本文選題：糖尿病 + 糖尿病并發(fā)癥　； 參考：《河北醫(yī)科大學》2015年碩士論文

【摘要】：目的:糖尿病(diabete mellitus,DM)是一種常見病,其常見的并發(fā)癥主要發(fā)生在微血管和大血管,如糖尿病腎病、視網(wǎng)膜病、冠心病等。是糖尿病致傷、致殘的主要原因。目前對并發(fā)癥發(fā)病機制的研究較多,但近些年慢性炎癥反應在并發(fā)癥中的作用受關注。其中TLR4(Toll1ike receptor4,TLR4)這一普遍存在于多種免疫細胞的模式識別受體介導的炎癥激活可能與DM并發(fā)癥中的炎癥反應有關。已知TLR4表達于巨噬細胞等固有性免疫細胞表面,糖尿病發(fā)生時,其內(nèi)源性配體如熱休克蛋白60(HSP60)、高遷移率族蛋白1(HMGBI)增加,可激活TLR4,誘導炎癥反應。且我們前期臨床和實驗研究中均證實高糖狀態(tài)下多種細胞TLR4的表達顯著升高,與其相關的炎癥因子IL-1β和TNF-α等的表達也升高,但是TLR4在其它臟器的表達及其相關炎癥因子的作用尚未完全清楚。因此,本課題擬制備DM大鼠模型,測定不同組織如肝臟、心臟和腎臟的TLR4及其相關炎癥因子IL-1β和TNF-α的表達,以及大鼠各組織炎癥浸潤的狀態(tài),全面了解DM狀態(tài)下多臟器的炎癥反應狀態(tài),進一步探討DM的并發(fā)癥的發(fā)生機制,為DM并發(fā)癥的抗炎治療提供實驗依據(jù)。方法:1制備糖尿病大鼠模型:SD雄性大鼠腹腔注射STZ(鏈脲佐菌素),72h后取尾靜脈血測定血糖,兩次檢測濃度均大于16.7mmol/L時為造模成功。糖尿病實驗組大鼠和正常對照組大鼠各10只。2實驗方法2.1檢測各器官TLR4及其相關炎癥因子m RNA的表達:造模12周后取大鼠的腎臟、心臟、肝臟組織,Real-time PCR方法檢測TLR-4、TNF-α和IL-1β表達水平。2.2檢測各組織器官炎癥浸潤狀態(tài):制備腎臟、心臟、肝臟的組織切片,HE染色檢測炎癥各組織的炎癥細胞。3統(tǒng)計學方法:采用Excel和SPSS13.0統(tǒng)計學軟件進行數(shù)據(jù)處理分析,數(shù)據(jù)以平均值±標準差表示,均數(shù)用獨立樣本t檢驗來比較組間差異性,P0.05為有統(tǒng)計學意義。結(jié)果:1成功建立了Ⅱ型糖尿病大鼠模型。2 TLR4 m RNA的表達水平Real-time PCR結(jié)果顯示,大鼠心臟、肝臟和腎臟的TLR4表達如下,心臟內(nèi)TLR4m RNA表達水平,在健康對照組和DM組中分別為1.104±0.189和1.079±0.503,健康對照組與DM組之間無統(tǒng)計學差異;肝臟內(nèi)TLR4 m RNA的表達水平,健康對照組和DM組分別為0.933±0.275和8.899±1.769,TLR4 m RNA的表達水平明顯高于對照組;腎臟內(nèi)TLR4 m RNA的表達水平,健康對照組和DM組分別為1.032±0.125和2.766±0.663,DM組的TLR4 m RNA水平相比健康對照組明顯升高。3 IL-1βm RNA的表達水平Real-time PCR結(jié)果顯示,心臟的IL-1βm RNA表達健康對照組和DM組分別為1.025±0.263和1.120±0.311,健康對照組與DM組之間無顯著差異;肝臟的IL-1βm RNA表達,健康對照組和DM組分別為1.175±0.275和3.940±0.958,DM組顯著高于健康對照組;腎臟的IL-1βm RNA健康對照組和DM組分別為1.125±0.222和6.900±1.700,DM組顯著高于健康對照組。4 TNF-αm RNA的表達水平心臟的TNF-αm RNA表達在健康對照組和DM組分別為1.075±0.359和1.080±0.449,健康對照組與DM組之間無顯著差異;肝臟的TNF-αm RNA表達在健康對照組和DM組分別為1.150±0.311和4.060±1.097,DM組顯著高于健康對照組;腎臟的TNF-αm RNA表達在健康對照組和DM組分別為1.050±0.208和10.38±1.753,DM組顯著高于健康對照組。5 HE染色結(jié)果心臟、肝臟、腎臟組織HE染色結(jié)果顯示:12w時,與健康對照組相比,DM組心臟心肌纖維肥大,間質(zhì)水腫,血管周有炎細胞;DM組肝臟脂肪炎癥細胞浸潤多于對照組;DM組腎臟間質(zhì)大量炎癥細胞浸潤。結(jié)論:1 TLR4 m RNA在DM大鼠肝臟、腎臟中有高表達,而TLR4 m RNA在心臟中的表達,DM組和對照組間不存在統(tǒng)計學差異。2 DM組大鼠在肝臟和腎臟中的IL-1βm RNA、TNF-αm RNA表達均顯著升高,而在心臟無顯著變化。3 DM組心臟、肝臟和腎臟均出現(xiàn)炎癥細胞浸潤。
[Abstract]:Objective: diabete mellitus (DM) is a common disease. The common complications are mainly in microvascular and large blood vessels, such as diabetic nephropathy, retinopathy, coronary heart disease and so on. It is the main cause of diabetes injury and disability. There are many studies on the pathogenesis of complications, but the chronic inflammatory reaction in recent years is in the complications. It is concerned. TLR4 (Toll1ike receptor4, TLR4), a pattern recognition receptor commonly found in many immune cells, may be associated with inflammatory responses in DM complications. The known TLR4 is expressed on the surface of a solid immune cell, such as macrophages, and its endogenous ligand such as heat shock protein 60 (HSP60) occurs when diabetes occurs. The high mobility group protein 1 (HMGBI) increased and activated TLR4 to induce the inflammatory response. In our previous clinical and experimental studies, the expression of TLR4 in a variety of cells in high glucose state was significantly increased, and the expression of the related inflammatory factors, IL-1 beta and TNF- a, was also increased, but it was the expression of TLR4 in other organs and related inflammatory factors. The role of DM rat is not completely clear. Therefore, we prepare a rat model to determine the expression of TLR4 and its related inflammatory factors IL-1 beta and TNF- alpha in different tissues such as liver, heart and kidney, as well as the state of inflammatory infiltration of various tissues in rats, to understand the inflammatory reaction state of multiple organs in DM state, and to further explore the occurrence of the complications of DM. Mechanism to provide experimental basis for the anti inflammatory treatment of DM complications. Methods: 1 the diabetic rat model was prepared: SD male rats were intraperitoneally injected with STZ (streptozotocin), 72h after 72h was used to measure blood sugar, and the concentration was greater than 16.7mmol/L. The experimental group of diabetic test group and