本文選題：糖尿病 + 神經(jīng)調(diào)節(jié)蛋白1��； 參考：《廣西醫(yī)科大學(xué)》2015年碩士論文

【摘要】：研究背景和目的：研究發(fā)現(xiàn)至少65%糖尿病(DM)患者死亡與冠狀動(dòng)脈動(dòng)脈硬化性心臟病有關(guān)。冠狀動(dòng)脈血管旁路移植手術(shù)(CABG)是治療終末期冠脈嚴(yán)重病變的重要手段。盡管多種動(dòng)脈移植物相繼被應(yīng)用于CABG中,但因其來源不足在臨床應(yīng)用中仍受到很大限制。迄今大隱靜脈仍是最為常用的血管橋。而應(yīng)用大隱靜脈橋進(jìn)行CABG合并糖尿病術(shù)后遠(yuǎn)期心肌梗死和死亡率顯著上升。DM靜脈橋術(shù)后內(nèi)膜增生導(dǎo)致再狹窄的原因及作用機(jī)制尚未可知,同時(shí)亦無理想的防治方法。最近研究表明NRG-1在糖尿病心血管疾病表達(dá)明顯下調(diào),而且NRG-1能保護(hù)血管內(nèi)皮細(xì)胞和抑制平滑肌增殖、遷移,亦能減少氧化應(yīng)激。因此探討NRG-1是否參與DM靜脈橋再狹窄的過程是很有必要的。本研究旨在動(dòng)物上建立DM靜脈橋模型,探究靜脈橋在DM環(huán)境下內(nèi)膜增厚情況以及NRG-1表達(dá)變化,有望為DM患者血管橋再狹窄的預(yù)防及治療提供新的途徑。研究方法：1、隨機(jī)選用8-10周齡雄性(Sprague-Dawley rats)SD大鼠50只,體重200-220g,給予標(biāo)準(zhǔn)大鼠飼料,隨機(jī)分為兩組：糖尿病組(DM組,n=25)和正常對(duì)照組(NC組,n=25),DM組給予大劑量STZ(55mg/kg)腹腔注射建立糖尿病大鼠模型；NC組給予等體積生理鹽水腹腔注射。3天后尾靜脈采血測(cè)空腹血糖16.7mmol/L的大鼠納入糖尿病模型組。2、選取造模成功的DM大鼠(DM組)與正常大鼠(NC組)隨機(jī)分為3組,分別為DM大鼠0周(DM-OW、2周(DM-2W,n=6)、4周(DM-4W,n=6)及正常組0周(NC-OW,n=6)、2周(NC-2W,n=6)、4周(NC-4W,n=6), STZ注射1周后,采用改良cuff管法對(duì)所有大鼠建立自體頸外靜脈移植頸總動(dòng)脈模型。3、分別取兩組0周、2周、4周的血管橋行病理檢測(cè),測(cè)量?jī)山M血管橋管壁的內(nèi)、中膜厚度并比較二者的差別。免疫組化檢測(cè)PCNA和NRG1的表達(dá)情況,同時(shí)利用Western blot測(cè)定NRG1的相對(duì)表達(dá)量。結(jié)果：1、25只大鼠糖尿病造模成功24只,造模成功率為96%(24/25),其中有1只在注射藥物后第二天死亡,死亡率為4%(1/25)考慮STZ中毒死亡所致。2、49只大鼠行自體頸外靜脈移植至頸總動(dòng)脈模型,建模成功45例,成功率為91.84%(45/49),其中DM組22例,NC組23例；其死亡率8.16%(4/49)。3、大鼠自體頸外靜脈移植術(shù)前糖尿病組靜脈橋壁內(nèi)膜厚度與對(duì)照組相比(4.54±0.39μm vs 4.59±0.6μm,P0.05),沒有統(tǒng)計(jì)學(xué)差異；而術(shù)后2周(50.68±2.34μm vs 45.95±3.1μm, P0.05),有統(tǒng)計(jì)學(xué)差異；術(shù)后4W (80.86±8.72μm vs 60.7±6.31μm, P0.01),有統(tǒng)計(jì)學(xué)差異。4、DM組和NC組術(shù)前靜脈橋中平滑肌細(xì)胞PCNA幾乎無陽性表達(dá)。移植術(shù)后2周血管平滑肌細(xì)胞PCNA陽性表達(dá)明顯增多并達(dá)高峰,以內(nèi)、中膜為主,4周陽性率明顯降低,與對(duì)照組相比,在術(shù)后2周(51.99±5.23 vs 30.5±5.16, P0.01)差異有統(tǒng)計(jì)學(xué)意義,在4周(18.85±3.20 vs 15.14±1.69, P0.05)差異仍有統(tǒng)計(jì)學(xué)意義。5、NRG1主要在平滑肌細(xì)胞的細(xì)胞質(zhì)和細(xì)胞膜為主。術(shù)后陽性率表達(dá)有所下降,以DM比較顯著；與對(duì)照組相比,0周時(shí)(85.01±1.87 vs 84.64 ±1.09, P0.05)無統(tǒng)計(jì)學(xué)意義,術(shù)后2周(72.12±6.30 vs 28.58±1.94, P 0.05)以及到4周時(shí)(34.53±2.07 vs 7.89±1.37, P0.01)差異均有統(tǒng)計(jì)學(xué)意義；PCNA與NRG1陽性率經(jīng)相關(guān)性統(tǒng)計(jì)分析結(jié)果示：NC組相關(guān)系數(shù)r=-0.21,P=0.4030.05,負(fù)相關(guān)無統(tǒng)計(jì)學(xué)意義,DM組相關(guān)系數(shù)r=-0.59,P=0.0.010.05,負(fù)相關(guān)有統(tǒng)計(jì)學(xué)意義。結(jié)論：1、大鼠自體移植靜脈手術(shù)后早期開始出現(xiàn)新生內(nèi)膜,逐漸增厚,主要是VSMC增殖、遷移所致2、自體靜脈移植術(shù)后同一時(shí)間點(diǎn),與對(duì)照組相比,糖尿病內(nèi)膜增厚明顯；3、自體靜脈移植術(shù)后,NRG1表達(dá)下調(diào)顯著以致PCNA高表達(dá),可能是糖尿病組VSMC增殖、內(nèi)膜增厚明顯的關(guān)鍵因素之一；4、NRG1可能成為糖尿病再狹窄治療的新的靶點(diǎn)。
