Liu Lili, Chen Junyi, Zhang Xiaofang, Cui Xue, Qiao Nana, Zhang Yun, Yang Jie
Department of Pediatrics, Qilu Hospital of Shandong University, No. 107, West Wenhua Road, Jinan City 250012, Shandong Province, China.
Department of Pathology, Shandong University of Medicine, No. 44, West Wenhua Road, Jinan City 250012, Shandong Province, China.
Biosci Rep. 2020 May 29;40(5). doi: 10.1042/BSR20192639.
The present study aims to reveal the molecular mechanism of peroxisome proliferator-activated receptor γ (PPARγ) on sepsis-induced acute lung injury (ALI). To do that, the rat injury model was established using cecal ligation and perforation (CLP) method, followed by different treatments, and the rats were divided into Sham group, CLP group, CLP + rosiglitazone (PPARγ agonist) group, CLP + GW9662 (PPARγ inhibitor) group, CLP + bpV (phosphatase and tensin homolog (PTEN) inhibitor) group, CLP + GW9662 + bpV group. Compared with Sham group, the mRNA and protein expression levels of PPARγ were down-regulated, the inflammation levels were elevated, and the apoptosis was increased in CLP group. After treatment with rosiglitazone, the protein expression level of PPARγ was significantly up-regulated, the phosphorylation level of PTEN/β-catenin pathway was decreased, the PTEN/β-catenin pathway was inhibited, the lung injury, inflammation and apoptosis were reduced. The opposite effect was observed after treatment with GW9662. Besides, bpV inhibited PTEN/β-catenin pathway, and relieved the lung tissue injury. The overexpression of PPARγ reduced inflammatory response and inhibited apoptosis in sepsis-induced ALI. Furthermore, PPARγ relieved the sepsis-induced ALI by inhibiting the PTEN/β-catenin pathway.
本研究旨在揭示过氧化物酶体增殖物激活受体γ（PPARγ）在脓毒症诱导的急性肺损伤（ALI）中的分子机制。为此，采用盲肠结扎穿孔（CLP）法建立大鼠损伤模型，随后进行不同处理，并将大鼠分为假手术组、CLP组、CLP + 罗格列酮（PPARγ激动剂）组、CLP + GW9662（PPARγ抑制剂）组、CLP + bpV（磷酸酶和张力蛋白同源物（PTEN）抑制剂）组、CLP + GW9662 + bpV组。与假手术组相比，CLP组PPARγ的mRNA和蛋白表达水平下调，炎症水平升高，细胞凋亡增加。罗格列酮处理后，PPARγ蛋白表达水平显著上调，PTEN/β-连环蛋白通路磷酸化水平降低，PTEN/β-连环蛋白通路被抑制，肺损伤、炎症和细胞凋亡减少。GW9662处理后观察到相反的效果。此外，bpV抑制PTEN/β-连环蛋白通路，减轻肺组织损伤。PPARγ的过表达减轻了脓毒症诱导的ALI中的炎症反应并抑制了细胞凋亡。此外，PPARγ通过抑制PTEN/β-连环蛋白通路减轻脓毒症诱导的ALI。
