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[摘要] 目的 探讨过氧化物酶体增殖物激活受体-γ激动剂对胰腺炎大鼠肺损伤的保护作用及调节机制。 方法 72只大鼠随机分为假手术组、模型组和罗格列酮组，各组再分为术后6 h、12 h、24 h组。模型组采用两次腹腔注射L-精氨酸制备SAP模型，罗格列酮组术后30 min静脉注射10%罗格列酮6 mg/kg，假手术组腹腔注射等体积生理盐水。观察大鼠肺病理改变，测定肺TLR4、NF-κB、肺髓过氧化物酶活性、肺干/湿重比、血清TNF-α、IL-1β、IL-6含量。使用重复测量方差分析，SNK-q检验比较差异。 结果 ROSI组大鼠肺组织病理损害较SAP组减轻；与SAP组比较，肺内NF-κB、TLR4蛋白下降（P<0.05），髓过氧化物酶活性及肺干/湿重比降低（P<0.05）；ROSI组外周血IL-1β、IL-6、TNF-α含量与SAP组比较明显下降（P<0.05）。 结论 PPAR-γ激动剂能减轻急性胰腺炎大鼠肺组织的损伤，抑制NF-κB、TLR4表达，降低促炎细胞因子水平，推测PPAR-γ激动剂对NF-κB/TLR4通路的调节可能是胰腺炎的保护机制之一。
[关键词] 急性胰腺炎；过氧化物酶体增殖物激活受体；核转录因子-κB；Toll样受体
[中图分类号] R576 [文献标识码] A [文章编号] 1673-9701（2017）18-0038-04
Protection of PPAR-γ agonists on lung injury in rats with acute pancreatitis
LU Bei1 YU Yuanquan2 YIN Junjie1 CAI Yang1
1.Department of HPB Surgery， Hangzhou First People’s Hospital， Hangzhou 310006， China； 2.Department of HPB Surgery， the Second Affiliated Hospital of Zhejiang University School of Medicine， Hangzhou 310009， China
[Abstract] Objective To find the protection of PPAR-γ agonists on injured lung cells in rats and mechanism during acute pancreatitis. Methods Rats were divided randomly into three groups： sham operation group， SAP model group， rosiglitazone group. Each group was divided into 6 h， 12 h， and 24 h group after operation. SAP rats model were made via twice peritoneal injection of L-arginine. Rats in ROSI group were injected with 6 mg/kg of 10% rosiglitazone via femoral vein 30 min after operation. Sham operation group rats were peritoneally injected of same volume NS as SAP group. Pathological changes of lung tissue， TLR4， NF-κB， MPO， dry and wet ratio in lung tissue were tested. Serum TNF-α， interieukin-1β， interieukin-6 were also determined. Results The pathological injuries of lung cell were relieved in ROSI group compared with SAP group. There were statistic differences in TLR4， NF-κB， MPO， dry and wet ratio in lung between ROSI and SAP group， which were decreased in ROSI group compared with SAP group（P<0.05）. TNF-α， IL-1β， IL-6 were decreased in ROSI group compared with those in SAP group（P<0.05）. Conclusion The lung tissue injury during SAP may relived by PPAR-γ agonists， and also decrease NF-kappa B， TLR4 and inflammatory cytokines. The probable reason is that PPAR-γ agonists protect pancreas by adjusting NF-κB/TLR4 signal pathway.
[Key words] Severe acute pancreatitis； Peroxisome proliferator activating receptor； Nuclear factor-kappa B； Toll-like receptor
由重癥急性胰腺炎引发的胰外损害中急性肺损伤较为常见，严重者可发生呼吸衰竭甚至死亡。胰腺连锁炎症反应与核转录因子-κB（nuclear transcription factor-κB，NF-κB）关系密切，其中过氧化物酶体增殖物激活受体-γ（peroxisome proliferators-activated receptor-γ，PPAR-γ）激动剂如罗格列酮可能与NF-κB活化抑制以及AP进展有关。本研究证明罗格列酮能减轻SAP大鼠肺损害，其机制可能与NF-κB/TLR4相关。 1 材料与方法
1.1实验材料
选择72只SD大鼠，体质量269.7～320.4 g（浙江省中医药大学实验动物中心提供）。戊巴比妥钠、L-精氨酸针（Sigma，USA），罗格列酮（Cayman，USA），NF-κB、TLR4抗体（Santa Cruz，USA）、MPO等ELISA试剂盒购自R
[关键词] 急性胰腺炎；过氧化物酶体增殖物激活受体；核转录因子-κB；Toll样受体
[中图分类号] R576 [文献标识码] A [文章编号] 1673-9701（2017）18-0038-04
Protection of PPAR-γ agonists on lung injury in rats with acute pancreatitis
LU Bei1 YU Yuanquan2 YIN Junjie1 CAI Yang1
1.Department of HPB Surgery， Hangzhou First People’s Hospital， Hangzhou 310006， China； 2.Department of HPB Surgery， the Second Affiliated Hospital of Zhejiang University School of Medicine， Hangzhou 310009， China
[Abstract] Objective To find the protection of PPAR-γ agonists on injured lung cells in rats and mechanism during acute pancreatitis. Methods Rats were divided randomly into three groups： sham operation group， SAP model group， rosiglitazone group. Each group was divided into 6 h， 12 h， and 24 h group after operation. SAP rats model were made via twice peritoneal injection of L-arginine. Rats in ROSI group were injected with 6 mg/kg of 10% rosiglitazone via femoral vein 30 min after operation. Sham operation group rats were peritoneally injected of same volume NS as SAP group. Pathological changes of lung tissue， TLR4， NF-κB， MPO， dry and wet ratio in lung tissue were tested. Serum TNF-α， interieukin-1β， interieukin-6 were also determined. Results The pathological injuries of lung cell were relieved in ROSI group compared with SAP group. There were statistic differences in TLR4， NF-κB， MPO， dry and wet ratio in lung between ROSI and SAP group， which were decreased in ROSI group compared with SAP group（P<0.05）. TNF-α， IL-1β， IL-6 were decreased in ROSI group compared with those in SAP group（P<0.05）. Conclusion The lung tissue injury during SAP may relived by PPAR-γ agonists， and also decrease NF-kappa B， TLR4 and inflammatory cytokines. The probable reason is that PPAR-γ agonists protect pancreas by adjusting NF-κB/TLR4 signal pathway.
[Key words] Severe acute pancreatitis； Peroxisome proliferator activating receptor； Nuclear factor-kappa B； Toll-like receptor
由重癥急性胰腺炎引发的胰外损害中急性肺损伤较为常见，严重者可发生呼吸衰竭甚至死亡。胰腺连锁炎症反应与核转录因子-κB（nuclear transcription factor-κB，NF-κB）关系密切，其中过氧化物酶体增殖物激活受体-γ（peroxisome proliferators-activated receptor-γ，PPAR-γ）激动剂如罗格列酮可能与NF-κB活化抑制以及AP进展有关。本研究证明罗格列酮能减轻SAP大鼠肺损害，其机制可能与NF-κB/TLR4相关。 1 材料与方法
1.1实验材料
选择72只SD大鼠，体质量269.7～320.4 g（浙江省中医药大学实验动物中心提供）。戊巴比妥钠、L-精氨酸针（Sigma，USA），罗格列酮（Cayman，USA），NF-κB、TLR4抗体（Santa Cruz，USA）、MPO等ELISA试剂盒购自R