本文選題：IgA腎病 + 小鼠��； 參考：《遼寧醫(yī)學院》2012年碩士論文

【摘要】：目的 探討臍帶間充質(zhì)干細胞對IgA腎病小鼠模型尾靜脈注射后干細胞的歸巢及對腎小球系膜細胞的影響及其可能機制，，為干細胞移植在腎臟病治療領(lǐng)域中的應用提供新的途徑及理論依據(jù)。 方法 SPF級雄性昆明小鼠60只，按隨機數(shù)字法隨機分為對照組、模型組和人臍帶間充質(zhì)干細胞治療組（以下簡稱治療組）。利用牛血清白蛋白灌胃、皮下注射CCl4，應用脂多糖的復合方法造成小鼠IgA腎病模型。14周造模成功，尾靜脈注射人臍帶間充質(zhì)干細胞，于第7、21、56天處死小鼠取材，做免疫熒光染色證實造模成功，Masson染色觀察腎組織纖維化情況，免疫組化檢測VEGF、CTGF，免疫組化檢測CD44確定間充質(zhì)干細胞歸巢定位情況。Western Blot檢測VEGF、CTGF蛋白表達量，探討應用人臍帶間充質(zhì)干細胞治療IgA腎病的可能機制。 結(jié)果 造模成功后，模型組和治療組小鼠均出現(xiàn)蛋白尿，25只小鼠出現(xiàn)鏡下血尿，15只小鼠肉眼血尿，其中模型組13只小鼠出現(xiàn)鏡下血尿，7只小鼠出現(xiàn)肉眼血尿，治療組12只小鼠出現(xiàn)鏡下血尿，8只小鼠出現(xiàn)肉眼血尿；免疫熒光顯示IgA沉積于腎小球系膜區(qū)；干細胞治療后，MASSON染色顯示人間充質(zhì)干細胞治療組纖維化程度明顯較陰性對照組減輕，尿常規(guī)：24h蛋白尿治療組（7.15±0.31）、（4.87±0.22）、（2.95±0.16）g/24h，模型組（12.00±1.38）g/24h,均有P0.05。免疫組化檢測CD44觀察間充質(zhì)干細胞定位于腎小球及腎間質(zhì)內(nèi)，免疫組化定性觀察VEGF、CTGF在三組中分別有不同的陽性表達，Western Blot定量觀察VEGF、CTGF蛋白在三組中有不同的表達。 結(jié)論 在應用臍帶間充質(zhì)干細胞后，腎組織纖維化程度減輕，血尿蛋白尿減輕，IgA腎病癥狀明顯改善，提示人臍帶間充質(zhì)干細胞治療對IgA腎病小鼠模型具有保護作用。人臍帶間充質(zhì)干細胞注入IgA腎病小鼠模型后，可以通過趨化作用歸巢到腎組織內(nèi)，通過分泌細胞因子營造出適合微環(huán)境，使腎祖/干細胞重新分化為腎組織細胞，并通過調(diào)控VEGF、CTGF的表達水平來促使新生血管生成，減輕腎組織纖維化，修復受損腎小球系膜組織，使IgA腎病的一系列癥狀得到改善，從而達到治療IgA腎病的目的。
[Abstract]:Purpose To investigate the effect of umbilical cord mesenchymal stem cells on homing of stem cells and on glomerular Mesangial cells after caudal vein injection in mice with IgA nephropathy. To provide a new approach and theoretical basis for stem cell transplantation in the field of kidney disease treatment. Method Sixty male Kunming mice of SPF grade were randomly divided into control group, model group and human umbilical cord mesenchymal stem cell treatment group (hereinafter referred to as the treatment group). Bovine serum albumin (BSA) was perfused into the stomach and CCL4 was injected subcutaneously. The IgA nephropathy model of mice was established successfully by using lipopolysaccharide compound method. Human umbilical cord mesenchymal stem cells were injected into caudal vein, and the mice were killed on day 7, 21 and 56. The renal fibrosis was observed by Masson staining, the expression of VEGF CTGF was detected by immunohistochemistry, the homing location of mesenchymal stem cells was determined by immunohistochemistry, and the expression of VEGF CTGF protein was detected by Western Blot. To explore the possible mechanism of human umbilical cord mesenchymal stem cells in the treatment of IgA nephropathy. Result After the establishment of the model, the proteinuria was found in 25 mice in both the model group and the treatment group, and in 15 mice with hematuria under microscope, among them, 13 mice in the model group showed hematuria under microscope and 7 mice showed hematuria with naked eye. In the treatment group, 12 mice appeared hematuria under microscope, 8 mice showed naked hematuria, and IgA was deposited in glomerular Mesangial area by immunofluorescence. After the treatment of stem cells, the degree of fibrosis in the human mesenchymal stem cells group was significantly less than that in the negative control group. The urine routine 24 hours proteinuria group (7.15 鹵0.31) had 2.95 鹵0.16 g / 24 h, and the model group was 12.00 鹵1.38 g / r for 24 h, all with P0.05. CD44 was used to detect the location of mesenchymal stem cells (MSCs) in glomeruli and renal interstitium. The positive expression of VEGF CTGF in the three groups was observed qualitatively. Western Blot was used to quantitatively observe the different expression of VEGF CTGF protein in the three groups. Conclusion After the application of umbilical cord mesenchymal stem cells, the degree of renal fibrosis was alleviated, and the symptoms of IgA nephropathy were alleviated by hematuria proteinuria, suggesting that human umbilical cord mesenchymal stem cell therapy has protective effect on IgA nephropathy mice. After human umbilical cord mesenchymal stem cells were injected into IgA nephropathy mice model, they could homing into kidney tissue through chemotactic action, creating a suitable microenvironment by secreting cytokines, and redifferentiation of renal progenitor / stem cells into renal tissue cells. Through regulating the expression level of VEGF CTGF to promote neovascularization, alleviate renal fibrosis, repair the damaged glomerular Mesangial tissue, improve a series of symptoms of IgA nephropathy, so as to achieve the purpose of treating IgA nephropathy.
【學位授予單位】：遼寧醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R692.3;R-332

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