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目的:探讨丹参酚酸B(SA-B)对肾间质纤维化大鼠的作用及机制。方法:36只雄性SD大鼠随机分为假手术组、模型组和SA-B治疗组。单侧输尿管结扎术(UUO)建立肾间质纤维化模型。造模的同时SA-B治疗组灌喂SA-B水溶液(12.5mg/kg)。第14、21天处死大鼠,观察肾功能的变化,HE和PASM染色光镜下观察肾组织的病理变化,用盐酸水解法检测肾组织中羟脯氨酸的含量,Westernblot法检测肾组织基质金属蛋白酶-2(MMP-2)和基质金属蛋白抑制剂-2(TIMP-2)蛋白表达,明胶酶谱观察MMP-2活性。结果:与假手术组比较,模型组大鼠血肌酐、尿素氮和羟脯氨酸的含量均有明显上升;肾小球正常,肾间质增宽,间质内有大量的炎性细胞和间质细胞出现,肾小管扩张较明显,后期可见到部分肾小管萎缩,肾小管的基底膜明显增厚;肾组织的MMP-2蛋白、活性和TIMP-2蛋白水平均高于同期假手术组。SA-B干预后,血肌酐、尿素氮和羟脯氨酸的含量明显降低;上述病理改变明显轻于模型组,肾组织的MMP-2蛋白、活性水平和TIMP-2蛋白表达明显减少。结论:SA-B可抑制肾组织MMP-2和TIMP-2的蛋白表达,从而改善UUO大鼠的肾间质纤维化和肾功能。
Objective: To investigate the effect and mechanism of salvianolic acid B (SA-B) on renal interstitial fibrosis in rats. Methods: Thirty-six male SD rats were randomly divided into sham operation group, model group and SA-B treatment group. Unilateral ureteral ligation (UUO) model of renal interstitial fibrosis. At the same time as modeling, SA-B treatment group was fed SA-B solution (12.5mg / kg). The rats were sacrificed on the 14th and 21st day to observe the changes of renal function. The pathological changes of renal tissues were observed under light microscope with HE and PASM staining. The contents of hydroxyproline in renal tissues were detected by hydrochloric acid hydrolysis method. The expressions of MMP-2 and TIMP-2 were detected by enzyme-linked immunosorbent assay (ELISA). The activity of MMP-2 was detected by gelatin zymography. Results: Compared with the sham operation group, the levels of serum creatinine, urea nitrogen and hydroxyproline in model group were significantly increased; glomerular normal, broadening renal interstitium, a large number of inflammatory cells in the interstitium and Interstitial cells appeared, tubule dilatation is more obvious, the late part of the renal tubules can be seen atrophy, tubulointerstitial thickening; renal tissue MMP-2 protein, TIMP-2 protein and activity were higher than the same period sham operation group . The levels of serum creatinine, urea nitrogen and hydroxyproline in SA-B group were significantly lower than those in model group. The expression of MMP-2 protein, TIMP-2 protein and TIMP-2 protein in renal tissue were significantly decreased. Conclusions: SA-B can inhibit the protein expression of MMP-2 and TIMP-2 in renal tissue and thus improve renal interstitial fibrosis and renal function in UUO rats.