间充质干细胞对兔自身免疫性干眼模型病理改变及细胞因子表达的影响

发布时间：2018-03-25 02:28

本文选题：间充质干细胞　切入点：兔自身免疫性干眼　出处：《眼科新进展》2017年08期

【摘要】：目的建立兔自身免疫性干眼模型,观察间充质干细胞(mesenchymal stem cells,MSCs)治疗后兔自身免疫性干眼的组织病理学变化及泪腺组织中细胞因子表达的变化。方法取健康成年雌性新西兰白兔24只24眼,采用随机数学表法将兔分为正常对照组、干眼模型组和MSCs治疗组,每组各8只8眼。MSCs治疗6周后,观察兔眼组织病理学改变,实时荧光定量PCR检测泪腺组织中Th1、Th17细胞分化相关细胞因子mRNA相对表达量。流式细胞仪检测干眼模型组和MSCs治疗组兔泪腺组织和脾脏组织中调节性T细胞(CD4+Foxp3+细胞)占淋巴细胞的比例。结果 MSCs治疗6周后,取各组兔泪腺并行HE染色显示:正常对照组未见或仅见少量淋巴细胞浸润;干眼模型组泪腺内部分腺体细胞出现萎缩,腺管周围和小血管周围可见散在分布的淋巴细胞汇集区;与干眼模型组相比,MSCs治疗组泪腺内淋巴细胞浸润减轻,腺泡细胞形态较好。与干眼模型组比较,MSCs治疗组结膜组织中淋巴细胞浸润聚集显著减轻,上皮结构完整,变性和萎缩细胞较少见。MSCs治疗组泪腺组织中Th1特征性细胞因子IFN-γ以及转录因子T-bet mRNA表达水平较干眼模型组明显下降,差异均有统计学意义(均为P0.05);Th17细胞分化相关细胞因子IL-17表达水平有下降趋势,但两组差异无统计学意义(P0.05);其转录因子RORrt mRNA的表达水平较干眼模型组显著降低,差异有统计学意义(P0.05)。MSCs治疗组泪腺组织中炎症因子TNF-α表达较干眼模型组显著降低,而抑炎因子TGF-β的表达较干眼模型组显著升高,差异均有统计学意义(均为P0.05)。泪腺组织中干眼模型组调节性T细胞(CD4+Foxp3+细胞)占淋巴细胞的比例为10.0%,而MSCs治疗组中调节性T细胞占淋巴细胞的比例为27.8%,MSCs治疗组调节性T细胞较干眼模型组显著升高,差异有统计学意义(P0.05)。结论 MSCs可以减轻自身免疫性干眼的组织病理学改变,对自身免疫性干眼具有一定的免疫调节及治疗作用,其免疫调控作用可能与调节抑炎因子和促炎因子平衡有关。
[Abstract]:Objective to establish an autoimmune dry eye model in rabbits. The histopathological changes of autoimmune dry eyes and the expression of cytokines in lacrimal gland were observed after mesenchymal stem cells were treated with mesenchymal stem cells (MSCs). Methods 24 eyes of 24 healthy adult female New Zealand white rabbits were selected. The rabbits were randomly divided into normal control group, dry eye model group and MSCs treatment group. Eight eyes of 8 eyes in each group were treated for 6 weeks. The histopathological changes of rabbit eyes were observed. Real-time fluorescence quantitative PCR was used to detect the relative expression of Th1T17 cell differentiation related cytokine mRNA in lacrimal gland tissue. Flow cytometry was used to detect regulatory T cell CD4 Foxp3 cells in lacrimal gland and spleen of rabbits in dry eye model group and MSCs treatment group. Results after 6 weeks of MSCs treatment, The lacrimal gland of each group was stained with HE staining: no or only a small amount of lymphocyte infiltration was observed in the normal control group, and some gland cells in the dry eye model group were atrophied and scattered around the ducts and small vessels of the lacrimal gland. Compared with the dry eye model group, the lymphocyte infiltration and acinar cell morphology in the lacrimal gland of the MSCs treatment group were less than those in the dry eye model group, and the lymphocyte infiltration and aggregation in the conjunctival tissue in the MSCs treatment group were significantly reduced compared with the dry eye model group, and the epithelial structure was intact. The expression level of Th1 characteristic cytokine IFN- 纬 and transcription factor T-bet mRNA in lacrimal gland tissue of MSCs treatment group was significantly lower than that in dry eye model group. The difference was statistically significant (all the levels of IL-17 expression of differentiation related cytokines of P0.05T17 cells decreased, but there was no significant difference between the two groups, and the expression level of transcription factor RORrt mRNA was significantly lower than that of dry eye model group. The expression of inflammatory factor TNF- 伪 in lacrimal gland of the treated group was significantly lower than that in the dry eye group, while the expression of TGF- 尾 in the dry eye model group was significantly higher than that in the dry eye model group. The percentage of regulatory T cell CD4 Foxp3 cells in the dry eye model group was 10.0, while that in the MSCs treatment group was 27.8m. Compared with the dry eye model group, the ganglionic T cells increased significantly. Conclusion MSCs can attenuate the histopathological changes of autoimmune dry eyes and has some immunomodulatory and therapeutic effects on autoimmune dry eyes. Its immune regulation may be related to regulating the balance of anti-inflammatory factors and pro-inflammatory factors.
【作者单位】：天津北辰医院眼科;天津医科大学眼科医院眼视光学院;
【基金】：国家自然科学基金资助(编号:81100646) 天津市科委自然科学基金资助(编号:11JCYBJC26000,13JCYBJC23300) 教育部留学回国人员科研启动基金资助项目(编号:第48批) 天津市北辰区科技发展计划项目(编号:BC2014-10)~~
【分类号】：R-332;R777.34

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