罗格利酮对伴高脂血症大鼠重症急性胰腺炎肺损伤的作用研究  

Effects of rosiglitazone on hyperlipidemic rats with severe acute pancreatitis secondary to lung injury

作　　者：赵凯亮[1] 陈辰[1] 余佳[1] 陈晓燕[1] 赵亮[1] 胡鹏[1] 王卫星[1] 

机构地区：[1]武汉大学人民医院肝胆腔镜外科,武汉430060

出　　处：《中华急诊医学杂志》2016年第11期1418-1423,共6页Chinese Journal of Emergency Medicine

基　　金：国家自然科学基金（81370562）;中央高校基本科研业务费专项资金资助青年教师资助项目（2042015kf0086）

摘　　要：目的探讨罗格列酮（ROSI）对伴高脂血症大鼠重症急性胰腺炎（SAP）肺损伤的保护作用及其可能机制。方法雄性SD大鼠120只，脂肪乳剂灌胃两周。随机（随机数字法）分为6组：高脂血症组（HL）、伴高脂血症SAP组（HP）、罗格列酮干预组（HRP）、罗格列酮拮抗组（HRGP）、罗格列酮对照组（HR）、拮抗剂对照组（HG），每组各20只。HP组、HRP组及HRGP组逆行胰胆管注射5％牛磺胆酸钠（1mL／kg）建立SAP模型。HL组、HR组和HG组操作同HP组、HRP组及HRGP组，但胰胆管内仅注入等容量生理盐水；HRP组和HR组于造模前经股静脉注射ROSI（10mg／kg）；HRGP组于注射ROSI前30min经股静脉注射GW9662（0．3mg／kg），其余操作同HRP组，HG组仅于造模前30min经股静脉注射GW9662（0．3mg／kg）。于12h观察大鼠胰腺、肺脏病理学变化；计算肺湿干比（W／D）；测定血清淀粉酶（AMY）、甘油三酯（TG）、总胆固醇（TC）的含量；免疫组织化学法检测各组肺组织NF-κB065蛋白的表达；Western-Blot法检测各组肺组织肿瘤坏死因子（TNF-α）及细胞间黏附分子（ICAM-1）的蛋白表达水平。结果HL组和HP组的TG、TC的血清水平均明显高于HR组和HRP组（1．24±0．28，1．14±0．08伽．0．41±0．17，0．58±0．12；14．86±1．47，12．42±0．96掷．6．52±2．04，7．36±0．95；均P〈0．05）；HP组、HRGP组大鼠血清AMY、肺湿干比（W／D）、胰腺、肺组织病理学评分、肺组织NF-KB065蛋白表达及TNF．0l、ICAM．1蛋白表达水平均较HL组、HR组及HG组的各项指标有显著升高（6501．9±3770．0，5922．2±925．9 vs ．1139．3±35．6，1070．8±67．0，1012．4±94．7；3．14±0．16，3．06±0．12掷．1．81±0．13，1．76±0．23，1．83±0．18；均P〈0．05）；HRP组的大鼠肺脏病理学评分、肺湿干比（W／D）、肺组织NF．KB065蛋白表达及TNF-α、ICAM-1蛋白表达水平均较HP组�Objective To explore the effects of rosiglitazone （ROSI）, a peroxisome proliferator- activated receptors-gamma （PPAR-γ） ligand, on hyperlipidemia in rats with severe acute pancreatitis （SAP） associated with lung injury. Methods A total of 120 male SD rats received intragastric administration of high fat diet for two weeks to induce experimental hyperlipemia. The hyperlipidemic rats were randomly （ random number） divided into six groups ： hyperlipidemia （HL） group （ n = 20 ）, hyperlipidemia with SAP （HP） group （ n = 20 ）, hyperlipidemia with rosiglitazone intervention （HRP） group （n = 20）, hyperlipidemia with rosiglitazone and antagonist to rosiglitazone （HRGP） group （n = 20 ）, rosiglitazone control （HR） group （ n = 20） and antagonist control （HG） group （ n = 20）. The SAP was induced by a retrograde infusion of 5% sodium tauroholate into bile-pancreatic duct, and the SAP was established in HP group, HRP group and HRGP group. In HL group, HR group and HG group, equivalent volume of normal saline was used instead of sodium taurocholate. In HRP group and HR group, ROSI （6 mg/kg） was administered via the femoral vein 1 hour prior to the administration of sodium taurocholate. In HRGP group, GW9662 （0. 3 mg/kg）, an antagonist to PPRA-gamma, was given via the femoral vein 30 min prior to the administration of ROSI. In HG group, only GW9662 （0. 3 mg/kg） was given via the left femoral vein 30 min prior to pretend SAP modeling. Rats from each group were sacrificed by exsanguination 12 h after SAP modeling. Blood samples were taken from all subjects to measure serum amylase （AMY）, total cholesterol （TC）, triglycerides （TG）, Successive sections of the paraffin embedded tissue from pancreas and lung were taken for pathological examination with hematoxylin-eosin （HE） staining. Histopathological changes of pancreatic and pulmonary tissues observed under light microscope were evaluated. In pulmonary tissue, nuclear factor-kappa B （NF-

关 键 词：罗格列酮 重症急性胰腺炎 高脂血症 肺损伤 核因子-ΚB 

分 类 号：R589.2[医药卫生—内分泌] R576[医药卫生—内科学]