罗格列酮对脓毒症大鼠空肠短肽载体的调控机制研究

Regulation mechanism of rosiglitazone on the oligopeptide transporter (PepT1) in septic rats after cecal ligation and puncture

目的探讨罗格列酮对脓毒症大鼠空肠短肽载体(PepT1)表达的调控作用及其机制。方法健康成年SD大鼠48只,随机分为盲肠结扎穿刺(CLP)组(C组)、假手术组(S组)、罗格列酮组(R组)、罗格列酮+胰岛素组(RI组)、CLP+胰岛素组(CI组)和正常对照组(N组),每组8只。C、CI、S组大鼠术前30min给予等量生理盐水灌胃;R、RI组CLP前30min给予罗格列酮(20mg/kg)灌胃;RI、CI组在CLP后150min经股静脉注射胰岛素(10U/kg);N组大鼠未做任何处理。6组大鼠分别于术前30min及术后30、60、90、120、150min测空腹血糖,并在150min时取动脉血和近端空肠待检。采用紫外分光光度法测定血清D-乳酸水平,ELISA法检测血清IL-6、TNF-α、IL-10水平变化,Western blotting检测空肠PepT1表达。结果术前给予罗格列酮可降低脓毒症大鼠呼吸频率、外周血中性粒细胞水平及CLP术后血糖,降低血清炎性因子TNF-α、IL-6、IL-10水平以及D-乳酸水平,增加基础状态下和胰岛素刺激下的PepT1表达。结论罗格列酮可通过降低炎性因子水平而提高脓毒症时空肠肠黏膜PepT1的表达。

Objective To explore the regulation effect and its mechanism of rosiglitazone on the oligopeptide transporter（PepT1） expression in rats after cecal ligation and puncture（CLP）.Methods Forty-eight SD rats were randomly divided into 6 groups（8 each）： CLP group（C group）,sham operation group（S group）,CLP＋rosiglitazone group（R group）,CLP＋rosiglitazone＋insulin group（RI group）,CLP＋insulin group（CI group）,and normal control group（N group）.Rats in C,S and CI groups received 0.9% NaCl solution by intragastric administration 30min before CLP or sham operation,while in R and RI group,rats received rosiglitazone instead.Rats in RI and CI group received insulin through femoral vein 150min after CLP.Glucose was measured at 30min preoperatively and every 30min postoperatively（30,60,90,120,150min）.Arterial blood and proximal jejunum were harvested at 150min.Plasma D-lactate was determined by ultraviolet spectrophotometry.Serum IL-6,TNF-α and IL-10 were determined by ELISA.Pept1 expression was detected by Western blotting.Results When rosiglitazone was given preoperatively,the respiratory rate,neutrophil count,glucose concentration,and the levels of TNF-α,IL-6,IL-10 and plasma D-lactate all decreased significantly after CLP（P＆lt;0.05 or P＆lt;0.01）.Rosiglitazone-pretreatment increased PepT1 expression in both baseline and insulininduced conditions（P＆lt;0.05）.Conclusion Rosiglitazone may increase the PepT1 expression in jejunal mucosa by reducing inflammatory cytokines in sepsis.