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目的观察甘草酸二胺联合前列地尔对大鼠肾间质纤维化的影响。方法建立单侧输尿管梗阻(UUO)动物模型,将120只大鼠随机分为假手术组、模型组、甘草酸二胺组、前列地尔组、甘草酸二胺加前列地尔组,每组24只。术后第7、14、21天每组各处死8只大鼠,测定其血清肌酐(CREA)水平,HE染色后观察肾间质变化,免疫组化法观察肾间质转化生长因子-β1(TGF-β1)和结缔组织生长因子(CTGF)的表达,酶联法测定血清TGF-β1、CTGF浓度。结果模型组在术后第14、21天时血清CREA、TGF-β1、CTGF浓度及TGF-β1、CTGF在肾组织的表达较假手术组均显著增加(P均<0.01);甘草酸二胺加前列地尔组的肾间质损伤指数及TGF-β1、CTGF在肾间质的表达和血清中TGF-β1、CTGF的浓度均明显低于其他治疗组(P均<0.01)。结论甘草酸二胺联合前列地尔能改善UUO所致的肾间质纤维化,其机制可能与下调肾组织的TGF-β1、CTGF表达有关。
Objective To observe the effect of glycyrrhizic acid diamine combined with alprostadil on renal interstitial fibrosis in rats. Methods The unilateral ureteral obstruction (UUO) animal models were established. 120 rats were randomly divided into sham operation group, model group, glycyrrhizic acid diamine group, alprostadil group, glycyrrhizin plus alprostadil group, 24 only. Eight rats were sacrificed on the 7th, 14th and 21st day after operation, respectively. Serum creatinine (CREA) levels were measured. The changes of renal interstitium were observed after HE staining. The expression of transforming growth factor-β1 TGF-β1) and connective tissue growth factor (CTGF) were detected by ELISA. Serum TGF-β1 and CTGF concentrations were measured by ELISA. Results The expression of CREA, TGF-β1 and CTGF and the expression of TGF-β1 and CTGF in renal tissue in model group were significantly higher than those in sham-operation group on the 14th and 21st day after operation (all P <0.01) Proliferation of renal interstitium and the expression of TGF-β1 and CTGF in renal interstitium and the concentrations of serum TGF-β1 and CTGF in the alprostadil group were significantly lower than those in other groups (all P <0.01). Conclusion Glycyrrhizin combined with alprostadil can improve renal interstitial fibrosis induced by UUO, which may be related to down-regulation of TGF-β1 and CTGF expression in renal tissue.