發(fā)布時間：2018-05-18 18:32

  本文選題：Resolvin + D1　； 參考：《重慶醫(yī)科大學》2017年碩士論文

【摘要】：目的:觀察Resolvin D1對STZ誘導的糖尿病大鼠視網膜中炎癥小體和NF-κB通路表達的影響,探討Resolvin D1對早期糖尿病視網膜病變的保護作用及相關機制。方法:鏈脲佐菌素(STZ,60mg/kg)腹腔注射誘導大鼠糖尿病模型,造模成功后飼養(yǎng)3個月。SD大鼠隨機分為對照組、STZ組、Resolvin D1(1000ng/kg)給藥組及賦形劑對照組。Evans-Blue評價大鼠血視網膜屏障通透性改變情況。HE染色觀察視網膜結構形態(tài)變化。利用Real-time PCR檢測大鼠視網膜NLRP3、ASC及caspase-1 m RNA表達水平。免疫組化觀察炎癥小體在視網膜分布及表達情況。Western blot檢測NLRP3,ASC,caspase-1 p20,IκBα,磷酸化NF-κB蛋白表達水平。酶聯免疫吸附試驗檢測炎性因子IL-1β及IL-18的分泌水平。結果:STZ組大鼠血視網膜通透性是正常對照組的2.4倍;STZ組及賦形劑對照組大鼠3個月視網膜結構疏松,細胞排列紊亂,而給予Resolvin D1干預后視網膜組織結構有了明顯改善;與正常對照組相比,STZ組及賦形劑對照組大鼠視網膜中炎癥小體及其下游炎性因子表達在基因及蛋白水平均明顯增加(P0.05),Resolvin D1干預后其表達水平降低(P0.05);與正常對照組相比,STZ組及賦形劑對照組大鼠視網膜NF-κB磷酸化水平明顯升高(P0.05),IκBα蛋白降解增多(P0.05),Resolvin D1干預后NF-κB磷酸化水平降低(P0.05),IκBα降解程度降低(P0.05)。結論:NLRP3炎癥小體通路及NF-κB通路在糖尿病視網膜病變發(fā)生發(fā)展中起重要作用,其表達在STZ誘導的糖尿病視網膜中顯著增高。Resolvin D1可能通過抑制炎癥小體激活以及抑制IκBα降解,減少NF-κB磷酸化水平抑制NF-κB通路的激活,從而抑制相關炎性因子釋放,對糖尿病視網膜病變起保護作用,為糖尿病視網膜病變治療提供新的研究思路。
[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 偽 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 偽 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 偽. 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.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R587.2;R774.1

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本文編號：1906734