本文選題：糖尿病 + 端粒��； 參考：《河北大學(xué)》2017年碩士論文

【摘要】：背景:糖尿病是一種以高血糖為病理特征的代謝性疾病,若體內(nèi)長期維持高血糖狀態(tài)會引起一系列的并發(fā)癥,例如:腎臟、肝臟、心臟、血管、眼等的損傷,對人體健康產(chǎn)生非常嚴(yán)重的影響。糖尿病的發(fā)病率也呈逐年上升狀態(tài),并且,全球沒有非常有效的醫(yī)療手段治愈此類疾病。糖尿病患病初始沒有任何表征,當(dāng)病人到醫(yī)院就診時,大部分胰島細(xì)胞已經(jīng)失去功能,只能依靠藥物維持血糖平衡。糖尿病早期發(fā)現(xiàn)、早期治療成為當(dāng)今的一項研究熱點,通過分子生物學(xué)手段對外周血白細(xì)胞端粒長度與端粒酶活性進(jìn)行檢測以探討白細(xì)胞端粒長度變化、端粒酶活性變化與糖尿病的相關(guān)性。方法:提取30例1型糖尿病(T1DM)、60例2型糖尿病(T2DM)、40例2型伴動脈硬化糖尿病(DAS)患者外周血白細(xì)胞基因組DNA,利用實時熒光定量PCR的方法檢測基因組DNA的端粒長度,以36B4基因作為對照,檢測不同分型糖尿病間以及糖尿病患者與正常健康人間的端粒長度變化情況。從而探究糖尿病對人類外周血白細(xì)胞端粒長度的影響;利用多元線性回歸分析探究影響端粒長度的具體因素。分別提取40例T1DM患者、80例T2DM患者的外周血白細(xì)胞與血漿,利用TRAP-PCR的方法檢測白細(xì)胞與血漿中是否存在端粒酶活性;再利用熒光定量PCR的方法檢測端粒酶的活性;從而探究糖尿病對外周血白細(xì)胞、血漿的端粒酶活性影響情況,利用多元線性回歸分析探究影響端粒酶活性的主要因素。結(jié)果:建立了檢測端粒長度與端粒酶活性的可靠辦法。T1DM、T2DM、DAS患者外周血白細(xì)胞端粒長度均小于健康對照(NC)組(P0.05);在不同分型的糖尿病對比中T1DM組端粒長度短于T2DM組與DAS組,DAS組比T2DM組更短。通過多元線性回歸分析得到:在T1DM組中,年齡與白細(xì)胞端粒長度呈負(fù)相關(guān)(P0.05);T2DM組中,年齡、BMI與白細(xì)胞端粒長度呈負(fù)相關(guān)(P0.05);DAS組中,BMI、患病時間與端粒長度呈負(fù)相關(guān)(P0.05)。在糖尿病患者外周血白細(xì)胞、血漿的端粒酶活性檢測試驗中,根據(jù)TRAP-PCR與RT-q PCR的結(jié)果顯示,在T1DM組、T2DM組與NC組中的外周血血漿中并沒有發(fā)現(xiàn)端粒酶活性。在外周血白細(xì)胞中均發(fā)現(xiàn)了端粒酶活性,T1DM患者的外周血白細(xì)胞端粒酶活性與T2DM患者均顯著高于NC組的(P0.05);并且T1DM患者的端粒酶活性高于T2DM患者(P0.05)。多元線性回歸分析顯示:在T2DM組中,性別與吸煙狀況與白細(xì)胞端粒酶活性有顯著相關(guān)性(P0.05),得到男性與吸煙患者的白細(xì)胞端粒酶活性強于女性與不吸煙者。結(jié)論:糖尿病患者的外周血白細(xì)胞端粒長度明顯短于正常人,并且T1DM患者的端粒長度顯著短于T2DM;在2型糖尿病的對比中,DAS患者的端粒長度明顯短于T2DM�；颊叩哪挲g、患病時間、BMI值與端粒長度的縮短有密切的關(guān)系。在T1DM與T2DM患者的外周血血漿中都沒有發(fā)現(xiàn)端粒酶活性存在。T1DM與T2DM患者的外周血白細(xì)胞端粒酶活性顯著高于正常人;并且,T1DM患者的白細(xì)胞端粒酶活性高于T2DM患者。在T2DM組中發(fā)現(xiàn)性別與吸煙狀況與白細(xì)胞端粒酶活性有顯著相關(guān)性。糖尿病對于外周血白細(xì)胞的端粒長度、端粒酶活性均有明顯影響;對于二者的相關(guān)檢查可能對于糖尿病的早發(fā)現(xiàn)、早治療提供合理依據(jù)。
[Abstract]:Background: diabetes is a metabolic disease characterized by hyperglycemia. The long-term maintenance of hyperglycemia in the body causes a series of complications, such as kidney, liver, heart, blood vessels, and eye injuries, which have a very serious impact on human health. The incidence of glycuria is also rising year by year, and the world has not It is very effective to cure such diseases. There is no sign of diabetes at the beginning. When the patient goes to the hospital, most of the islet cells have lost their function and can only rely on drugs to maintain the blood sugar balance. Early diabetes has been found, and early treatment has become a hot spot of research, by means of molecular biological means. Telomere length and telomerase activity were detected to investigate the changes of telomere length and telomerase activity and the correlation between telomerase activity and diabetes. Methods: 30 cases of type 1 diabetes mellitus (T1DM), 60 cases of type 2 diabetes (T2DM), 40 cases of type 2 atherosclerosis diabetes (DAS) patients with peripheral blood leukocyte genome DNA were used, and real-time quantitative PCR was used. The telomere length of genomic DNA was detected and the 36B4 gene was used as the control to detect the change of telomere length between diabetic patients and diabetic patients and normal healthy people. The effect of diabetes on the telomere length of human peripheral blood white blood cells was explored, and the multielement linear regression analysis was used to explore the effect of telomere length. Body factors. The peripheral blood leukocytes