高脂血症性胰腺炎大鼠瘦素、瘦素受体表达的动态变化

Dynamic changes of leptin and leptin receptor expression in hyperlipidemic acute pancreatitis in rats

目的:探讨瘦素及瘦素受体在大鼠高脂血症性胰腺炎(HLAP)中的动态变化。方法:将60只SD雄性大鼠随机分为3组:正常对照组(NC组),高脂血症组(HL组),高脂血症性胰腺炎组(HLAP组)。采用高脂饲料喂养3周后经腹腔注射L-精氨酸500 mg/100 g体重制作大鼠高脂血症性胰腺炎模型。各组分别于造模后24 h、36 h处死半数大鼠,观察血清淀粉酶、瘦素水平、细胞因子IL-1β、TNF-α和IL-10的变化。并对胰腺的病理学评分、胰腺组织瘦素、瘦素受体的表达和定位评分。结果:HL组血清IL-1β、TNF-α、瘦素水平较NC组高(P<0.01);而IL-10水平、病理学评分以及胰腺组织瘦素和瘦素受体表达与NC组无差异。造模后24 h,HLAP组血淀粉酶和IL-1β、TNF-α、瘦素水平均较HL组及NC组升高(P<0.01),而IL-10与HL组相当;HLAP组的胰腺瘦素、瘦素受体表达较HL组及NC组增加(P<0.01),胰腺组织损害也明显增强(P<0.01)。造模后36 h,HLAP组血淀粉酶和瘦素水平下降。HLAP组IL-1β、TNF-α及IL-10水平继续上升,胰腺病理损害进一步加重(P<0.01)。此外,HLAP组瘦素及瘦素受体表达也均下降(P<0.01)。结论:正常胰腺中有瘦素及其受体的存在。在HLAP时作为保护性机制,内源性的瘦素表达能够明显增加;但这种内源性瘦素的增加出现早,维持时间短,不足以抑制强烈的炎症反应。

Objective To observe the dynamic changes of leptin and the leptin receptor in hyperlipidemic acute pancreatitis（HLAP）in rats.Methods Sixty SD male rats were randomly divided into 3 groups with 20 rats in each one：（1） normal control（NC） group;（2） hyperlipidemia（HL） group;（3） hyperlipidemic acute pancreatitis（HLAP） group.The HLAP model was made by a single intraperitoneal injection of 500 mg/100 g body weight of L-arginine after feeding with high-fat diet for three weeks.Half of animals in each group were killed 24 and 36 hours after the injection.Blood samples were taken for the examination of serum amylase,leptin,interleukin（IL）-1β,tumor necrosis factor（TNF）-α,IL-10,while pancreatic tissues were taken for leptin and leptin receptor expression and localization,and pathological evaluation.Results In the HL group,the serum level of IL-1β,TNF-α and leptin was higher than that of the NC group（P0.01）,while the level of IL-10 and pathological score showed no difference between them.At the first 24 hours in HLAP group,the level of amylase,IL-1β,TNF-α and leptin was higher than that of the NC group（P0.01）,but the level of IL-10 was the same as in NC group.The leptin and leptin receptor expression in HLAP groups were higher,as compared to those in the HL and NC groups（P0.01）.After 36 hours,the level of amylase and leptin in the HLAP group went down,but the level of IL-1β,TNF-α and IL-10 continued to increase and the pancreatic damage aggravated.The leptin and leptin receptor expression decreased in the HLAP group（P0.01）.Conclusions There are leptin and its receptor expression in the normal pancreas tissue.As a protective mechanism,endogenous leptin expression can be significantly increased in HLAP.But the increase of endogenous leptin is not only early but also transitory,and it could not inhibit the strong inflammatory response.