TLR3和TLR4在特发性IgA肾病患儿肾组织及外周血单个核细胞中的表达

发布时间：2018-04-30 18:23

  本文选题：Toll样受体3 + Toll样受体4　； 参考：《新乡医学院》2017年硕士论文

【摘要】：背景特发性IgA肾病(IgA nephropathy,IgAN),是儿童常见的原发性肾小球肾炎,是一种以肾小球系膜区IgA沉积为主的临床病理综合征,常表现为急性上呼吸道或消化道感染后出现发作性肉眼血尿。早期研究学者认为此病是良性疾病,临床呈慢性进展,预后良好,但目前众多的资料显示约20%-40%的患者在确诊后的20年内进展到终末期肾脏病(ESRD),需要肾替代治疗,对儿童的生活质量及生命造成了严重威胁,故有必要对IgAN采取干预治疗,然而目前由于IgAN发病机理尚未完全清楚,IgAN的治疗方案有限,因此有必要探究IgAN的发病机制。研究表明,IgAN处理来自常见致病菌的共同外源性抗原失调,可引起异常的免疫反应、异常IgA的合成及肾损害,但具体通过何种途径导致免疫失衡仍不清楚。Toll样受体(Toll-like receptors,TLRs)是一种新型的、保守的模式识别受体,可表达于内皮细胞、免疫细胞和肾脏固有细胞等,识别病原体相关分子模式和损伤相关分子模式等,通过髓样分化因子-88(myeloid differentiation factor 88,MyD88)依赖信号传导通路和MyD88非依赖信号传导通路,激活核转录因子(nuclear factor,NF)-κB,引起细胞因子、趋化因子等表达增加,同时启动天然免疫和适应性免疫应答与炎症反应,成为感染性或非感染性肾脏病研究的热点。我们前期研究了TLR4和TLR7在儿童原发性肾病综合征患儿肾组织中的表达变化,证实了TLR4和TLR7参与儿童原发性肾病综合征的发病。那么TLRs是否参与IgAN的发病过程?IgAN是否存在TLRs的异常变化?目的探讨TLR3和TLR4在儿童特发性IgAN外周血单个核细胞及肾组织中的表达,为儿童IgAN的发病机制提供实验依据,同时为IgAN的治疗提供新靶点。方法收集2014年09月至2016年06月于我院儿科就诊且经肾穿刺活检,最后确诊的IgAN患者34例为IgAN组,同期在我院小儿外科行肾脏切除的肾肿瘤患儿7例为对照A组;以10例门诊健康体检儿童为对照B组。采用免疫组织化学法检测IgAN组与对照A组肾组织中TLR3和TLR4的表达情况;同时采用流式细胞术检测TLR3和TLR4在IgAN组与对照B组外周血单个核细胞中的阳性表达率。对TLR3和TLR4在IgAN组与对照组的阳性表达情况进行分析,研究IgAN患者中TLR3和TLR4的表达情况。结果1.外周血单个核细胞中TLR3和TLR4的表达:TLR3在对照B组外周血单个核细胞中几乎没有表达,而在IgAN组则呈现出明显的高表达,TLR4在对照B组外周血单个核细胞中有少量的表达,而在IgAN组的表达明显升高。IgAN组外周血单个核细胞中TLR3和TLR4的阳性表达率分别为(17.62±8.33)%和(23.85±11.82)%,均明显高于对照B组中TLR3(0.31±0.06)%和TLR4(3.02±0.09)%的表达,差异有统计学意义(P0.05)。2.肾组织TLR3和TLR4表达:TLR3、TLR4在肾组织的表达分别为胞核表达和胞浆表达。对照A组:肾小管上皮细胞有少量的TLR3表达,而肾小球中几乎无TLR3表达,TLR4在肾小管及肾小球中均无明显表达。IgAN组:TLR3和TLR4在肾小管上皮细胞均呈高表达,而肾小球系膜细胞有不同程度TLR3和TLR4表达。IgAN组肾组织中TLR3和TLR4的表达分别为(68.28±6.37)%和(0.048±0.018),均明显高于对照A组肾组织中TLR3(9.69±11.02)%和TLR4(0.003±0.001)的表达,差异有统计学意义(P0.01)。结论1.TLR3和TLR4在IgAN肾组织及外周血单个核细胞中表达均增加,提示TLR3和TLR4异常活化可能参与了IgAN的发病过程。2.根据TLR3和TLR4两种受体的主要识别配体类型,推断病毒及细菌感染可能通过免疫作用引起IgAN的肾损害。
[Abstract]:Background idiopathic IgA nephropathy (IgA nephropathy, IgAN) is a common primary glomerulonephritis in children. It is a clinicopathological syndrome mainly in mesangial mesangial region IgA deposition, often manifested by acute upper respiratory tract or digestive tract infection with paroxysmal hematuria. The prognosis is good, but at present, many data show that about 20%-40% patients have progressed to end-stage renal disease (ESRD) within 20 years after diagnosis, which requires renal replacement therapy, which poses a serious threat to the quality of life and life of children. Therefore, it is necessary to take intervention treatment to IgAN, however, the pathogenesis of IgAN is not completely clear, Ig The treatment scheme of AN is limited, so it is necessary to explore the pathogenesis of IgAN. The study shows that IgAN treatment of common exogenous antigen disorders from common pathogenic bacteria can cause abnormal immune response, abnormal IgA synthesis and renal damage, but the specific way of immune imbalance is still unclear on the.Toll receptor (Toll-like receptors, TLRs). It is a new, conservative pattern recognition receptor that can be expressed in endothelial cells, immune cells and renal cells, identification of pathogen associated molecular patterns and damage related molecular patterns, and through the myeloid differentiation factor -88 (myeloid differentiation factor 88, MyD88) dependent signal transduction pathway and MyD88 non dependent signal transduction pathway. Nuclear factor (NF) - kappa B activates the expression of cytokines, chemokines and other expressions. It also