and plasma were extracted from 40 patients with T1DM and 80 patients with T2DM respectively. The telomerase activity in white cells and plasma was detected by TRAP-PCR, and the activity of telomerase was detected by fluorescence quantitative PCR, and the telomerase activity in peripheral blood leukocytes and plasma was investigated. The main factors affecting telomerase activity were analyzed by multiple linear regression analysis. Results: a reliable method for detecting telomere length and telomerase activity was established. The telomere length of peripheral blood leukocytes in patients with T2DM and DAS was less than that of the healthy control group (NC) (P0.05), and the telomere length of group T1DM in different types of diabetes was shorter than that of group T2DM and D (T2DM and D). Group AS, group DAS was shorter than group T2DM. By multiple linear regression analysis, age was negatively correlated with telomere length in leukocyte (P0.05) in group T1DM; in group T2DM, age, BMI was negatively correlated with telomere length of white blood cells (P0.05); in group DAS, BMI, negative correlation with end grain length (P0.05). In diabetic patients, peripheral blood leukocytes, plasma In the test of telomerase activity, according to the results of TRAP-PCR and RT-q PCR, the telomerase activity was not found in the T1DM group, in the peripheral blood plasma of the T2DM group and the NC group. The telomerase activity was found in the peripheral blood leukocytes, and the activity of the peripheral leukocyte telomeric enzyme in the peripheral blood of the T1DM patients was significantly higher than that of the NC group (P0.05). The telomerase activity of T1DM patients was higher than that of T2DM patients (P0.05). Multiple linear regression analysis showed that in group T2DM, there was a significant correlation between sex and smoking status and leukocyte telomerase activity (P0.05). The telomerase activity of white blood cells in male and smoking patients was stronger than that of women and non smokers. Conclusion: the peripheral blood of diabetic patients is white. Telomere length was significantly shorter than that of normal people, and the telomere length of T1DM patients was significantly shorter than that of T2DM. In the contrast of type 2 diabetes, the telomere length of DAS patients was significantly shorter than the age of T2DM. patients, the time of the disease, the BMI value was closely related to the shortened telomere length. No telomerase was found in the peripheral blood plasma of the patients with T1DM and T2DM. Telomerase activity in peripheral blood leukocytes in patients with active.T1DM and T2DM was significantly higher than that of normal people; and the telomerase activity of leukocytes in T1DM patients was higher than that of T2DM patients. In T2DM group, there was a significant correlation between sex and smoking status and telomerase activity in leukocytes. Telomere length and telomerase activity in peripheral blood leukocytes were found in diabetic patients. There is a significant effect; the relevant examination of the two may provide a reasonable basis for early detection and early treatment of diabetes.

【學(xué)位授予單位】：河北大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R587.1

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