原发性肾病综合征中HMGB-1、NF-κB的相关性研究

发布时间：2018-05-12 21:11

本文选题：原发性肾病综合征 + 高迁移率族蛋白-1　；参考：《湖南师范大学》2014年硕士论文

【摘要】：研究背景：原发性肾病综合征(primary nephritic syndrome)是一种常见的免疫炎症性疾病,目前其发病机制尚不十分明确,大多数学者认为,发病过程中起主导作用的还是免疫介导和炎症损伤。多种炎症因子及免疫反应参与了肾病的发病机制,与疾病的进展有着直接关系。高迁移率族蛋白-1(high mobility group box-1,HMGB-1)是一种较新型的炎症细胞因子,其普遍存在于真核生物体内,可存在于细胞内及细胞外。目前国内外相关研究证实,HMGB-1在慢性肾功能不全、狼疮性肾炎、糖尿病肾病、急性肾功能损害、ANCA相关性血管炎肾损害、肾缺血再灌注损害等疾病中均呈高表达。在信号转导机制的研究中证实,HMGB-1可与其受体RAGE、Toll样受体(Toll-like receptor,TLR2/TLR4)等相互作用,通过活化MAPK. MyD88等多种途径最终活化NF-κB(nuclear factor-kappa B,NF-κB),引发炎症反应。既往已有研究证实NF-κB在肾病综合征患者中呈高水平表达,参与了原发性肾病综合征的发生与发展过程。目前国内外关于原发性肾病综合征与炎症因子HMGB-1的相关性研究及其在原发性肾病综合征患者血清中的变化尚未见报道,分析其与NF-KB的相关性,进一步探讨其在原发性肾病综合征发病中的作用。目的：通过对原发性肾病综合征患者外周血清中HMGB-1.NF-κB浓度的测定及两者间相互关系的分析,探讨HMGB-1在原发性肾病综合征中的作用。方法：收集我院2013年1月-2014年1月在湖南省人民医院住院的初次诊断的原发性肾病综合征患者46例为肾综组(NS组),同期健康体检者30例作为正常对照组(NC组)。收集两组受试者性别、年龄、血清白蛋白(AIB)、胆固醇(Chol).甘油三脂(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、尿蛋白定量、C-反应蛋白等相关临床资料,同时采用酶联免疫吸附法(ELISA法)检测了外周血清中HMGB-1.NF-κB的浓度。变量之间相关性分析采用Pearson相关性分析及多元线性逐步回归分析进行统计学分析。结果： 1.NS组HMGB-1.NF-κB的浓度明显高于NC组,差异有统计学意义(P0.01)。 2.Pearson相关分析提示：HMGB-1与尿蛋白定量、甘油三酯、总胆固醇、低密度脂蛋白、CRP呈正相关,与白蛋白呈负相关。NF-KB与尿蛋白定量、甘油三酯、总胆固醇、低密度脂蛋白呈正相关,与白蛋白呈负相关。多元线性回归分析显示：HMGB-1与尿蛋白定量独立相关,NF-κB与尿蛋白定量独立相关。 3.相关分析结果显示,HMGB-1与NF-κB之间呈正相关,相关系数=0.793,P0.01,差异有统计学意义。结论： 1.HMGB-1.NF-κB在原发性肾病综合征血清中表达水平上调,且两者呈正相关。 2.HMGB-1可能通过影响NF-κB在原发性肾病综合征的发病过程中发挥作用。 3.蛋白尿定量与原发性肾病综合征中炎症反应密切相关。
[Abstract]:Background: primary nephritic syndrome (PNS) is a common immune inflammatory disease. At present, the pathogenesis of primary nephrotic syndrome (PNS) is not very clear. Most scholars believe that immune-mediated and inflammatory injury play a leading role in the pathogenesis of primary nephrotic syndrome. A variety of inflammatory factors and immune responses are involved in the pathogenesis of nephropathy, and have a direct relationship with the progression of the disease. High mobility group protein high mobility group box-1 (HMGB-1) is a new type of inflammatory cytokine. It is widely found in eukaryotes and can be found both in cells and outside cells. At present, HMGB-1 is highly expressed in chronic renal insufficiency, lupus nephritis, diabetic nephropathy, acute renal dysfunction associated vasculitis and renal ischemia-reperfusion injury. In the study of signal transduction mechanism, it has been proved that HMGB-1 can interact with its receptor RAGE-Toll-like receptor, Toll-like receptor TLR2 / TLR4, by activating MAPK. Many pathways, such as MyD88, finally activate NF- 魏 B(nuclear factor-kappa, NF- 魏 B, and induce inflammation. Previous studies have confirmed that NF- 魏 B is highly expressed in patients with nephrotic syndrome and is involved in the occurrence and development of primary nephrotic syndrome. At present, the correlation between primary nephrotic syndrome and inflammatory factor HMGB-1 and its changes in serum of patients with primary nephrotic syndrome have not been reported at home and abroad. The correlation between NF-KB and primary nephrotic syndrome is analyzed. To further explore the role of its in the pathogenesis of primary nephrotic syndrome. Objective: to investigate the role of HMGB-1 in primary nephrotic syndrome (PNS) by measuring the concentration of HMGB-1.NF- 魏 B in peripheral serum of patients with primary nephrotic syndrome (PNS) and analyzing the relationship between HMGB-1.NF- 魏 B and Nephrotic syndrome. Methods: from January 2013 to January 2014, 46 primary nephrotic syndrome (PNS) patients in Hunan Provincial people's Hospital were selected as NS group and 30 healthy persons as normal control group. Sex, age, serum albumin AIBN and cholesterol Cholium were collected from the two groups. The serum HMGB-1.NF- 魏 B concentrations in serum were measured by enzyme linked immunosorbent assay (Elisa), including triglyceride (TGG), low density lipoprotein (LDL), high density lipoprotein (HDL) and urinary protein quantitative C-reactive protein (UQRP). Pearson correlation analysis and multiple linear stepwise regression analysis were used to analyze the correlation between variables. Results: The concentration of HMGB-1.NF- 魏 B in 1.NS group was significantly higher than that in NC group (P 0.01). 2.Pearson correlation analysis showed that: HMGB-1 was positively correlated with urinary protein, triglyceride, total cholesterol, low density lipoprotein CRP, negatively correlated with albumin. NF-KB was positively correlated with urinary protein, triglyceride, total cholesterol, low density lipoprotein. There was a negative correlation between albumin and albumin. Multiple linear regression analysis showed that there was an independent correlation between urine protein and urine protein, and between NF- 魏 B and urine protein. 3. The correlation analysis showed that there was a positive correlation between HMGB-1 and NF- 魏 B, and the correlation coefficient was 0.793p0.01, the difference was statistically significant. Conclusion: 1. The expression of HMGB-1.NF- 魏 B was up-regulated in the serum of primary nephrotic syndrome, and there was a positive correlation between them. 2.HMGB-1 may play a role in the pathogenesis of primary nephrotic syndrome by affecting NF- 魏 B. 3. The quantity of proteinuria is closely related to inflammatory reaction in primary nephrotic syndrome.
【学位授予单位】：湖南师范大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692

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