本文關鍵詞： 自體動靜脈內瘺 內膜增生 血管內皮生長因子-A 單核細胞趨化蛋白-1 受激活調節(jié)正常T細胞表達和分泌　出處：《河北醫(yī)科大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:自體動靜脈內瘺(arteriovenous fistula,AVF)是血液透析患者首選的血管通路。但是AVF失功率較高。近吻合口靜脈內膜增生,導致血管狹窄是AVF失功的最主要原因,在組織學上表現為血管平滑肌細胞的遷移和增殖,新生血管形成以及細胞外基質的過度沉積。盡管確切發(fā)病機制尚未清楚,但是實驗和臨床研究發(fā)現,多種細胞因子參與這一過程。血管內皮生長因子-A(Vascular endothelial growth factor-A,VEGF-A)可以促進內皮細胞和平滑肌細胞的增殖、遷移,同時能夠促進單核細胞、巨噬細胞聚集。尤其是在血管重塑和再狹窄中發(fā)揮重要作用。炎癥在AVF狹窄中起到重要作用,而單核細胞趨化蛋白-1(Monocyte chemoattractant protein-1,MCP-1)可以促進單核、巨噬細胞浸潤到炎癥部位。還能夠活化并且促進平滑肌細胞向內膜的遷移與增殖,此外,它還可調節(jié)血管生成,并且在血管重塑和炎癥性疾病中起到重要作用。受激活調節(jié)正常T細胞表達和分泌因子(Regulated upon activation,normal T-cell expressed and secreted,RANTES)作為一種趨化因子可以活化炎癥細胞,并趨化炎癥細胞向損傷和炎癥部位聚集。尤其在促進血管生成中起到非常重要作用。本實驗通過檢測AVF靜脈標本中VEGF-A、MCP-1和RANTES表達水平的變化,探討VEGF-A、MCP-1以及RANTES與AVF內膜增生的關系。方法:選取28名已行規(guī)律血液透析治療的終末期腎臟病患者,分為實驗組和對照組。其中實驗組14名為因近吻合口靜脈狹窄導致AVF失功來我科行AVF重建術的患者。對照組則為擬初次行AVF成形術的14名患者。實驗組患者行AVF重建術時,切取廢棄的完整增生肥厚的靜脈組織約1cm作為實驗組;對照組患者初次行AVF端側吻合術,將頭靜脈結扎切斷后,于近心端切取0.5-1cm的完整靜脈作為對照組。各組標本分別進行HE和免疫組織化學染色,并于光鏡下觀察。所得實驗數據均采用SPSS 21.0統(tǒng)計軟件進行分析,結果用均數±標準差(x±s)表示,p0.05認為差異具有統(tǒng)計學意義。結果:1患者臨床基本統(tǒng)計學資料對2組患者年齡、性別及腎衰竭原發(fā)病構成比進行統(tǒng)計學分析,差異均無統(tǒng)計學意義(p0.1)。2 HE染色光鏡下觀察發(fā)現實驗組失功AVF的靜脈內膜明顯增厚,并有大量炎細胞浸潤和新生血管形成,對照組靜脈內膜未見明顯增生肥厚,無明顯炎細胞浸潤及新生血管形成,對實驗組和對照組的內膜/中膜厚度比和內膜/中膜面積比進行了比較,差異具有統(tǒng)計學意義(p均0.001)。3免疫組織化學染色3.1 VEGF-A免疫組織化學染色VEGF-A表達主要位于胞漿中。在實驗組中以強陽性表達為主,主要位于中膜和內膜;而對照組靜脈VEGF-A表達呈弱陽性,主要位于內膜和中膜,其中內膜較明顯。實驗組VEGF-A的表達水平明顯高于對照組,差異具有統(tǒng)計學意義(p0.01)。3.2 MCP-1免疫組織化學染色MCP-1主要表達于胞漿中。實驗組以強陽性表達為主,位于靜脈內膜和中膜。而對照組MCP-1表達以弱陽性為主,位于靜脈內膜和中膜,以中膜更明顯。實驗組MCP-1的表達水平明顯高于對照組,差異具有統(tǒng)計學意義(p0.01)。3.3 RANTES免疫組化染色RANTES主要表達于胞漿。實驗組RANTES表達以強陽性為主,主要在內膜和中膜。對照組RANTES呈弱陽性表達,位于內膜和中膜。實驗組RANTES的表達水平明顯高于對照組,差異具有統(tǒng)計學意義(p0.01)。3.4免疫組織化學染色的陰性對照:陰性對照組內膜和中膜均未見陽性染色,血管外膜呈棕黃色,但是未見陽性細胞,考慮為非特異性染色。結論:1 VEGF-A、MCP-1及RANTES的高表達與靜脈內膜增生密切相關,可能成為未來干預的靶點。2 VEGF-A可能通過介導MCP-1的表達,繼而介導RANTES的表達,在AVF內膜增生中發(fā)揮作用。3 VEGF-A也可能直接介導MCP-1和RANTES的表達,在AVF內膜增生中發(fā)揮作用。
[Abstract]:Objective: autologous arteriovenous fistula (arteriovenous fistula AVF) is the preferred vascular access in hemodialysis patients. But the AVF loss of high power. Nearly kiss intimal hyperplasia stoma, lead to vascular stenosis is the main cause of AVF dysfunction, in histologically vascular smooth muscle cell migration and proliferation, angiogenesis and excessive deposition of extracellular matrix. Although the exact pathogenesis is not clear, but the experimental and clinical study found that many cytokines involved in this process. Vascular endothelial growth factor -A (Vascular endothelial growth factor-A, VEGF-A) can promote endothelial cell and smooth muscle cell proliferation, migration, and can promote monocyte macrophage accumulation. Especially play an important role in vascular remodeling and restenosis. Inflammation plays an important role in AVF stenosis, and monocyte chemoattractant protein -1 (Monocyte Ch Emoattractant protein-1, MCP-1) can promote monocyte, macrophage infiltration into inflammatory sites. Also can activate and promote smooth muscle cell migration and proliferation of the endometrium, in addition, it can also regulate angiogenesis, and play an important role in vascular remodeling and inflammatory diseases. Regulated upon activation normal T cell expressed and secreted (Regulated upon activation, normal T-cell expressed and secreted, RANTES) is a chemokine activation of inflammatory cells, and chemotactic aggregation of inflammatory cells to injury and inflammation in the body. Especially in the promotion play an important role in angiogenesis. The detection of AVF MCP-1 and VEGF-A in venous samples, the change of the expression of RANTES to investigate, VEGF-A, MCP-1 and AVF between RANTES and endometrial hyperplasia. Methods: 28 patients who underwent hemodialysis treatment in patients with end-stage renal disease, divided into The experimental group and control group. The