AD小鼠模型VDRAs对TLR2、TLR4及CRAMP的调控作用研究

发布时间：2018-03-11 00:11

本文选题：特应性皮炎　切入点：VDRAs　出处：《天津医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的观察在特应性皮炎(AD)小鼠模型中维生素D受体激动剂(VDRAs)的干预对皮损以及Toll受体2、Toll受体4(TLR2、TLR4)和鼠阳离子抗菌肽CRAMP的影响,并探讨其相互关联机制。方法把25只雌性BALB/c小鼠随机划分为5组,其分别为空白组、AD模型组、AD模型不干预组、PBS对照组、VDRAs治疗组,每组分别为5只。除空白组以外的其余4组,均用二硝基氯苯(DNCB)诱导小鼠特应性皮炎模型。AD造模成功后,模型组小鼠直接处死,AD模型不干预组造模完成后不予以任何处理,VDRAs治疗组小鼠腹腔注射VDRAs液,PBS对照组小鼠腹腔注射PBS液,两组均为每3日注射1次,总计5次。实验干预完成后,对各组小鼠背部皮损的改变情况进行观察,随后处死小鼠取背部皮肤组织做组织病理切片和免疫组化,用显微镜观察各组小鼠背部皮损处的组织改变情况,免疫组化染色后观察各组小鼠TLR2、TLR4及C RAMP在皮损中的表达水平和表达定位,Real Time PCR检测各组小鼠皮损中TLR2、TLR4及CRAMP的RNA含量并定量分析其变化。结果 VDRAs治疗组小鼠皮损较AD模型不干预组和PBS对照组明显改善,免疫组化和Real-Time PCR结果示VDRAs治疗组小鼠皮损中CRAMP的表达高于AD模型不干预组和PBS对照组,TLR2和TLR4的表达较PBS对照组和AD模型组低,其差异有统计学意义(P0.01)。结论在AD小鼠模型中,VDRAs可抑制TLR2、TLR4表达,上调鼠阳离子抗菌肽CRAMP的表达。
[Abstract]:Objective To observe the effect on atopic dermatitis (AD) in a mouse model of vitamin D receptor agonist (VDRAs) intervention on lesions and Toll 2 receptor, Toll receptor 4 (TLR2, TLR4) and the effect of rat cationic antimicrobial peptide CRAMP, and to explore the correlation mechanism. Methods 25 female BALB/c mice were randomly divided into the 5 groups were control group, AD model group, AD model group, PBS control group, VDRAs treatment group, each group was 5. In addition to the blank group of the other 4 groups, with two nitrochlorobenzene (DNCB) induced by atopic dermatitis model.AD after successful modeling, model groups of mice were executed, the AD model is not the intervention group after modeling without any treatment, VDRAs treatment group were injected with VDRAs solution, the PBS control group were injected with PBS solution, two groups were injected 1 times every 3 days, a total of 5 times. After the completion of the experimental intervention, the changes of mice back skin the Observe, then the mice were killed to take back the skin tissue for pathology and immunohistochemistry, microscope observed mice back skin lesions tissue changes were observed after TLR2 immunohistochemical stain, expression level in the lesions and the localization of TLR4 and C RAMP, TLR2 Real Time PCR lesions were detected in the analysis of TLR4 and CRAMP, change of RNA content and quantitative. Results VDRAs mice treated with AD model lesions of non intervention group and PBS control group improved significantly, the expression of immunohistochemistry and Real-Time PCR results showed that VDRAs treatment of CRAMP mice in the lesions was higher than that of AD model group and PBS control group, the expression of TLR2 and TLR4 compared with PBS control group and AD model group, the difference was statistically significant (P0.01). Conclusion in a mouse model of AD, VDRAs can inhibit the expression of TLR4, TLR2, expression of rat cationic antimicrobial peptide CRAMP.

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R758.2;R-332

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