TXNIP在高糖诱导的小鼠视网膜Müller细胞自噬中的作用及相关机制

目的:探讨硫氧还蛋白相互作用蛋白(thioredoxin interacting protein,TXNIP)对高糖诱导的小鼠视网膜Müller细胞自噬的影响及其可能机制。方法:采用高糖诱导体外培养的小鼠视网膜Muller细胞,通过RNA干扰降低TXNIP的表达,免疫荧光、Western blot和Real-time PCR检测自噬相关蛋白及丝氨酸/苏氨酸激酶/雷帕霉素靶蛋白(serine/threonine kinase 1/mechanistic target of rapamycin kinase,AKT/m TOR)的表达。结果:高糖诱导的Muller细胞中TXNIP、微管相关蛋白1轻链3α(microtubule associated protein 1 light chain 3 alpha,LC3Ⅱ)、Sequestosome1(p62/SQSTMl)的表达均显著增加(P<0.05);而TXNIP敲降的Muller细胞中自噬相关特征性蛋白(LC3Ⅱ、P62)的表达则显著降低(P<0.05)。结论:TXNIP可能通过AKT/m TOR信号通路来抑制糖尿病性视网膜病变中Müller细胞自噬活性,并引起细胞发生凋亡。

Role of TXNIP on Autophagy in Mouse Retinal Müller Glia under Hyperglycemia Conditions and Its Mechanisms

Objective: To investigate the molecular mechanism of autophagy of Muller cells induced by thioredoxin interacting protein(TXNIP) during DR development. Methods: Muller cells were high-glucose cultured and knockdown TXNIP using RNAi, then investigated the autophagy associated proteins and AKT/m TOR signaling pathway using immunofluorescence, Western blot and realtime PCR. Results: TXNIP and autophagy associated proteins such as LC3 II and p62 were observed to be highly expressed in Muller cells within high glucose culture. While LC3 II and p62 were declining upon TXNIP knockdown. Conclusion: TXNIP may inhibition Muller cells autophagy and apoptosis via AKT/m TOR pathway in the early stage of DR.