8-羟基脱氧鸟苷与肾间质纤维化的相关性研究
发布时间：2018-09-18 13:51
【摘要】：目的:分析8-羟基脱氧鸟苷(8-hydroxy-2'-deoxyguanosine,8-OHdG)与肾间质纤维化(renal interstitial fibrosis,RIF)进展的相关性,初步探讨氧化应激(oxidative stress,OS)在UUO大鼠RIF发生、发展过程中的可能作用。方法:将48只雄性SD大鼠随机分为UUO模型组(UUO组)和Sham假手术组(Sham组),每组24只。在术后3、7、14、21天时各组分别处死6只,收集血清、24小时尿及肾组织标本。测定血尿素(BUN)、血肌酐(Scr);苏木精/伊红(hematoxylin/eosin,HE)、Masson染色观察肾脏病理改变、酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)法检测血清、尿液8-OHdG、转化生长因子-β1(transforming growth factor-beta 1,TGF-β1),分光光度法检测血清总过氧化物歧化酶(total-superoxide dismutase,T-SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GPx)及丙二醛(malondialdehyde,MDA)。结果:(1)与Sham组比较,UUO组大鼠肾小管间质损害明显并随病程延长进行性加重,呈急性肾小管损伤至间质纤维化的典型UUO模型表现。(2)与Sham组比较,UUO组在造模后3天、7天、14天、21天时的左肾重量、血尿素、肌酐均明显升高(P㩳0.05)。(3)纤维化指标变化:与Sham组比较,UUO组造模后各时间点的血清TGF-β1均显著高于Sham组(P㩳0.05)(4)氧化应激指标变化:UUO组在造模后7天时的血T-SOD高于Sham组(P㩳0.05),而在造模后3天、14天、21天时两组间无明显差异;与造模后3天,7天时比较、14天、21天时UUO组血清GPx水平进行性下降,差异有统计学意义(P㩳0.01);。UUO组在造模后21天时的血、尿8-OHdG明显高于Sham组(P㩳0.01),其他时间点两组间的差异无统计学意义;血清MDA、T-SOD及尿液8-0HdG在各时间点间无明显差异。(5)相关分析显示:血清8-OHdG与血清TGF-β1(r=0.485,P=0.016)及血MDA(r=0.419,P=0.042)呈正相关,与肾间质纤维化评分(r=-0.503,P=0.012)呈负相关。结论:1、氧化应激可能通过影响TGF-β1的水平参与了UUO大鼠肾间质纤维化的进展过程。2、血8-OHdG作为氧化应激过程中DNA氧化损伤的主要代谢产物与UUO大鼠肾间质纤维化的进展存在一定的相关性。
[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.
【学位授予单位】：宁夏医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692
[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.
【学位授予单位】：宁夏医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692
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