本文選題：TLR4 + TRAIL　； 參考：《皖南醫(yī)學(xué)院》2017年碩士論文

【摘要】：目的:通過(guò)檢測(cè)TLR4和TRAIL在外周血單核細(xì)胞中表達(dá)水平的高低,同時(shí)檢測(cè)血清中各種細(xì)胞因子的表達(dá)量,全面的分析TLR4和TRAIL與各細(xì)胞因子的相關(guān)性,結(jié)合多方面的結(jié)果,將有助于進(jìn)一步探討糖尿病腎病(DN)發(fā)病機(jī)制,有望成為DN早期診斷與愈后判斷的指標(biāo),為DN的治療提理論供依據(jù)。方法:收集2015年9月至2016年6月的糖尿病(DM)及DN患者各42例,并且全部符合相關(guān)診斷標(biāo)準(zhǔn)和排除標(biāo)準(zhǔn),同時(shí)收集正常對(duì)照人群(CONTROL)42例;每個(gè)研究對(duì)象分別采血2管,提取血清、血漿,并分離抗凝管中的外周血單核細(xì)胞,使用qPCR的方法檢測(cè)單核細(xì)胞中的TLR4mRNA及TRAILmRNA的含量;使用ELISA測(cè)定所收集血清中各類細(xì)胞因子的濃度;病例組與對(duì)照組之間患者的一般情況及所測(cè)量的生化指標(biāo)采用方差分析或χ2檢驗(yàn);各組間細(xì)胞因子之間的濃度差異采用方差分析及Welch檢驗(yàn)方法,因子間的相關(guān)性分析采用Pearson相關(guān)或Spearman's相關(guān)方法。結(jié)果:DN組、DM組、CONTROL組人群在性別、吸煙、飲酒與體質(zhì)指數(shù)(BMI)方面的分布情況相近,未發(fā)現(xiàn)差異有統(tǒng)計(jì)學(xué)意義(P0.05),DN組患者在勞動(dòng)強(qiáng)度方面低于CONTROL組研究對(duì)象,而在年齡上高于CONTROL組人群,DM組患者心理緊張的人數(shù)多于CONTROL組,CONTROL組初高中的人數(shù)多于DN組和DM組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。DN組、DM組和CONTROL組在總膽固醇(TC)、低密度脂蛋白(LDL-C)、總膽紅素、直接膽紅素、谷丙轉(zhuǎn)氨酶(ALT)、尿素氮方面差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);在空腹血糖(GLU)、收縮壓、舒張壓、甘油三酯(TG)、肌酐及尿酸方面,DN組的含量均高于CONTROL組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。在高密度脂蛋白(HDL-C)及谷草轉(zhuǎn)氨酶(AST)方面,DN組的含量低于CONTROL組,差異有統(tǒng)計(jì)學(xué)意義(P0.05);DN組與DM組的焦慮、抑郁、睡眠質(zhì)量評(píng)分要高于CONTROL組(P0.05);單因素Logistic回歸分析顯示年齡、焦慮、抑郁、睡眠、收縮壓和舒張壓是DN的危險(xiǎn)因素,而勞動(dòng)程度、文化程度及HDL-C是DN的保護(hù)因素(P0.05);多因素非條件Logistic回歸顯示睡眠質(zhì)量與TG則是DN的危險(xiǎn)因素,勞動(dòng)強(qiáng)度與HDL-C是DN的保護(hù)因素(P0.05)。三組間TLR4mRNA、TRAILmRNA的表達(dá)量差異均有統(tǒng)計(jì)學(xué)意義(P0.01),DN組、DM組及CONTROL組在TLR4mRNA的表達(dá)量方面未發(fā)現(xiàn)差異(P0.05),DN組、DM組中TRAILmRNA的表達(dá)量要明顯低于CONTROL組(P0.01);DN在IL-1、IL-6、TNF-α、MCP-1、NF-κB、hs-CRP方面表達(dá)量均高于CONTROL組,sTRAIL的濃度低于CONTROL組(P0.05),DN組中因子IL-1、TNF-a、MCP-1的濃度要高于DM組(P0.05)。分層分析顯示三組間在≤50歲研究對(duì)象中,DN組中IL-1、IL-6、MCP-1的含量要高于CONTROL組(P0.05),sTRAIL、TRAILmRNA含量低于CONTROL組(P0.05),并且IL-6、MCP-1的表達(dá)測(cè)定量也高于DM組(P0.05);三組間在51-60歲研究對(duì)象中,DN組中IL-1、MCP-1的含量高于CONTROL組(P0.05),TRAILmRNA含量低于CONTROL組(P0.05),并且IL-1、MCP-1的含量高于DM組(P0.05);三組間在60歲研究對(duì)象中,DN組中IL-1、TNF-α、MCP-1的濃度均高于DM組、CONTROL組,而TRAILmRNA的表達(dá)量低于CONTROL組(P0.05)。Spearman's相關(guān)性分析可以看出TLR4mRNA與sTRAIL呈負(fù)相關(guān)(r=-0.188,P0.05),與其他因子則未發(fā)現(xiàn)相關(guān)性的存在(P0.05);TRAILmRNA則與IL-1、TNF-α、MCP-1、NF-κB、hs-CRP均呈負(fù)相關(guān)(P0.05),與sTRAIL的呈正相關(guān)(r=0.281,P0.05);對(duì)TLR4mRNA進(jìn)行組間的相關(guān)性分析顯示TLR4mRNA在DN組與DM組都與TRAILmRNA呈正相關(guān)(r=0.363,P0.05;r=0.540,P0.05)。TRAILmRNA在DN組中與NF-κB呈負(fù)相關(guān)(r=-0.422,P0.05);在≤50歲年齡段的研究對(duì)象中,TRAILmRNA與hs-CRP呈負(fù)相關(guān)(r=-0.346,P0.05),與sTRAIL呈正相關(guān)(r=0.394,P0.05);在60歲年齡段的研究對(duì)象中與IL-1呈負(fù)相關(guān)(r=-0.407,P0.05)。TLR4mRNA在DN組中且年齡60歲研究對(duì)象中與TNF-α呈負(fù)相關(guān)(r=-0.442,P0.05),與TRAILmRNA呈正相關(guān)(r=0.498,P0.05)。TRAILmRNA在DN組中且年齡為≤50歲的研究對(duì)象中顯示與TNF-α呈正相關(guān)(r=0.749,P0.05),在DN組中≤50歲及51-60歲年齡組均與NF-κB呈負(fù)相關(guān)(r=-0.734,P0.05;r=-0.607,P0.05);在DN組中的年齡為≤50歲組中與hs-CRP呈負(fù)相關(guān)(r=-0.714,P0.05)。結(jié)論:在DN患者、DM患者及CONTROL人群中,DN患者血清中IL-1、IL-6、TNF-α、NF-κB、MCP-1、hs-CRP均高于CONTROL組,DN人群血清中sTRAIL的含量要低于DM組及CONTROL組;DN組及DM組外周血中TRAILmRNA的表達(dá)量均顯著低于CONTROL組;TRAIL與TNF-α有著相似的途徑,在體內(nèi)的表達(dá)均受到年齡因素的影響,TNF-α在機(jī)體內(nèi)表現(xiàn)為促炎因子,TRAIL在本研究中起抗炎作用,但在≤50歲的DN患者中與TNF-α存在高度的正相關(guān);TRAILAmRNA的表達(dá)量與血清中L-1、IL-6、TNF-α、NF-κB、MCP-1、hs-CRP呈負(fù)相關(guān)。
[Abstract]:Objective: to detect the expression of TLR4 and TRAIL in peripheral blood mononuclear cells, to detect the expression of various cytokines in the serum, and to analyze the correlation between TLR4 and TRAIL and the various cytokines in a comprehensive way. Combined with many results, it will be helpful to further explore the pathogenesis of diabetic nephropathy (DN) and be expected to be the early diagnosis of DN. The index of judgment and judgment was based on the theory of DN. Methods: 42 cases of diabetes (DM) and DN patients from September 2015 to June 2016 were collected and all were in accordance with the relevant diagnostic criteria and exclusion criteria, and 42 cases of normal control group (CONTROL) were collected. 