国际麻醉学与复苏杂志   2013, Issue (3): 6-6
    
罗格列酮对盲肠结扎穿孔脓毒症大鼠肺损伤的影响
张蕊, 鲍红光, 斯妍娜, 徐丽, 沈妍1()
1.南京医科大学附属南京医院(南京市第一医院)麻醉科
Effects of rosiglitazone on pulmonary injury of septic rats induced by cecal ligation puncture
 全文:
摘要:

目的 观察PPARɣ激动剂罗格列酮对盲肠结扎穿孔(CLP)所致脓毒症大鼠肺损伤的影响。方法 80只健康雄性Wistar大鼠,采用随机数字表法分为5组:假手术组(SHAM组);盲肠结扎穿孔组(CLP组);罗格列酮组(ROSI组),CLP前30分钟静脉注射罗格列酮0.3mg/Kg;PPARɣ拮抗剂GW9662组(GW组):CLP前30分钟静脉注射GW9662 0.3mg/Kg; GW9662+罗格列酮组(GW+ROSI组):依次于CLP前30分钟静脉注射GW9662 0.3mg/Kg、CLP前15分钟静脉注射罗格列酮0.3mg/Kg。于CLP后6小时、24小时各组随机抽取8只大鼠处死并留取血液及肺组织。测定各组肺组织湿/干质量比(W/D);肺组织髓过氧化物酶(MPO)活性;酶联免疫吸附法(ELISA)测定血浆肿瘤坏死因子-α(TNF-α)水平;实时荧光定量聚合酶链反应(real-time PCR)测定肺组织高迁移率族蛋白B1(HMGB1)mRNA水平。结果 与SHAM组比较,CLP组、ROSI组、GW组、GW+ROSI组大鼠W/D比、MPO活性、TNF-α水平以及HMGB1mRNA水平在CLP后6、24小时增加(P<0.05);与CLP组、GW组、GW+ROSI组分别比较,ROSI组大鼠W/D比、MPO活性、TNF-α水平以及HMGB1mRNA水平在CLP后6、24小时降低(P<0.05)。结论 罗格列酮可以降低CLP脓毒症大鼠TNF-α水平以及HMGB1mRNA水平,减轻肺水肿程度及炎症损伤程度,对肺损伤具有保护作用。

关键词: 脓毒症;肺损伤;罗格列酮
Abstract:

Objective To observe the effects of rosiglitazone, an agonist of peroxisome proliferator-activated receptor ɣ (PPARɣ), on pulmonary injury in septic rats induced by cecal ligation puncture. Methods Eighty healthy male Wistar rats were randomly divided into 5 groups: sham group(group SHAM); cecal ligation puncture group(group CLP); rosiglitazone group(group ROSI): rats were intravenous injected with rosiglitazone 0.3mg/Kg 30 minutes before CLP; GW9662 group(group GW): rats were intravenous injected with GW9662 0.3mg/Kg 30 minutes before CLP; GW9662 plus rosiglitazone group(group GW+ROSI): rats were injected intravenously with GW9662 0.3mg/Kg 30 minutes before CLP and then with rosiglitazone 0.3mg/Kg 15 minutes before CLP. Eight rats were sacrificed at 6 and 24 h after CLP respectively in each group. Blood was reserved for the measurement of the level of plasma TNF-α by ELISA and lung tissues were removed for the detections of lung wet/dry ratio, lung myeloperoxidase(MPO) activity, and lung tissue HMGB1mRNA expression by real-time PCR. Results Compared with group SHAM, the lung W/D ratio, MPO activity, plasma TNF-α level and the lung tissue HMGB1mRNA expression were significantly increased in group CLP, group ROSI, group GW and group GW+ROSI(P<0.05). Compared with group CLP, group GW and group GW+ROSI respectively, the lung W/D ratio, MPO activity, plasma TNF-α level and the lung tissue HMGB1mRNA expression were significantly decreased in group ROSI(P<0.05). Conclusion Rosiglitazone can decrease the plasma TNF-α level and the lung tissue HMGB1mRNA expressionα level and attenuate the pulmonary edema and inflammation in septic rats by CLP. It can have protective function on pulmonary injury.

Key words: Sepsis; Pulmonary injury; Rosiglitazone