PPAR-γ在大鼠重症急性胰腺炎伴高脂血症中的表达及意义

Expression of peroxisome proliferater-activated receptor gamma in rats with severe acute pancreatitis associate with hyperlipemia and its significance

目的观察高脂血症对大鼠重症急性胰腺炎严重程度的影响及过氧化物酶增殖物激活受体γ(peroxisome proliferater activated receptor gamma,PPAR-γ)在重症急性胰腺炎和重症急性胰腺炎伴高脂血症中的表达差异,初步探讨高脂血症影响重症急性胰腺炎炎症程度的发病机制。方法40只雄性Sprague-Dawley大鼠,随机分为4组:正常对照组(C组)10只,重症急性胰腺炎组(SAP组)10只,高脂血症组(TG组)10只,重症急性胰腺炎伴高脂血症组(SAP-TG组)10只。C组和SAP组普通饲料喂养,TG组和SAP-TG组高脂饲料喂养。4周后C组及TG组腹主动脉采血行甘油三酯检查,取胰腺及肺脏组织匀浆,RT-PCR法测PPAR-γ的表达。SAP组及SAP-TG组禁食12h后制作重症急性胰腺炎模型,6h后腹主动脉采血进行丙二醛(malondialdehyde,MDA)检测;测腹水量;取胰腺部分组织及肺脏匀浆,RT-PCR测PPAR-γ的表达;取胰腺组织送病理检查,常规HE染色。胰腺病理组织评分采用Schmidt法。结果血脂变化:高脂饲料喂养4周后,TG组大鼠甘油三酯水平明显升高,达(1.68±0.21)mmol/L,明显高于正常对照组,有显著性差异(P<0.05)。胰腺及肺脏组织PPAR-γ表达:与C组相比,TG组及SAP组PPAR-γ表达均升高,有显著性差异(P<0.05);与SAP组相比,SAP-TG组PPAR-γ表达含量下降,有显著性差异(P<0.05)。MDA含量:与SAP组相比,SAP-TG组MDA含量明显升高,达(2.321±0.241)μmol/L,有显著性差异(P<0.05)。胰腺腹水量:与SAP组相比,SAP-TG组胰腺腹水量升高,分别为(11.624±2.009)%和(15.800±1.046)%,有显著性差异(P<0.05)。病理评分:与SAP组相比,SAP-TG组各项炎症病理评分明显升高,有显著性差异(P<0.05)。结论高脂血症可加重重症急性胰腺炎炎症程度,可抑制急性炎症反应时PPAR-γ的升高程度,可能是通过降低PPAR-γ表达加重重症急性胰腺炎炎症程度。

Objective To investigate the influence of hyperlipemia in severe acute pancreatitis SAP, the expressinn of peroxisome proliferater activated receptor gamma（PPAR-γ） and to discuss its significance in rats with SAP and SAP associate with hyperlipemia. Methods Forty male Sprague-Dawley rats were randomly divided into four groups： control group （ C group, n = 10）, acute pancreatitis group （ SAP group, n = 10）, hyperlipidemia group （TG group, n = 10）, acute pancreatitis associated with hyperlipidemia group （ SAP-TG group, n = 10）. SAP group and control group ： balance feed for 4 weeks ; TG group and SAP-TG group ： high fat feed for 4 weeks. Four weeks later, control group and TG group were sacrificed. Blood sample, pancreatic tissues and lung tissues were collected. AEROSET automatic biochemical analyzer was used to inspect triglyceride. The expression of PPAR-γ was inspected by RT-PCR. Rats were sacrificed at 6 hours after the onset of SAP model operation. Blood sample and pancreatic tissues were collected and the expresion of MDA in blood was examined by TBA method, measuring the amount of ascites. With part of pancreatic tissues, PPAR-γ expression was detected by RT-PCR. Pancreatic tissues were fixed with 10% neutral formalin and sent for histopathologic examination, and HE staining. Schmidt scoring method was used to evaluate pancreatic pathology. Results Lipid changes：after 4 weeks of high-fat diet, rats TG triglyceride levels were significantly increased, and the difference was significant（P 〈 0.05）. PPAR-γ expression in pancreas and lung tissues： compared with group C, expression of PPAR- gamma in group TG and group SAP were increased, the difference was significant （ P 〈 0.05 ）. Compared with group SAP, expression of PPAR-γ in group SAP-TG decreased, the difference was also significant （ P 〈 0.05 ）. MDA content ： compared with group SAP, MDA content in group SAP-TG was significantly higher, the difference was significant （P 〈 0.05 ）. Pancreatic ascites ： compared with group SAP, pancreatic ascites of group SAP-TG increased, the difference was significant （ P 〈 0.05 ）. Pancreatic pathology grade ： compared with group SAP, inflammatory pathology scores of group SAP-TG increased significantly, the difference was significant （ P 〈 0.05 ）. Conclusion Hyperlipemia can aggravate the inflammation of acute pancreatitis;Hyperlipemia can reduce the expression of PPAR-γ in acute inflammatory reac- tion. The decrease of PPAR-γ may be one of the reasons that hyperlipidemia add the inflammation of severe acute pan- creatitis.