ResolvinD1对糖尿病大鼠视网膜炎症小体及NF-κB通路影响

发布时间：2018-05-18 18:32

本文选题：Resolvin + D1　；参考：《重庆医科大学》2017年硕士论文

【摘要】：目的:观察Resolvin D1对STZ诱导的糖尿病大鼠视网膜中炎症小体和NF-κB通路表达的影响,探讨Resolvin D1对早期糖尿病视网膜病变的保护作用及相关机制。方法:链脲佐菌素(STZ,60mg/kg)腹腔注射诱导大鼠糖尿病模型,造模成功后饲养3个月。SD大鼠随机分为对照组、STZ组、Resolvin D1(1000ng/kg)给药组及赋形剂对照组。Evans-Blue评价大鼠血视网膜屏障通透性改变情况。HE染色观察视网膜结构形态变化。利用Real-time PCR检测大鼠视网膜NLRP3、ASC及caspase-1 m RNA表达水平。免疫组化观察炎症小体在视网膜分布及表达情况。Western blot检测NLRP3,ASC,caspase-1 p20,IκBα,磷酸化NF-κB蛋白表达水平。酶联免疫吸附试验检测炎性因子IL-1β及IL-18的分泌水平。结果:STZ组大鼠血视网膜通透性是正常对照组的2.4倍;STZ组及赋形剂对照组大鼠3个月视网膜结构疏松,细胞排列紊乱,而给予Resolvin D1干预后视网膜组织结构有了明显改善;与正常对照组相比,STZ组及赋形剂对照组大鼠视网膜中炎症小体及其下游炎性因子表达在基因及蛋白水平均明显增加(P0.05),Resolvin D1干预后其表达水平降低(P0.05);与正常对照组相比,STZ组及赋形剂对照组大鼠视网膜NF-κB磷酸化水平明显升高(P0.05),IκBα蛋白降解增多(P0.05),Resolvin D1干预后NF-κB磷酸化水平降低(P0.05),IκBα降解程度降低(P0.05)。结论:NLRP3炎症小体通路及NF-κB通路在糖尿病视网膜病变发生发展中起重要作用,其表达在STZ诱导的糖尿病视网膜中显著增高。Resolvin D1可能通过抑制炎症小体激活以及抑制IκBα降解,减少NF-κB磷酸化水平抑制NF-κB通路的激活,从而抑制相关炎性因子释放,对糖尿病视网膜病变起保护作用,为糖尿病视网膜病变治疗提供新的研究思路。
[Abstract]:Aim: to observe the effect of Resolvin D1 on the expression of inflammatory corpuscles and NF- 魏 B pathway in the retina of diabetic rats induced by STZ, and to explore the protective effect of Resolvin D1 on early diabetic retinopathy and its related mechanism. Methods: streptozotocin (STZ) 60 mg / kg was injected intraperitoneally to induce diabetic model in rats. Three months after successful modeling, SD rats were randomly divided into control group (STZ group) and excipient control group (Resolvin D _ (1 +) 1000 ng 路kg ~ (-1). The changes of blood retinal barrier permeability in rats were evaluated by using Evans-Blue. The changes of retinal structure and morphology were observed by HE staining. Real-time PCR was used to detect the expression of ASC and caspase-1 m RNA in rat retina. The distribution and expression of inflammatory corpuscles in the retina were observed by immunohistochemistry. Western blot was used to detect the expression of NLRP3ASCCaspase-1 p20 I 魏 B 伪 and phosphorylated NF- 魏 B protein. Enzyme linked immunosorbent assay (Elisa) was used to detect the secretion of IL-1 尾 and IL-18. Results the blood retinal permeability of the rats in the control group was 2.4-fold that in the control group and that in the excipient control group. The retinal structure was loose and the cells were disordered at 3 months. The retinal tissue structure was obviously improved after the intervention of Resolvin D1. Compared with the normal control group and the excipient control group, the expression of inflammatory corpuscles and its downstream inflammatory factors in the retina of the STZ group and the excipient control group were significantly increased at both the gene and protein levels, and the expression level of P0.05 / Resolvin D1 was significantly decreased after the intervention of Resolvin D1, which was similar to that in the normal control group. Compared with STZ group and excipient control group, the phosphorylation level of NF- 魏 B increased significantly in retina of rats. The degradation of I 魏 B 伪 protein increased after intervention of P0.05 and Resolvin D1, and the phosphorylation level of NF- 魏 B decreased. Conclusion the inflammatory corpuscle pathway and NF- 魏 B pathway play an important role in the pathogenesis and development of diabetic retinopathy, and their expression in the diabetic retinas induced by STZ is significantly increased. Resolvin D1 may inhibit the activation of inflammatory corpuscles and the degradation of I 魏 B 伪. Decreasing the phosphorylation level of NF- 魏 B inhibits the activation of NF- 魏 B pathway, which inhibits the release of related inflammatory factors and protects diabetic retinopathy and provides a new approach for the treatment of diabetic retinopathy.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2;R774.1

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