[Abstract]:Background and purpose: the study found that at least 65% patients with diabetes (DM) died of coronary arteriosclerotic heart disease. Coronary artery bypass grafting (CABG) is an important means for the treatment of severe end-stage coronary lesions. Although multiple arterial graft has been applied to CABG successively, it is clinically used because of its lack of origin. So far the great saphenous vein is still the most commonly used vascular bridge. The long term myocardial infarction and mortality after the use of the great saphenous vein bridge for CABG combined with diabetes has significantly increased the cause and mechanism of intimal hyperplasia after.DM bridge, and there is no ideal method for prevention and treatment. It shows that the expression of NRG-1 in diabetic cardiovascular disease is obviously down-regulated, and NRG-1 can protect vascular endothelial cells and inhibit the proliferation of smooth muscle, migration, and reduce oxidative stress. Therefore, it is necessary to explore whether NRG-1 is involved in the process of DM vein bridge restenosis. This study aims to establish a DM vein bridge model and explore the vein bridge in DM. The intimal thickening and NRG-1 expression changes in the environment are expected to provide a new way for the prevention and treatment of restenosis of vascular bridges in DM patients. 1, 50 rats were randomly selected for 8-10 weeks male (Sprague-Dawley rats) SD rats and weighed 200-220g, and were randomly divided into two groups: diabetes group (DM group, n=25) and normal group. The control group (group NC, n=25), group DM was given a large dose of STZ (55mg/kg) intraperitoneally to establish the diabetic rat model, and the NC group was given.2 in the diabetic rat model group with equal volume of normal saline injected with the tail vein of.3 after.3 days, and the DM rats (DM group) and normal rats (NC group) were randomly divided into 3 groups. 0 weeks (DM-OW, 2 weeks (DM-2W, n=6), 4 weeks (DM-4W, n=6) and normal group 0 weeks (NC-OW, n=6), 2 weeks (NC-2W, n=6), 4 weeks (NC-4W, n=6), after 1 weeks of injection, all rats were established by modified jugular vein graft common carotid artery model, and two groups of 0 weeks, 2 weeks, 4 weeks of vascular bridge examination, respectively, to measure two group of blood. The thickness of the tube wall and the difference in the thickness of the middle membrane were compared with those of the two. The expression of PCNA and NRG1 was detected by immunohistochemistry and the relative expression of NRG1 was measured by Western blot. Results: 24 rats were successfully established with diabetes, and the success rate of the model was 96% (24/25), of which 1 were killed second days after the injection and the mortality rate was 4% (1/25). The model of autologous external jugular vein graft to common carotid artery was considered in.2,49 rats with STZ poisoning death. 