2 tubes were collected from each study, and serum, plasma, and isolation were extracted, respectively. The content of TLR4mRNA and TRAILmRNA in mononuclear cells was detected by qPCR in the peripheral blood mononuclear cells in the coagulant tube; the concentration of all kinds of cytokines in the collected serum was measured by ELISA; the general situation of the patients with the case group and the control group and the measured variance analysis of the biochemical indexes or the chi 2 test; the cytokine between each group The difference of concentration was analyzed by variance analysis and Welch test, and the correlation analysis between factors adopted Pearson related or Spearman's related methods. Results: the distribution of sex, smoking, drinking and body mass index (BMI) in group DN, DM and CONTROL group was similar, no statistical difference was found (P0.05), and the patients in group DN were in labor. The intensity is lower than the CONTROL group, and the age of group CONTROL is higher than that of group DM, and the number of patients in group DM is more than that of group CONTROL. The number of early and high school in group CONTROL is more than group DN and DM, the difference is statistically significant (P0.05).DN group, DM group and CONTROL group in total bile sterol (TC), low density lipoprotein, total bilirubin, direct There was no significant difference in bilirubin, ALT, and urea nitrogen (P0.05). In the fasting blood glucose (GLU), systolic pressure, diastolic pressure, triglyceride (TG), creatinine and uric acid, the content of DN group was higher than that of group CONTROL (P0.05). The content of DN group was low in high density lipoprotein (HDL-C) and glutamic pyruvic aminotransferase (AST). In group CONTROL, the difference was statistically significant (P0.05); the anxiety, depression, and sleep quality score of group DN and DM were higher than that of group CONTROL (P0.05); single factor Logistic regression analysis showed that age, anxiety, depression, sleep, systolic and diastolic pressure were the risk factors of DN, and the degree of labor, degree of education and HDL-C were the protective factors of DN (P0.05); multiple factors Non conditional Logistic regression showed that sleep quality and TG were risk factors for DN, labor intensity and HDL-C were the protective factors of DN (P0.05). There were significant differences in the expression of TLR4mRNA and TRAILmRNA between the three groups (P0.01). There was no difference in the expression of DN, DM and CONTROL groups. The amount of DN in IL-1, IL-6, TNF- alpha, MCP-1, NF- kappa B, hs-CRP is higher than that of the CONTROL group, and the concentration of sTRAIL is lower than that of the CONTROL group. The content of sTRAIL and TRAILmRNA was higher than that of group CONTROL (P0.05), and the content of TRAILmRNA was lower than that of CONTROL group (P0.05), and the expression of IL-6 and MCP-1 was higher than that of the DM group (P0.05). The content of IL-1 in the three group was higher than that in the group of DN, and the content was lower than that of the group. 5); among the three groups, the concentration of IL-1, TNF-, and MCP-1 in group DN was higher than that in group DM and CONTROL, while the expression of TRAILmRNA was lower than that of CONTROL group (P0.05).Spearman's. TNF- alpha, MCP-1, NF- kappa B, hs-CRP are negatively correlated (P0.05), and are positively correlated with sTRAIL (r=0.281, P0.05). In the study, TRAILmRNA was negatively correlated with hs-CRP (r=-0.346, P0.05), and was positively correlated with sTRAIL (r=0.394, P0.05). In the 60 year old age group, the negative correlation with IL-1 (r=-0.407, P0.05).TLR4mRNA was in the DN group and the 60 year old subjects were negatively correlated with the IL-1. AILmRNA in group DN and age younger than 50 years old showed positive correlation with TNF- alpha (r=0.749, P0.05). In group DN, there was a negative correlation with NF- kappa B (r=-0.734, P0.05; r=-0.607, P0.05) in the group of 50 and 51-60 years old. In the CONTROL population, the serum levels of IL-1, IL-6, TNF- a, NF- kappa B, MCP-1, and hs-CRP were all higher than those of the CONTROL group. The content of sTRAIL in the serum of DN population was lower than that in the group and group. The effect of TNF- alpha in the body is proinflammatory factor, and TRAIL plays an anti-inflammatory role in this study, but there is a positive correlation with TNF- alpha in DN patients less than 50 years old; the expression of TRAILAmRNA is negatively correlated with L-1, IL-6, TNF- a, NF- kappa B, MCP-1, hs-CRP in serum.
【學(xué)位授予單位】：皖南醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R587.2;R692.9