activates natural and adaptive immune responses and inflammatory responses. It has become a hot spot in the study of infectious or non infectious renal diseases. We studied TLR4 and TLR7 in the renal tissue of children with primary nephrotic syndrome. The expression changes have confirmed the involvement of TLR4 and TLR7 in the pathogenesis of primary nephrotic syndrome in children. Then does TLRs participate in the pathogenesis of IgAN? Is there an abnormal change in TLRs in IgAN? Objective to explore the expression of TLR3 and TLR4 in the peripheral blood mononuclear cells and renal tissues of children with idiopathic IgAN, and to provide an experimental basis for the pathogenesis of IgAN in children. At the same time, it provides new targets for the treatment of IgAN. Methods from 2014 09 months to 06 months in 2016, the pediatric patients in our hospital were treated with renal biopsy, 34 of the final confirmed IgAN patients were group IgAN. In the same period, 7 cases of renal tumor children with nephrectomy in our hospital were compared with the control group, and 10 cases of healthy physical examination children were compared with the B group. The expression of TLR3 and TLR4 in the renal tissue of group IgAN and control group A was detected by immunohistochemical method, and the positive expression rate of TLR3 and TLR4 in the peripheral blood mononuclear cells of group IgAN and control B group was detected by flow cytometry. The positive expression of TLR3 and TLR4 in the IgAN group and the control group was analyzed. Results the expression of TLR3 and TLR4 in 1. peripheral blood mononuclear cells: TLR3 was almost not expressed in the peripheral blood mononuclear cells of the control group B, but in the IgAN group, the expression of TLR4 was obviously expressed in the peripheral blood mononuclear cells of the control group of B group, and the expression of the peripheral blood mononuclear significantly increased in the group of IgAN. The positive expression rates of TLR3 and TLR4 in the cells were (17.62 + 8.33)% and (23.85 + 11.82)%, respectively, which were significantly higher than those of the control group B TLR3 (0.31 + 0.06)% and TLR4 (3.02 + 0.09)%. The difference was statistically significant (P0.05).2. renal tissue TLR3 and TLR4 expression: TLR3, TLR4 in the renal tissue expression and cytoplasm expression respectively. There was a small amount of TLR3 expression in the epithelial cells of the tubule, and there was almost no TLR3 expression in the glomeruli. There was no significant expression of TLR4 in the renal tubules and glomeruli. TLR3 and TLR4 were highly expressed in the renal tubular epithelial cells, while the expression of TLR3 and TLR4 in the glomerular mesangial cells expressed TLR3 and TLR4 in the.IgAN group of.IgAN group (68.28 + 6, respectively). .37)% and (0.048 + 0.018) were significantly higher than the expression of TLR3 (9.69 + 11.02)% and TLR4 (0.003 + 0.001) in the renal tissue of the control group A, and the difference was statistically significant (P0.01). Conclusion 1.TLR3 and TLR4 were increased in IgAN renal tissue and peripheral blood mononuclear cells, suggesting that the abnormal activation of TLR3 and TLR4 may be involved in IgAN pathogenesis. The main recognition ligand types of the two receptors of TLR4 and IgAN infer that the virus and bacterial infection may cause renal damage by immunization.

