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目的探讨硒对肾间质纤维化大鼠肾组织结缔组织生长因子(CTGF)表达及肾小管上皮细胞表型转化的影响。方法以单侧输尿管结扎致肾间质纤维化大鼠模型。将54只SD大鼠随机分为假手术组(A组)、单侧输尿管梗阻(UUO)组(B组)、UUO+硒组(C组),每组18只。C组给予亚硒酸钠0.2mg/(kg·d)灌胃。A、B组给予同等剂量0.9%氯化钠溶液灌胃。术后第7、14、21天各组随机处死6只大鼠,肾组织行HE、Masson染色评定肾间质纤维化程度,免疫组织化学半定量法检测CTGF和α-平滑肌肌动蛋白(α-SMA)的表达。Western印迹法检测肾组织CTGF蛋白表达。化学比色法检测肾组织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)的表达水平。结果术后各时点C组肾间质纤维化程度较B组明显减轻(P<0.05),肾组织CTGF和α-SMA的表达强度明显低于B组(P<0.05或0.01)、GSH-Px和SOD水平明显高于B组(P<0.05),MDA含量明显低于B组(P<0.05)。B组肾组织中CTGF、a-SMA表达量之间呈正相关(P<0.05),CTGF和a-SMA表达量与肾间质纤维化病变程度呈正相关(P<0.05)。结论硒可以减轻UUO模型大鼠肾间质纤维化程度,其机制可能与硒的抗氧化作用、下调肾组织CTGF的表达、抑制肾小管上皮细胞-肌成纤维细胞转分化有关。
Objective To investigate the effect of selenium on the expression of connective tissue growth factor (CTGF) and the phenotype of renal tubular epithelial cells in rats with renal interstitial fibrosis. Methods Unilateral ureteral ligation of renal interstitial fibrosis rat model. 54 SD rats were randomly divided into sham operation group (group A), unilateral ureteral obstruction (group UUO) and group UUO + selenium (group C), 18 rats in each group. C group given sodium selenite 0.2mg / (kg · d) gavage. A, B group given the same dose of 0.9% sodium chloride solution gavage. Six rats were randomly sacrificed on the 7th, 14th and 21st day after operation. The renal tissues were examined for the degree of renal interstitial fibrosis by HE and Masson staining. The expressions of CTGF and α-SMA were measured by immunohistochemical semiquantitative analysis -SMA) expression. Western blotting was used to detect the expression of CTGF protein in renal tissue. The levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissue were detected by chemical colorimetry. Results The expression of CTGF and α-SMA in renal tissue was significantly lower in group C than in group B (P <0.05 or 0.01) The levels of Px and SOD were significantly higher than those in group B (P <0.05). The content of MDA in group B was significantly lower than that in group B (P <0.05). The expression of CTGF and a-SMA in group B was positively correlated (P <0.05). The expression of CTGF and a-SMA was positively correlated with the degree of renal interstitial fibrosis (P <0.05). Conclusion Selenium can reduce the degree of renal interstitial fibrosis in rats with UUO. The mechanism may be related to the anti-oxidation of selenium, the expression of CTGF in renal tissue, and the inhibition of renal tubular epithelial-myofibroblast transdifferentiation.