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厄贝沙坦对单侧输尿管梗阻大鼠肾间质纤维化的影响 被引量:3

Effect of Irbesartan on Renal Interstitial Fibrosis in Rats with Unilateral Ureteral Obstruction
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摘要 目的观察厄贝沙坦对单侧输尿管梗阻(UUO)大鼠肾间质纤维化的影响并探讨其可能机制。方法采用UUO肾间质纤维化模型。将24只大鼠随机分为3组,即假手术组、模型组、厄贝沙坦组,每组8只。厄贝沙坦组给予厄贝沙坦10 mg.kg-1.d-1。模型组与假手术组给予等量0.9%氯化钠溶液。术后2周处死大鼠,光镜下观察Masson和苏木精-伊红(HE)染色肾间质纤维化指数,观察肾组织病理改变,并应用免疫组织化学方法检测肾组织结缔组织生长因子(CTGF)和基质金属蛋白酶-2(MMP-2)的表达。结果与假手术组比较,模型组尿素氮(BUN)和血肌酐(Scr)水平均显著增加,厄贝沙坦组较模型组呈下降趋势。与假手术组比较,模型组肾组织行HE染色可见弥漫的肾小管上皮细胞空泡变性、扩张、部分萎缩,偶见坏死,肾间质增宽,大量的炎细胞浸润和间质纤维化,肾小球病理改变不明显,厄贝沙坦组上述改变均有所减轻。与假手术组比较,模型组Masson染色结果显示肾间质增宽、有大量胶原纤维增生,肾小球病变不明显,厄贝沙坦组上述改变均有所减轻。假手术组大鼠肾间质有少量CTGF表达,染色为颗粒状,着色稀疏;模型组CTGF表达明显增多,呈不均匀棕黄色颗粒状,肾小球表达不明显;厄贝沙坦组CTGF表达较模型组明显降低。MMP-2在假手术组大鼠肾间质中呈棕黄色颗粒状表达,模型组中大鼠肾间质仅有少量表达且着色稀疏,厄贝沙坦组MMP-2表达较假手术组减轻,但其表达仍高于模型组。结论厄贝沙坦可抑制CTGF的过度表达和增强MMP-2的表达,从而减缓肾纤维化的病程进展。 Objective To investigate the effects of irbesartan on renal interstitial fibrosis and its mechanism. Methods Renal interstitial fibrosis in rats was generated by unilateral ureteral obstruction (UUO). Adult female SD rats ( n = 24) were randomly divided into three groups : sham operation group (Sham) ; UUO group and irbesartan ( 10 mg·kg^-1·d^-1 ) group with UUO. The renal interstitial fibrosis index was observed under light microscopy by Masson and HE staining. The expression of CTGF and MMP-2 were tested by immunohistochemistry 2 weeks after surgery. Results The levels of BUN and Scr in UUO group were significantly higher than those in sham operated group, but lower in irbesartan group. It was shown that there were denatured tubular epithelial cells, expanding or partly atrophy, interstitial macrophage and monocyte infiltration, interstitial widening, without obvious glomeruli change in the UUO group. However, these pathological changes in irbesartan group were ameliorated. The Masson stainning on renal tissue showed that there was interstitial expanding, fibrous tissues proliferation and no glomeruli change in UUO group. Compared with UUO group, the level of pathological change in irbesartan group was significantly lower ( 43.05 ). The expression and distribution of CTGF was weak in sham operation group, while more obvious in other groups. Compared with UUO group, the level of CTGF in irbesartan group was significantly lower ( 43.05 ). The expression and distribution of MMP-2 was strong in sham group, while lower in other groups. Compared with UUO group, the level of MMP-2 in irbesartan group was significantly higher ( 43.05 ). Conclusion Irbesartan inhibits the over expression of CTGF and up-regulates MMP-2 expression, abating the development of renal interstitial fibrosis.
出处 《医药导报》 CAS 2009年第10期1258-1261,共4页 Herald of Medicine
关键词 厄贝沙坦 肾间质纤维化 输尿管梗阻 结缔组织生长因子 基质金属蛋白酶-2 Irbesartan Renal interstitlal fibrosis Unilateral ureteral obstruction CTGF MMP-2
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