本文選題：DNA雙鏈損傷修復(fù)機制 + 細胞衰老��； 參考：《四川大學(xué)學(xué)報(醫(yī)學(xué)版)》2017年02期

【摘要】：目的探討DNA雙鏈損傷修復(fù)機制在糖尿病致動脈粥樣硬化中的作用。方法將Wistar雄性大鼠隨機分為3組,即正常對照組(A組),主動脈內(nèi)膜球囊損傷組(B組),糖尿病模型+主動脈內(nèi)膜球囊損傷組(C組)。C組采用鏈脲霉素(STZ)一次性腹腔注射建立糖尿病模型,注射STZ 72h后,B組與C組大鼠均被施行主動脈球囊損傷術(shù),術(shù)后分別予以高脂飼料飼養(yǎng);A組予以基礎(chǔ)飼養(yǎng),每周監(jiān)測血糖水平及體質(zhì)量變化。分別于術(shù)后2周、4周、6周、8周,取大鼠主動脈進行老化β-半乳糖苷酶(SA-β-gal)染色、HE染色,并計算主動脈內(nèi)膜面積、中膜面積、內(nèi)中膜面積比,免疫組織化學(xué)染色檢測磷酸化共濟失調(diào)毛細血管擴張突變基因(ATM)、磷酸化細胞周期檢測點激酶2(CHK2)、磷酸化P53、磷酸化組蛋白2A變異體(γ-H2AX)的表達。結(jié)果術(shù)后2周,A組大鼠主動脈內(nèi)膜老化SA-β-gal染色呈陰性,B組和C組大鼠老化SA-β-gal染色陽性區(qū)域較少且散在分布;HE染色示B組和C組大鼠主動脈內(nèi)膜開始出現(xiàn)少量增生。術(shù)后4周,B組和C組大鼠主動脈內(nèi)膜老化SA-β-gal染色呈陽性;HE染色示C組大鼠主動脈內(nèi)膜增厚明顯,主動脈內(nèi)膜面積較A組和B組增加(P0.05)。術(shù)后6周,C組大鼠主動脈內(nèi)膜老化SA-β-gal染色呈陽性且面積較B組增加;HE染色示C組大鼠主動脈壁形成典型動脈粥樣硬化斑塊,斑塊內(nèi)平滑肌細胞排列紊亂,泡沫細胞聚集,管腔狹窄,與A組、B組相比,主動脈內(nèi)中膜面積比增加(P0.05)。術(shù)后8周,C組大鼠主動脈內(nèi)膜老化染色陽性面積較B組增加;HE染色示C組大鼠主動脈腔明顯狹窄,增生部分突入管腔,內(nèi)膜面積、內(nèi)中膜面積比較A組和B組增加(P0.05);免疫組化染色示C組大鼠主動脈內(nèi)膜中γ-H2AX、磷酸化ATM、磷酸化CHK2、磷酸化P53表達均呈陽性,上述蛋白在B組大鼠主動脈內(nèi)膜中表達均呈弱陽性。結(jié)論糖尿病狀態(tài)下,血管內(nèi)皮細胞衰老激活,DNA雙鏈損傷加劇,雙鏈損傷修復(fù)機制參與了糖尿病致動脈粥樣硬化的發(fā)生發(fā)展。
[Abstract]:Objective to investigate the role of DNA double strand damage repair mechanism in atherosclerosis induced by diabetes mellitus. Methods Wistar male rats were randomly divided into three groups. The diabetic model was established by intraperitoneal injection of streptozotocin (STZ) by intraperitoneal injection of streptozotocin (STZ) in normal control group, aortic intima balloon injury group (group B) and diabetic model aortic intima balloon injury group (group C). 72 hours after STZ injection, the rats in group B and group C were treated with balloon injury of aorta. The rats in group A were fed with high fat diet respectively. The blood glucose level and body mass were monitored weekly. The aorta of the rat was harvested for aging 尾 -galactosidase SA- 尾 -gal) staining at 2 weeks, 4 weeks, 6 weeks and 8 weeks, respectively. The area of intima, the area of middle membrane and the ratio of area of medial membrane of aorta were calculated. Immunohistochemical staining was used to detect the expression of phosphorylated ataxia telangiectasia mutant gene, phosphorylated cell cycle detection point kinase 2, phosphorylated p53, and phosphorylated histone 2A variant (緯 -H2AX). Results two weeks after operation, SA- 尾 -gal staining was negative in group A and group C, and there were few SA- 尾 -gal staining positive areas in group B and C, and scattered HE staining showed that a small number of hyperplasia of aortic intima began to appear in group B and group C. 4 weeks after operation, SA- 尾 -gal staining showed that the aortic intima of group C was thicker than that of group A and group C, and the area of aortic intima was increased by P0.05a than that of group A and B by SA- 尾 -gal staining. At 6 weeks after operation, SA- 尾 -gal staining of aortic intima aging in group C was positive and its area was larger than that in group B. He staining showed that typical atherosclerotic plaques were formed in aortic wall of rats in group C, smooth muscle cells in plaques were disordered and foam cells were accumulated. Compared with group A and B, the ratio of medial area of aorta to lumen stenosis was increased (P 0.05). At 8 weeks after operation, the positive area of aging staining of aortic intima in group C was increased compared with that in group B. The results of HE staining showed that the aortic lumen in group C was obviously narrow, and the proliferative part protruded into the lumen of aorta, and the area of intima was increased. Immunohistochemical staining showed that the expression of 緯 -H2AX, phosphorylated ATM, phosphorylated CHK2 and phosphorylated p53 in aortic intima of group C were all positive, and the expression of these proteins was weakly positive in the intima of aorta of group B. Conclusion under the condition of diabetes, the aging activated DNA double strand damage of vascular endothelial cells is aggravated, and the repair mechanism of double strand damage is involved in the occurrence and development of diabetes induced atherosclerosis.
【作者單位】： 四川大學(xué)華西醫(yī)院老年科;四川省醫(yī)學(xué)科學(xué)院·四川省人民醫(yī)院干部科;成都軍區(qū)總醫(yī)院老年科;南充市中心醫(yī)院老年科;
【分類號】：R587.2;R543.5

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