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 吳琛;肖建中;趙文惠;路曉;王娜;Telemed China研究組;;文化程度與北京社區(qū)2型糖尿病患者心血管病危險(xiǎn)因素達(dá)標(biāo)率及微血管并發(fā)癥患病率的相關(guān)性研究[J];中國(guó)糖尿病雜志;2016年09期

2 鄭健宇;;糖尿病腎病患者高密度脂蛋白抗炎能力的分析[J];當(dāng)代醫(yī)學(xué);2016年21期

3 劉憲紅;豐慧慧;牛金葆;杜麗霞;吳紹華;;2型糖尿病患者合并焦慮情緒的調(diào)查分析[J];臨床合理用藥雜志;2016年05期

4 陳佳;何婭妮;;TRAIL及其受體在腎臟疾病的研究進(jìn)展[J];中華腎病研究電子雜志;2015年04期

5 周劏;董萍;李晗;毛維維;韓冬梅;鞏偉偉;馮波;;糖尿病腎臟疾病患者外周血單核細(xì)胞TLR4基因表達(dá)及其與炎性因子的關(guān)系[J];山東醫(yī)藥;2015年20期

6 華春芬;王飛;葉小君;;成人2型糖尿病危險(xiǎn)因素的現(xiàn)況研究[J];浙江預(yù)防醫(yī)學(xué);2015年01期

7 管凌志;;2型糖尿病腎病患者血清MCP-1、NF-κB水平變化及臨床意義[J];局解手術(shù)學(xué)雜志;2014年04期

8 曲韶玲;;糖尿病腎病病人血清TNF-α、抵抗素和尿微量清蛋白檢測(cè)[J];齊魯醫(yī)學(xué)雜志;2014年02期

9 李夢(mèng)倩;胡勃;孫茜;鈔雪林;湯佳珍;袁也豐;;糖尿病腎病患者焦慮、抑郁情況及生存質(zhì)量調(diào)查研究[J];江西醫(yī)藥;2014年01期

10 鄭利平;李生;;檢測(cè)Hcy、FFA、hs-CRP在2型糖尿病腎病患者中的意義[J];中華全科醫(yī)學(xué);2013年05期

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