【摘要】：目的:分析8-羥基脫氧鳥苷(8-hydroxy-2'-deoxyguanosine,8-OHdG)與腎間質(zhì)纖維化(renal interstitial fibrosis,RIF)進展的相關(guān)性,初步探討氧化應(yīng)激(oxidative stress,OS)在UUO大鼠RIF發(fā)生、發(fā)展過程中的可能作用。方法:將48只雄性SD大鼠隨機分為UUO模型組(UUO組)和Sham假手術(shù)組(Sham組),每組24只。在術(shù)后3、7、14、21天時各組分別處死6只,收集血清、24小時尿及腎組織標本。測定血尿素(BUN)、血肌酐(Scr);蘇木精/伊紅(hematoxylin/eosin,HE)、Masson染色觀察腎臟病理改變、酶聯(lián)免疫吸附法(enzyme-linked immunosorbent assay,ELISA)法檢測血清、尿液8-OHdG、轉(zhuǎn)化生長因子-β1(transforming growth factor-beta 1,TGF-β1),分光光度法檢測血清總過氧化物歧化酶(total-superoxide dismutase,T-SOD)、谷胱甘肽過氧化物酶(glutathione peroxidase,GPx)及丙二醛(malondialdehyde,MDA)。結(jié)果:(1)與Sham組比較,UUO組大鼠腎小管間質(zhì)損害明顯并隨病程延長進行性加重,呈急性腎小管損傷至間質(zhì)纖維化的典型UUO模型表現(xiàn)。(2)與Sham組比較,UUO組在造模后3天、7天、14天、21天時的左腎重量、血尿素、肌酐均明顯升高(P㩳0.05)。(3)纖維化指標變化:與Sham組比較,UUO組造模后各時間點的血清TGF-β1均顯著高于Sham組(P㩳0.05)(4)氧化應(yīng)激指標變化:UUO組在造模后7天時的血T-SOD高于Sham組(P㩳0.05),而在造模后3天、14天、21天時兩組間無明顯差異;與造模后3天,7天時比較、14天、21天時UUO組血清GPx水平進行性下降,差異有統(tǒng)計學意義(P㩳0.01);。UUO組在造模后21天時的血、尿8-OHdG明顯高于Sham組(P㩳0.01),其他時間點兩組間的差異無統(tǒng)計學意義;血清MDA、T-SOD及尿液8-0HdG在各時間點間無明顯差異。(5)相關(guān)分析顯示:血清8-OHdG與血清TGF-β1(r=0.485,P=0.016)及血MDA(r=0.419,P=0.042)呈正相關(guān),與腎間質(zhì)纖維化評分(r=-0.503,P=0.012)呈負相關(guān)。結(jié)論:1、氧化應(yīng)激可能通過影響TGF-β1的水平參與了UUO大鼠腎間質(zhì)纖維化的進展過程。2、血8-OHdG作為氧化應(yīng)激過程中DNA氧化損傷的主要代謝產(chǎn)物與UUO大鼠腎間質(zhì)纖維化的進展存在一定的相關(guān)性。
[Abstract]:Aim: to investigate the relationship between 8-hydroxy-2-deoxyguanosine (8-OHdG) and the progression of renal interstitial fibrosis (renal interstitial fibrosis,RIF), and to explore the possible role of oxidative stress (oxidative stress,OS) in the pathogenesis and development of RIF in UUO rats. Methods: 48 male SD rats were randomly divided into UUO model group (UUO group) and Sham sham operation group (Sham group) with 24 rats in each group. Six rats were killed in each group on the 21st day after operation, and 24 hours urine and renal tissue specimens were collected. Blood urea (BUN), serum creatinine, (Scr); hematoxylin / eosin (hematoxylin/eosin,HE) were stained to observe the pathological changes of kidney and serum was detected by enzyme linked immunosorbent assay (enzyme-linked immunosorbent assay,ELISA). Urine 8-OHdG, transforming growth factor- 尾 1 (transforming growth factor-beta 1 (TGF- 尾 1), serum total peroxide dismutase (total-superoxide dismutase,T-SOD), glutathione peroxidase (glutathione peroxidase,GPx) and malondialdehyde (malondialdehyde,MDA) were detected by spectrophotometry. Results: (1) compared with the Sham group, the tubulointerstitial damage in UUO group was obvious and gradually aggravated with the prolongation of the course of disease. (2) compared with the Sham group, the left kidney weight and blood urea of the UUO group were compared with those of the Sham group on the 3rd day, 7th day, 14 day and 21 day after the model. Compared with Sham group, serum TGF- 尾 1 was significantly higher in UO group than that in Sham group (P0. 05). (4) the changes of oxidative stress index were higher than that of Sham group at 7 days after model making, but higher than that of Sham group at 7 days after model making, but the serum TGF- 尾 1 level was higher than that of Sham group at 7 days after model making in the control group (P < 0. 05), but the serum TGF- 尾 1 level in the control group was significantly higher than that in the control group (P < 0. 05). There was no significant difference between the two groups on the 3rd day, the 14th day and the 21st day after the model. The serum GPx level in the UUO group decreased progressively on the 14th day and 21st day after modeling compared with that on the 3rd and 7th day after modeling. The difference was statistically significant (P0. 01). The urinary 8-OHdG in the UUO group was significantly higher than that in the Sham group (P0. 01). There was no significant difference between the two groups at other time points. There was no significant difference between serum MDA,T-SOD and urine 8-0HdG at different time points. (5) the correlation analysis showed that serum 8-OHdG was positively correlated with serum TGF- 尾 1 (rn 0.485) and serum MDA (rn 0.419 P 0.042), but negatively correlated with renal interstitial fibrosis score (r-0.503P 0.012). Conclusion oxidative stress may be involved in the progression of renal interstitial fibrosis in UUO rats by affecting the level of TGF- 尾 _ 1. Blood 8-OHdG is the main metabolite of DNA oxidative damage in oxidative stress process and the progression of renal interstitial fibrosis in UUO rats. There is a certain correlation between the exhibition and the exhibition.
【學位授予單位】：寧夏醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R692

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