抵抗素在伴高脂血症性急性坏死性胰腺炎大鼠发病中的作用

The Effect of Resistin in the Pathogenesis of Acute Necrotic Pancreatitis Rats Complicated with Hyperlipemia

目的探讨抵抗素在伴高脂血症性急性坏死性胰腺炎(ANP)发病机制中的可能作用。方法将50只雄性SD大鼠分为正常对照组(C组)5只,单纯ANP组(ANP组)15只、高脂对照组(H组)15只及高脂ANP组(HAP组)15只,分组采用高脂饲料喂养4周建立大鼠高脂血症模型,应用逆行胰胆管3.5%牛磺胆酸钠注射构建ANP大鼠模型,分别于造模后4,9,24h各处死5只大鼠。ELISA法测定各组不同时段血清抵抗素和TNF-α水平,临床全自动生化仪检测血脂及血清淀粉酶(Amyl),免疫组织化学方法观察胰腺组织中抵抗素及NF-κB p65表达,光镜下观察胰腺组织病理改变。结果 HAP组较ANP组胰腺炎病理损伤加重(病理评分P<0.05)。造模后各时间点,HAP组较ANP组血清TNF-α水平(P<0.05)和抵抗素水平(P<0.01)更高,胰腺组织NF-κB p65表达水平(P<0.05)和抵抗素表达水平(P<0.05)更高。血清TNF-α和抵抗素水平呈正相关(r=0.698,P<0.05);胰腺组织NF-κB p65表达和抵抗素表达呈正相关(r=0.839,P<0.01)。结论在ANP发病中,抵抗素可能通过促进转录因子NF-κB p65的表达及TNF-α的释放发挥生物学效应;HAP胰腺组织病理损害较重可能与抵抗素表达的增加相关。

Objective To explore the possible effect of resistin in the pathogenesis of HAP. Methods 50 healthy male SD rats were randomly divided into four groups （normal control group n= 5, ANP group n=15, hyperlipemia （H） control group n=15 and H with ANP group n=15）. H rat model was established by fed with high-fat diet（which consist of 87.8% normal diet, 10% lard, 2% cholesterol and 0.2% sodium cholate） for 4 weeks, and ANP rat model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct. Rats were sacrificed at 4, 9,24 h later respectively. Blood and pancreas tissues were gained. The level of serum resistin and TNF-α was determined with ELISA. Serum triglyceride （TG） and diastase （Amyl） was measured by fully automatic clinical biochemical analyzer. The expression of resistin and NF-κB p65 in pancreatic tissue was observed by the immuno- histochemical staining. Pancreatic histopathology was observed by light microscopy. Results Pathological injuries were more severe in HAP group than in ANP group （ P〈0. 05 ）. Each time point after ANP model was building, serum TNF-α level （P 〈 0.05） and serum resistin level （P 〈0. 01 ） were more higher in HAP group than in ANP group. The expression of NF-κB p65（P〈0.05 ） and the expression of resistin （P〈0.05）in the pancreas tissue in HL-HAP group were significant higher than in ANP group. Positive correlation was found between serum TNF-α and resistin Ievel（r=0. 698, P〈0.05）. Positive correlation was also found between the expression of NF-κB p65 and resistin in the pancreas tissue （r=0. 839, P〈0.01）. Conclusion Resistin may be involved in the pathogenesis of ANP, and the biological effect is correlated with promoting the expression of transcription factors NF-κB p65 and the release of TNF-α. The increase of resistin expression may be associated with the more serious pathological damage of pancreatic tissue in HAP.