experimental group was 14 for anastomotic vein stenosis resulting in AVF loss to our department for reconstruction of AVF patients. The control group was intended to initial AVF plasty in 14 patients. The experimental group underwent AVF reconstruction, vein cut complete hypertrophy from waste about the 1cm as the experimental group; the control group of patients undergoing primary AVF end to side anastomosis, the cephalic vein ligation after complete venous 0.5-1cm cut as control group at the proximal end. All specimens were HE and immunohistochemical staining, and observed under light microscope. The experimental data were treated by SPSS 21 statistical software for analysis, the standard deviation (x + s) said, P0.05 considered statistically significant. Results: 1 patients with clinical basic demographic data of 2 groups of patients age, proportion for statistical analysis of gender and renal failure of primary disease, the differences were No statistical significance (P0.1) found that the experimental group loss AVF venous intima thickening obviously were observed under light microscope..2 HE staining, and a large number of inflammatory cell infiltration and neovascularization, the control group had no obvious intimal hypertrophy, no obvious inflammatory cell infiltration and neovascularization of the experimental group and control group endometrium / in the film thickness and the ratio of intima / media area ratio were compared, the difference was statistically significant (P 0.001).3 immunohistochemistry 3.1 VEGF-A immunohistochemical staining of VEGF-A expression was mainly located in the cytoplasm. With strong positive expression in the experimental group, mainly located in the membrane and the membrane; and the control group the expression of VEGF-A was weakly positive, mainly located in the intima and media, the endometrium is obvious. The expression level of VEGF-A in the experimental group was significantly higher than the control group, the difference was statistically significant (P0.01).3.2 MCP-1 immunohistochemistry MCP -1 was mainly expressed in the cytoplasm. The experimental group with strong positive expression mainly located in the intima and media of vein. While the control group with weak positive MCP-1 expression mainly located in venous intima and media, in the film is more obvious. The expression level of MCP-1 in the experimental group was significantly higher than the control group, the difference has statistical significance (P0.01.3.3 RANTES) immunohistochemical staining of RANTES was mainly expressed in the cytoplasm. RANTES expression in the experimental group with strong positive, mainly in the intima and the control group. The expression of RANTES was weakly positive, located in the intima and media. The expression level of RANTES in the experimental group was significantly higher than the control group, the difference was statistically significant (P0.01) immune.3.4 histochemical staining of the negative control: negative control group, intima and adventitia showed no positive staining was brown, but no positive staining cells, considered nonspecific. Conclusion: 1 VEGF-A, high expression of MCP-1 and RANTES and static Vein intimal hyperplasia is closely related to the expression, may become targets of.2 VEGF-A future intervention may be mediated by MCP-1, then the expression of RANTES mediated by.3 VEGF-A AVF, play a role in endometrial hyperplasia may also direct expression mediated by MCP-1 and RANTES, AVF play a role in neointimal hyperplasia.

【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】：2017
【分類號】：R459.5

【參考文獻】

相關期刊論文 前1條

1 Ehsan Rajabi-Jaghargh;Rupak K Banerjee;;Combined functional and anatomical diagnostic endpoints for assessing arteriovenous fistula dysfunction[J];World Journal of Nephrology;2015年01期

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本文編號：1442454