normal control group of rats each had 10.2 experimental methods 2 .1 was used to detect the expression of TLR4 and related inflammatory factors m RNA in each organ: after 12 weeks of modeling, the kidney, heart, liver tissue, TLR-4, TNF- A and IL-1 beta expression level.2.2 were used to detect the inflammatory infiltration of tissues and organs by Real-time PCR method: the tissue sections of the kidneys, heart and liver were prepared, and the inflammation of the tissues was detected by HE staining. .3 statistical method: using Excel and SPSS13.0 statistics software for data processing and analysis, the data were expressed as mean standard deviation, and the average number was compared with the independent sample t test. The P0.05 was statistically significant. Results: 1 the expression level of.2 TLR4 m RNA in type II diabetic rat model was successfully established by Real-time PCR results. The expression of TLR4 in the heart, liver and kidney of the rat was as follows. The expression level of TLR4m RNA in the heart was 1.104 + 0.189 and 1.079 + 0.503 in the healthy control group and the DM group respectively. There was no statistical difference between the healthy control group and the DM group. The expression level of TLR4 m RNA in the liver was 0.933 + 0.275 and 8.899 + 1.769 and TLR4 m in the healthy group and the DM group, respectively. The expression level of RNA was significantly higher than that in the control group, and the expression level of TLR4 m RNA in the kidney was 1.032 + 0.125 and 2.766 + 0.663 in the healthy control group and DM group respectively. The TLR4 m RNA level in the DM group was significantly higher than that in the healthy control group, and the expression level of.3 IL-1 beta m was significantly higher than that of the healthy control group. There was no significant difference between 1.025 + 0.263 and 1.120 + 0.311 in the healthy control group and the DM group. The expression of IL-1 beta m RNA in the liver was 1.175 + 0.275 and 3.940 + 0.958 in the healthy control group and DM group, and the DM group was significantly higher than the healthy control group; the IL-1 beta m RNA healthy control group and the DM component of the kidney were 1.125 + 0.222 and 6.900 + 1.700, and the DM group was significant Gao Yujian The expression of TNF- alpha m RNA in the expression level of.4 TNF- alpha m RNA in the control group was 1.075 + 0.359 and 1.080 + 0.449 in the healthy control group and DM group respectively. There was no significant difference between the healthy control group and the DM group. The TNF- alpha m RNA expression in the liver was 1.150 + 0.311 and 4.060 + 1.097 respectively in the healthy control group and the healthy control group, and the group was significantly higher than the healthy control group. The expression of TNF- alpha m RNA in the kidney was 1.050 + 0.208 and 10.38 + 1.753 in the healthy control group and the DM group respectively. The DM group was significantly higher than the healthy control group with.5 HE staining results. The liver and renal tissue HE staining showed that when 12W, the cardiac muscle fiber was large, interstitial edema, vascular peripheral inflammatory cells, and DM group liver fat was compared with the healthy control group. The infiltration of inflammatory cells in the renal interstitium in DM group was more than that in the control group. Conclusion: 1 TLR4 m RNA is highly expressed in the liver of DM rats, and the expression of TLR4 m RNA in the heart, there is no statistical difference between the DM group and the control group, and the IL-1 beta in the liver and kidney of the.2 DM group is significantly elevated. There was no significant change in heart. Inflammatory cells infiltrated in heart, liver and kidneys of.3 DM group.
【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R587.1

【參考文獻】

相關期刊論文 前4條

1 王海瀾;楊濤;賀麗;黃望香;;2型糖尿病與炎性細胞因子相關性的臨床研究[J];中國煤炭工業(yè)醫(yī)學雜志;2008年05期

2 郭宗明;VEGF與惡性血液病的關系[J];國外醫(yī)學(生理、病理科學與臨床分冊);2004年02期

3 劉穎慧;TNF-α與糖尿病腎病[J];國外醫(yī)學.內(nèi)分泌學分冊;2002年04期

4 高洪偉,洪天配,李瓊芳;煙酰胺對白細胞介素1β所致胰島損傷的防護作用及其機制[J];中華醫(yī)學雜志;1996年07期

，

本文編號：1911230