高脂血症促使大鼠急性胰腺炎胰腺腺泡由凋亡趋向坏死

摘要

目的 通过建立高脂血症性急性胰腺炎大鼠模型,探讨高脂血症可能加重急性胰腺炎病程的机制.方法 D-果糖饮食诱导SD大鼠的产生高脂血症,在此基础上通过腹腔注射蛙皮素诱导急性胰腺炎,并且设立正常组、高脂血症组和急性胰腺炎组作为对照.8周后,取大鼠血浆检测血糖、血脂和游离脂肪酸等指标;收集大鼠胰腺以及胰周组织,检测组织匀浆中ADP与ATP比值,通过Western blot法检测组织中caspase-3和caspase-8等蛋白以及其底物的表达情况,对组织切片进行HE染色并通过TUNEL法分析组织凋亡和坏死的情况.结果 高脂血症性急性胰腺炎大鼠的血浆中血脂、游离脂肪酸等指标偏高;caspase-3和caspase-8活性片断表达下调,而其底物蛋白降解较少;TUNEL分析阳性率偏低,以上提示胰腺组织凋亡蛋白活性受到一定的抑制;另外,ADP与ATP比值相对较高,提示胰腺组织更易产生坏死反应.结论 笔者推测高脂血症可能通过促进大鼠胰腺组织由凋亡趋向坏死,从而加重急性胰腺炎病变程度.%Objective To establish the model of hyperlipidemie acute pancreatitis(AP)to explore the mechanism of hyperlipidemia in aggravating AP.Methods Sprague-Dawley rats were divided into four groups at radmon:1)control group(C);2)hyperlipidemic group(TG);3)acute pancreatitis group(AP);4)hyperlipidemic acute pancreatitis group(HAP).After 8 weeks,blood,pancreas and peripancreas tissue were collected from each rats for determination of various parameters.Results The levels of hyperilidemic index were elevated in HAP group compared with those of other groups.The ADP/ATP ratio was obviously increased in HAP group.Caspase-3 and caspase-8 of HAP group presented in zymogen forms,while in AP group they were in activity forms.After the pancreas issue were stained bv HE and further analyzed through TUNEL assay,we found that there were more pancreatic acinar cells undergoing necrosis in HAP group.Conclusion Hyperilidemia may promote the course of apoptosis to necrosis of pancreatic acinar cells,which may be the mechanism of deterioration in hyperlipidemic acute pancreatitis.