本文選題：TLR2 + TLR4　； 參考：《廣西醫(yī)科大學(xué)》2012年碩士論文

【摘要】：背景與目的：近年來,國內(nèi)糖尿病(diabetes mellitus, DM)患病率迅速升高。慢性大血管病變是糖尿病損害一個主要表現(xiàn),糖尿病動脈硬化(diabetic arteriosclerosis, DAS)是導(dǎo)致糖尿病患者死亡的重要原因之一。目前關(guān)于糖尿病及動脈粥樣硬化(athemsclemsis, AS)的發(fā)病機制還不是很明確,建立動物模型是實驗研究的基礎(chǔ)�！皳p傷反應(yīng)學(xué)說”認(rèn)為慢性炎癥過程和血脂代謝紊亂是AS的兩個主要特點。Toll樣受體(toll-like receptors, TLR)是近年來發(fā)現(xiàn)的天然免疫受體,它們可以通過廣泛地特異性地識別病原微生物,偶聯(lián)信號轉(zhuǎn)導(dǎo)途徑,并激活天然免疫細(xì)胞,最終導(dǎo)致一系列的免疫炎癥反應(yīng),有可能在DAS過程中發(fā)揮了重要的作用。本課題通過檢測糖尿病動脈粥樣硬化大鼠模型中TLR2、TLR4的表達(dá),探討TLR2及TLR4在糖尿病動脈粥樣硬化中起到的作用。 材料與方法：60只雄性SD大鼠隨機分為兩組,30只作為正常對照組,其余作為實驗對照組。用腹腔注射鏈脲佐菌素(streptozotocin, STZ)建立糖尿病動脈硬化大鼠模型。高糖高脂喂食后檢測血糖、總膽固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL);用逆轉(zhuǎn)錄聚合酶鏈反應(yīng)(retrovirus polymerase chain reaction, RT-PCR)方法檢測血液中TLR2及TLR4mRNA表達(dá)情況,并用凝膠掃描儀進(jìn)行電泳條帶強度分析；用免疫組織化學(xué)(immunohistochemical method) SP法檢測TLR2及TLR4在動脈組織中的蛋白表達(dá)情況；觀察動脈并取病變處,送廣西醫(yī)科大學(xué)試驗中心制作HE切片,光鏡下觀察動脈壁改變。 結(jié)果： 1.動物模型制造連續(xù)3次STZ注射完畢后,與對照組相比,模型組大鼠血糖明顯增高(P0.01)；高糖高脂喂食8周之后,模型組大鼠血脂四項,明顯增高(P0.01),造模成功率為93.33%(28/30)。 2. RT-PCR檢測28只糖尿病動脈硬化大鼠血漿中TLR2mRNA的陽性率為100%(28/28),相對應(yīng)的正常組大鼠血漿陽性率為40%(12/30),兩組比較均有顯著差異(P0.01)。檢測28只糖尿病動脈硬化大鼠血漿中TLR4mRNA的陽性率為100%(28/28),相對應(yīng)的正常組大鼠血漿陽性率為23.33%(7/30),兩組比較均有顯著差異(P0.01)。 3.免疫組化檢測28只糖尿病動脈硬化大鼠血漿中TLR2蛋白的陽性率為89.28%(25/28),對照組大鼠血漿陽性率為13.33%(4/30),兩組比較均有顯著差異(P0.01)。檢測28只糖尿病動脈硬化大鼠血漿中TLR4蛋白的陽性率為92.86%(26/28),對照組大鼠血漿陽性率為6.67%(2/30),兩紺比較均有顯著差異(P0.01)。 4.經(jīng)Spearmann、Pearson等級相關(guān)分析TLR2和TLR4的mRNA和蛋白表達(dá)水平呈正相關(guān)關(guān)系(P0.01)。 5.病理切片主動脈肉眼可見動脈管肥大,鏡下觀具有糖尿病動脈硬化的早期改變,如纖維組織增生、有核細(xì)胞增多,表層及中膜層結(jié)構(gòu)變疏松。 結(jié)論：研究結(jié)果顯示,TLR2和TLR4在糖尿病動脈硬化大鼠主動脈和血漿中高表達(dá),這種表達(dá)與高血糖及血脂代謝紊亂有關(guān)。對兩者的聯(lián)合檢測尤其是早期檢測有助于提早發(fā)現(xiàn)糖尿病動脈硬化改變,為以后的臨床治療提供一定的幫助。
[Abstract]:BACKGROUND & OBJECTIVE : In recent years , the prevalence of diabetes mellitus ( DM ) is increasing rapidly . The pathogenesis of diabetes and atherosclerosis is one of the most important causes of diabetes . Toll - like receptors ( TLR ) are two main characteristics of AS . Toll - like receptors ( TLR ) are two main characteristics of AS . Toll - like receptors ( TLR ) have played an important role in the pathogenesis of diabetes mellitus . Toll - like receptors ( TLR ) can play an important role in the process of DAS .

Materials and Methods : Sixty male SD rats were randomly divided into two groups , 30 were used as control group , and the rest were used as experimental control group . Blood glucose , total cholesterol ( TC ) , triglyceride ( TG ) , high density lipoprotein ( HDL ) and low density lipoprotein ( LDL ) were detected after high glucose and high fat feeding . The expression of TLR2 and TLR4 mRNA in blood was detected by reverse transcription polymerase chain reaction ( RT - PCR ) .
Immunohistochemical method was used to detect the expression of TLR2 and TLR2 in arterial tissue .
The artery was observed and the lesion was taken , HE section was produced at the experimental center of Guangxi Medical University , and the changes of arterial wall were observed under light microscope .

Results :

1 . The blood glucose of the model group was significantly higher than that of the control group ( P0.01 ) .
After 8 weeks of high glucose and high fat diet , the blood lipids in the model group increased significantly ( P0.01 ) , and the success rate of the model group was 93.33 % ( 28 / 30 ) .

2 . The positive rate of TLR2 mRNA in plasma of 28 diabetic arteriosclerosis rats was 100 % ( 28 / 28 ) and 40 % ( 12 / 30 ) respectively . The positive rate of TLR4 mRNA was 100 % ( 28 / 28 ) in 28 diabetic arteriosclerosis rats .

3 . The positive rate of TLR2 protein in plasma of 28 diabetic arteriosclerosis rats was 89.28 % ( 25 / 28 ) and 13.33 % ( 4 / 30 ) in control group .

4 . There was positive correlation between TLR2 and TLR2 mRNA and protein expression levels ( P0.01 ) .

5 . The vascular hypertrophy of the aorta is seen in the pathological section of the aorta , and the view of the mirror has the early change of the diabetic arteriosclerosis , such as fibrous tissue hyperplasia , the increase of nucleated cells , the change of the superficial layer and the middle membrane layer .

Conclusion : The results show that TLR2 and TLR2 are highly expressed in aorta and plasma of diabetic arteriosclerosis rats . This expression is related to hyperglycemia and lipid metabolism disorder . Combined detection of both is helpful for early detection of diabetic arteriosclerosis and provides some help for later clinical treatment .
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R587.1;R-332

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