45 cases were successfully modeled, the success rate was 91.84% (45/49), including 22 cases in group DM and 23 in NC group; the mortality rate was 8.16% (4/49).3, and the intima thickness of vein bridge wall in the diabetic group was compared with the control group (4.54 + 0.39, m vs 4). .59 + 0.6 m, P0.05), without statistical difference, but 2 weeks after operation (50.68 + 2.34 Mu vs 45.95 + 3.1 m, P0.05), there were statistical differences; 4W (80.86 + 8.72 micron vs 60.7 + 6.31 mu m, P0.01) was statistically different after operation. The positive expression of CNA was significantly increased and reached its peak. The positive rate of the middle membrane was less than that of the control group. Compared with the control group, the difference was statistically significant at the 2 week (51.99 + 5.23 vs 30.5 + 5.16, P0.01) after the operation. The difference was still statistically significant at 4 weeks (18.85 + 3.20 vs 15.14 +, P0.05), and NRG1 mainly in the cytoplasm and cell of smooth muscle cells. The expression of membrane was dominant. The expression of positive rate decreased after operation. Compared with the control group, there was no statistical significance at 0 weeks (85.01 + 1.87 vs 84.64 + 1.09, P0.05), 2 weeks after operation (72.12 + 6.30 vs 28.58 + 1.94, P 0.05) and 1.87 weeks (34.53 + vs, P0.01) differences were statistically significant; PCNA and NRG1 positive rates were in phase The correlation coefficient of the NC group was r=-0.21, P=0.4030.05, and the negative correlation was not statistically significant. The correlation coefficient of group DM was r=-0.59, P=0.0.010.05, and the negative correlation was statistically significant. Conclusion: 1, the neointima began to appear in the early stage of autologous vein transplantation in rats, gradually thickening, mainly the proliferation of VSMC, the migration of 2, autogenous vein migration. At the same time after implantation, the thickening of the intima of diabetes was obvious compared with the control group. 3, after autologous vein transplantation, the expression of NRG1 was significantly reduced so that the high expression of PCNA could be one of the key factors for the proliferation of VSMC in the diabetic group and the thickening of the intima, and 4, NRG1 may be a new target for the treatment of diabetes restenosis.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R587.1

【參考文獻(xiàn)】

相關(guān)期刊論文 前4條

1 胡召云;陳武;;四肢血管損傷的顯微外科治療[J];安徽醫(yī)藥;2008年09期

2 劉蘇健;鄧勇志;馬捷;;大鼠血管移植模型的建立及改進(jìn)[J];山西醫(yī)科大學(xué)學(xué)報(bào);2007年10期

3 李艷波,鄧華聰,鄭丹,李呼倫;P38信號(hào)通路對(duì)人臍靜脈內(nèi)皮細(xì)胞單核細(xì)胞趨化蛋白-1表達(dá)的影響[J];中華糖尿病雜志;2004年04期

4 王日勝,霍勇;血管成形術(shù)后血管壁細(xì)胞表型的改變與再狹窄[J];中國(guó)介入心臟病學(xué)雜志;2000年02期

，

本文編號(hào)：2007608