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PPARγ在外源性保护素D1减轻小鼠内毒素性急性肺损伤中的作用 被引量:3

Role of PPARγ in exogenous protectin D1-induced reduction of endotoxin-induced acute lung injury in mice
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摘要 目的 评价过氧化物酶体增殖物激活受体(PPARγ)在外源性保护素D1(PD1)减轻小鼠内毒素性急性肺损伤中的作用.方法 清洁级健康雄性BABL∕C小鼠32只,体重20~25 g,6~8周龄,采用随机数字表法分为4组(n=8):假手术组(S组)小鼠经口气管插管滴入生理盐水,1 h后尾静脉注射生理盐水;急性肺损伤组(ALI组)小鼠经口气管插管滴入脂多糖(LPS)3 mg∕kg,1 h后尾静脉注射生理盐水;PD1组小鼠经口气管插管滴入 LPS 3 mg∕kg, 1 h 后尾静脉注射 PD1 200 ng;PPARγ拮抗剂组(GW9662组)小鼠经口气管插管滴入 LPS 3 mg∕kg,1 h后尾静脉注射 GW9662 1 mg∕kg及PD1 200 ng.于气管给予LPS后24 h时处死小鼠,以PBS行左侧支气管肺泡灌洗,肺泡灌洗液(BALF)行中性粒细胞计数,ELISA法测定IL-1β、TNF-α及IL-6浓度;取右肺组织行HE染色,光镜下观察,行肺损伤评分,Western blot法检测PPARγ的表达.结果 与S组比较,ALI组小鼠BALF中性粒细胞计数、IL-1β、TNF-α、IL-6浓度和肺损伤评分升高,肺组织PPARγ表达下调( P<0. 01);与ALI组比较,PD1组小鼠BALF中性粒细胞计数、IL-1β、TNF-α、IL-6浓度和肺损伤评分降低,肺组织PPARγ表达上调(P<0. 01);与PD1组比较,GW9662组小鼠BALF中性粒细胞计数、IL-1β、TNF-α、IL-6浓度和肺损伤评分升高,肺组织PPARγ表达下调(P<0. 01).结论 PPARγ激活参与了外源性PD1减轻小鼠内毒素性急性肺损伤的过程. Objective To evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) in exogenous protectin D1 ( PD1)-induced reduction of endotoxin-induced acute lung injury (ALI) in mice. Methods Thirty-two clean-grade healthy male BABL∕C mice, weighing 20-25 g, aged 6-8 weeks, were divided into 4 groups (n=8 each) using a random number table method: sham operation group (group S), ALI group, PD1 group and PPARγ antagonist GW9662 group. Mice underwent oral tra-cheal intubation, normal saline was instilled, and 1 h later normal saline was injected via the tail vein in group S. Mice underwent oral tracheal intubation, lipopolysaccharide (LPS) 3 mg∕kg was instilled, and 1 h later normal saline was injected via the tail vein in group ALI. Mice underwent oral tracheal intubation, LPS 3 mg∕kg was instilled, and 1 h later PD1 200 ng was injected via the tail vein in group PD1. Mice un-derwent oral tracheal intubation, LPS 3 mg∕kg was instilled, and 1 h later GW9662 1 mg∕kg and PD1 200 ng were injected via the tail vein in group GW9662. Mice were sacrificed at 24 h after intratracheal instilla-tion of LPS, the left lung was lavaged with phosphate buffer solution, and the broncho-alveolar lavage fluid (BALF) was collected for determination of neutrophil count and concentrations of interleukin-1beta ( IL-1β), tumor necrosis factor-alpha ( TNF-α) and IL-6 ( by enzyme-linked immunosorbent assay). Right lung tissues were obtained and cut into sections which were stained with haematoxylin and eosin and exam-ined with a light microscope for microscopic examination of the pathological changes which were scored (lung injury score) and for determination of the expression of PPARγ in lung tissues. Results Compared with group S, the neutrophil counts in BALF, concentrations of IL-1β, TNF-α and IL-6 and lung injury score were significantly increased, and the expression of PPARγ was down-regulated in group ALI ( P<0. 01). Compared with group ALI, the neutrophil counts in BALF, concentrations of IL-1β, TNF-α
作者 孔繁丽 罗婷 吴裕超 孙志鹏 Kong Fanli;Luo Ting;Wu Yuchao;Sun Zhipeng(Department of Anesthesiology,Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital),Tongji Medical College,Huazhong University of Science &Technology,Wuhan430016,China)
出处 《中华麻醉学杂志》 CAS CSCD 北大核心 2018年第7期878-881,共4页 Chinese Journal of Anesthesiology
基金 湖北省知识创新专项(自然科学基金)(2018CFC856)。
关键词 过氧化物酶体增殖物激活受体 抗原 CD95 保护素D1 呼吸窘迫综合征 成人 Peroxisome proliferator-activated receptors Antigens,CD59 Respiratory distress syndrome,adult
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