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目的探讨亚硒酸钠对单侧输尿管梗阻(UUO)模型大鼠肾间质纤维化的作用及其对肾间质转化生长因子-β1(TGF-β1)表达及氧化应激指标变化的影响。方法以单侧输尿管结扎建立肾间质纤维化大鼠模型。将90只SD大鼠随机分为假手术组(A组)、UUO组(B组)、UUO+硒组(C组)、UUO+硒及维生素E组(D组)、UUO+贝那普利组(E组),每组18只。C、D、E组分别给予亚硒酸钠(0.2mg.kg-1.d-1)、亚硒酸钠(0.2mg.kg-1.d-1)+维生素E(200mg.kg-1.d-1)和贝那普利(10mg.kg-1.d-1)灌胃。A、B组给予同等剂量生理盐水灌胃。术后第7、14、21天各组随机处死6只大鼠,肾组织行HE、Masson染色评定各组肾间质纤维化程度,免疫组织化学半定量法检测各组肾间质TGF-β1的表达。化学比色法检测肾组织匀浆中氧化指标谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、丙二醛(MDA)的含量。结果手术后第7、14、21天,C组肾间质纤维化程度较B组明显减轻(P<0.05),肾组织TGF-β1的表达强度明显低于B组(P<0.01或P<0.05),GSH-Px和SOD含量明显高于B组(P<0.05),MDA含量明显低于B组(P<0.05);而上述各项指标与D组和E组比较差异无统计学意义(P>0.05)。结论硒可能通过减轻肾组织氧化应激反应,下调TGF-β1表达,延缓肾间质纤维化,从而起到肾脏保护作用。
Objective To investigate the effect of sodium selenite on renal interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) and its effect on the expression of transforming growth factor-β1 (TGF-β1) and oxidative stress. Methods A rat model of renal interstitial fibrosis was established by unilateral ureteral ligation. Ninety Sprague-Dawley rats were randomly divided into three groups: sham operation group (group A), UUO group (group B), UUO + selenium group (group C), UUO + selenium and vitamin E group Group E), 18 in each group. Sodium selenite (0.2mg.kg-1.d-1), sodium selenite (0.2mg.kg-1.d-1) + vitamin E (200mg.kg-1 .d-1) and benazepril (10 mg.kg-1.d-1). A, B group given the same dose of normal saline gavage. Six rats were randomly sacrificed on the 7th, 14th and 21st day after operation. The renal interstitial fibrosis was evaluated by HE and Masson staining. The expression of TGF-β1 in renal interstitium was detected by immunohistochemical semiquantitative analysis expression. The contents of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) in kidney homogenate were detected by chemical colorimetry. Results On the 7th, 14th and 21st day after operation, the degree of renal interstitial fibrosis in group C was significantly lower than that in group B (P <0.05), while the expression of TGF-β1 in renal tissue was significantly lower than that in group B (P <0.01 or P < 0.05). The contents of GSH-Px and SOD were significantly higher than those in group B (P <0.05) and the content of MDA was significantly lower than that in group B (P <0.05). There was no significant difference between the above indexes and D and E groups (P> 0.05). Conclusion Selenium may protect the kidneys by reducing oxidative stress in renal tissues, down-regulating the expression of TGF-β1, and retarding renal interstitial fibrosis.