AIM: To investigate the protective effect of human umbilical cord mesenchymal stem cells (hUCMSCs) modified by the LIF gene on the retinal function of diabetic model rats and preliminarily explore the possible mechanism. METHODS: A stably transfected cell line of hUCMSCs overexpressing leukemia inhibitory factor (LIF) was constructed. Overexpression was verified by fluorescent quantitative polymerase chain reaction (qPCR). Forty-eight adult Sprague-Dawley rats were randomly divided into a normal control group (group A), streptozotocin-induced diabetic control group (group B), diabetic rats at 3mo injected with empty vector-transfected hUCMSCs (group C) or injected with LIF-hUCMSCs (group D). Four weeks after the intravitreal injection, analyses in all groups included retinal function using flash electroretinogram (F-ERG), retinal blood vessel examination of retinal flat mounts perfused with fluorescein isothiocyanate-dextran (FITC-dextran), and retinal structure examination of sections using hematoxylin and eosin staining. Expression levels of adiponectin (APN), high-sensitivity C-reactive protein (hs-CRP), and neurotrophin-4 (NT-4) in each group was detected using immunohistochemistry, PCR, Western blotting, and ELISA, respectively. RESULTS: A stable transgenic cell line of LIF-hUCMSCs was constructed. F-ERG and FITC-dextran examinations revealed no abnormalities of retinal structure and function in group A, severe damage of the retinal blood vessels and function in group B, and improved retinal structure and function in group C and especially group D. qPCR, ELISA, and Western blot analyses revealed progressively higher APN and NT-4 expression levels in groups B, C, and D than in group A. hs-CRP expression was significantly higher in group B than in groups A, C, and D, and was significantly higher in group C than in group D (P<0.05). CONCLUSION: LIF-hUCMSCs protect the retina of diabetic rats by upregulating APN and NT-4 expression and downregulating hs-CRP expression in the retina.

中文翻译：

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LIF-huMSCs对糖尿病模型大鼠视网膜的保护作用

目的：探讨LIF基因修饰的人脐带间充质干细胞（hUCMSCs）对糖尿病模型大鼠视网膜功能的保护作用，并初步探讨其可能机制。方法：构建稳定转染的过表达白血病抑制因子（LIF）的hUCMSCs细胞系。通过荧光定量聚合酶链反应（qPCR）验证过表达。48只成年Sprague-Dawley大鼠随机分为正常对照组（A组）、链脲佐菌素诱导糖尿病对照组（B组）、3mo注射空载体转染hUCMSCs的糖尿病大鼠（C组）或注射LIF-hUCMSC（D 组）。玻璃体内注射后 4 周，所有组的分析包括使用闪光视网膜电图 (F-ERG) 进行的视网膜功能、使用异硫氰酸荧光素-葡聚糖 (FITC-葡聚糖) 灌注的视网膜平片的视网膜血管检查以及使用苏木精和伊红染色。分别采用免疫组化、PCR、Western blotting、ELISA检测各组脂联素（APN）、高敏C反应蛋白（hs-CRP）、神经营养蛋白-4（NT-4）的表达水平。结果：构建了稳定的转基因LIF-hUCMSCs细胞系。F-ERG和FITC-葡聚糖检查显示A组视网膜结构和功能未见异常，B组视网膜血管和功能严重损伤，C组尤其是D组视网膜结构和功能改善。qPCR、ELISA ，Western blot分析显示B、C、D组APN、NT-4表达水平逐渐高于A组。B组hs-CRP表达显着高于A、C、D组，并且C组显着高于D组(P<0.05)。结论:LIF-hUCMSCs通过上调视网膜APN和NT-4表达、下调hs-CRP表达来保护糖尿病大鼠视网膜。