Zhang Yue-Lu, Wang Ruo-Bing, Li Wei-Yi, Xia Fang-Zhou, Liu Lin
Department of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Department of Ophthalmology, Shandong University Qilu Hospital (Qingdao), Qingdao 266035, Shandong Province, China.
Int J Ophthalmol. 2017 Dec 18;10(12):1812-1818. doi: 10.18240/ijo.2017.12.04. eCollection 2017.
To explore the role of Pioglitazone (Pio) on a mouse model of retinal ischemia/reperfusion (I/R) injury and to elucidate the potential mechanism.
Retinal ischemia was induced in mice by increasing the intraocular pressure, and Pio was administered 4h though periocular injection before I/R. The number of cells in the ganglion cell layer (GCL) was counted 7d after retinal I/R injury. Glial fibrillary acidic protein (GFAP), nuclear factor-kappa B (NF-κB), p38, phosphorylated-p38, PPAR-γ, interleukin-1β (IL-1β), Toll-like receptor 4 (TLR4), NLRP3, cleaved caspase-1, caspase-1 were determined by real-time polymerase chain reaction and Western blotting.
Pio promoted the survival of retinal cells in GCL following retinal I/R injury (<0.05). Besides, retinal I/R injury stimulated the expression of GFAP and TLR4, which were partially reversed by Pio treatment (<0.05). Retinal I/R injury-upregulated expression of NLRP3, cleaved caspase-1, IL-1β was attenuated after Pio treatment (<0.05). Moreover, I/R injury induced activation of NF-κB and p38 were inhibited by Pio treatment (<0.05).
Pio promotes retinal ganglion cells survival by suppressing I/R-induced activation of TLR4/NLRP3 inflammasomes inhibiting NF-κB and p38 phosphorylation.
探讨吡格列酮（Pio）在小鼠视网膜缺血/再灌注（I/R）损伤模型中的作用，并阐明其潜在机制。
通过升高眼压诱导小鼠视网膜缺血，并在I/R前4小时通过眼周注射给予Pio。视网膜I/R损伤7天后，计数神经节细胞层（GCL）中的细胞数量。通过实时聚合酶链反应和蛋白质印迹法测定胶质纤维酸性蛋白（GFAP）、核因子-κB（NF-κB）、p38、磷酸化-p38、PPAR-γ、白细胞介素-1β（IL-1β）、Toll样受体4（TLR4）、NLRP3、裂解的半胱天冬酶-1、半胱天冬酶-1。
Pio促进视网膜I/R损伤后GCL中视网膜细胞的存活（<0.05）。此外，视网膜I/R损伤刺激了GFAP和TLR4的表达，Pio治疗可部分逆转这种表达（<0.05）。Pio治疗后，视网膜I/R损伤上调的NLRP3、裂解的半胱天冬酶-1、IL-1β的表达减弱（<0.05）。此外，Pio治疗可抑制I/R损伤诱导的NF-κB和p38的激活（<0.05）。
Pio通过抑制I/R诱导的TLR4/NLRP3炎性小体激活、抑制NF-κB和p38磷酸化来促进视网膜神经节细胞存活。