【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R726.9

【参考文献】

相关期刊论文 前10条

1 李青;郑敏;张露;刘利华;孙伟;;TLR4、TBK/IRF3信号通路介导肾小管上皮细胞与单核细胞相互作用[J];中国中西医结合肾病杂志;2015年11期

2 王缨;汪国平;李弼民;;IgA肾病大鼠肾组织中Toll样受体4的表达及意义[J];广东医学;2015年20期

3 王缨;汪国平;李弼民;;活性维生素D3对IgA肾病大鼠肾组织中Toll样受体4表达的影响[J];中国现代医学杂志;2015年25期

4 王云;徐达良;董扬;;Toll样受体与IgA肾病发病机制的研究进展[J];国际儿科学杂志;2014年06期

5 孙婧;孔祥雷;陈萍;崔美玉;许冬梅;;Toll样受体在原发性肾小球疾病发病机制中的作用[J];国际泌尿系统杂志;2014年05期

6 林洪升;杨海波;谢恺庆;杨利;周静文;周马林;黄企光;;TLR2和TLR4在牛型结核分枝杆菌诱导的肾小管上皮细胞损伤中的作用[J];中国病理生理杂志;2014年06期

7 张芳敏;韩子明;赵德安;;Toll样受体4和Toll样受体7在儿童原发性肾病综合征患儿肾组织中的表达及意义[J];临床儿科杂志;2014年06期

8 吴小川;廖娟;;IgA血管炎和IgA肾病是同一种疾病吗?[J];中华实用儿科临床杂志;2014年09期

9 王瑜;吕柳青;张莉;杨柳;陈钦开;吕金雷;;TLR4在糖尿病肾病大鼠肾组织中的表达[J];南昌大学学报(医学版);2013年12期

10 张玉军;刘淑霞;杨敏;;狼疮性肾炎小鼠肾组织中HMGB1、TLR4、STAT3、PCNA的表达及意义[J];山东医药;2013年08期

相关硕士学位论文 前3条

1 熊梅梅;高糖环境下人肾小管上皮细胞天然免疫信号TLR4与血管紧张素Ⅱ的对话关系及其病理生理改变[D];南昌大学医学院;2015年

2 周才芳;TLR4及其调控因子SOCS3在IgA肾病发病机制中作用的初步探讨[D];南昌大学;2014年

3 张芳敏;TLR4和TLR7在儿童原发性肾病综合征患儿肾组织中的表达变化及临床意义[D];新乡医学院;2014年

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