺炎易感性的变化。 结果:对胰腺组织的病理观察表明，LPL缺陷小鼠中约34.5%可发生自发性胰腺炎，特点主要为炎细胞浸润和腺泡破坏，有时伴纤维化和出血，病变严重程度与血浆TG水平呈正相关（r=0.604,P<0.05），血浆淀粉酶活性与对照组相比无明显差异。L-Arg诱导的LPL缺陷实验组小鼠胰腺炎病理损害明显重于野生型实验组（P<0.01），但两组间血浆淀粉酶活性无显著差异。 结论:LPL缺陷的HTG小鼠可发生自发性胰腺炎，对于L-Arg诱导的AP比野生型小鼠更加易感，为进一步研究HTG性胰腺炎的发病机制提供了理想的动物模型。

Hereditary extremely hypertriglyceridemic mice are more susceptible to acute pancreatitis

AIM: To investigate the susceptibility to pancreatitis in LPL deficient hypertriglyceridemic (HTG) mice and to establish an experimental animal model for study on HTG pancreatitis. METHODS: LPL deficient HTG mice was rescued by somatic gene transfer. Plasma amylase and pathological changes in pancreas were analyzed for comparison between LPL deficient HTG and wild type mice to assess the incidence of spontaneous pancreatitis. In addition, acute pancreatitis(AP) was induced by L-arginine for further assessment. RESULTS: According to pancreatic pathological scores, incidence of spontaneous pancreatitis was 34.5% in LPL deficient mice. The affected LPL deficient HTG mice showed typical morphological changes of pancreatitis with inflammatory infiltration and acinar necrosis, accompanying fibrosis or hemorrhage occasionally, while there was no pancreatitis in wild type mice. The severity of pathological changes correlated positively with plasma TG levels (r=0.604,P<0.05). However, the amylase levels did not increase significantly. When AP inducer, L-arginine, was injected at low dose (2 g/kg body weight, ip), LPL deficient mice showed more severe pathological damage than wild type mice (P<0.01), though there was no significant change in amylase levels. CONCLUSION: LPL deficient HTG mice developed spontaneous pancreatitis, and the susceptibility to L-arginine-induced pancreatitis increased. These findings show that HTG results in pancreatitis on mice as on human. Therefore, LPL deficient HTG mice would be a useful experimental model for study of HTG pancreatitis.