【摘要】 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。更多还原

【Abstract】 Objective:To investigate the effect of salvianolic acid B(SA-B)on renal interstitial fibrosis in rats and its mechanisms.Methods:Thirty six male sprague-dawley rats were randomly divided into sham group,model group and SA-B treatment group.Rat models of renal interstitial fibrosis were established with unilateral ureteral ligation(UUO)Meanwhile,the rats in SA-B treatment group were treated with SA-B at a dose of 1.25 mg/kg daily.After 14 and 21 days of UUO,6 rats in each group were sacrificed respectively and the obstructed kidney were collected for HE staining and methenamine silver(PASM)stain to check the histological changes of renal interstitial tissues.Hydroxyproline(Hyp)content of kidney was assayed with jamall’s method.The protein expressions of MMP-2 and TIMP-2 in renal tissues were detected with Western blot,and the activities of MMP-2 were detected by gelatin zymography.Results:Serum creatinine(Scr),blood urea nitrogen(BUN)and Hyp in the model group were significantly higher than those in the sham group.Moreover,in the model group,tubules lumen were widened and the basement membranes were thickened than that in sham group.There was no significant difference in glomerular damage between the the model group and sham group.Many inflammatory cells infiltrated in the renal interstitium parallels the extent of fibrogenesis.The tubular epithelial cells were karyorrhexis or karyolysis,some tubulars were atrophy.The protein expression and activity of MMP-2 and protein expression of TIMP-2 in kidney tissue were significantly up-regulated in the model group.After intervention with SA-B,the renal pathological status in the treatment group was significantly alleviated,the expression and activity of MMP-2 were significantly down-regulated,and the level of TIMP-2 in renal tissues decreased significantly.Conclusion:SA-B can alleviate renal interstitial fibrosis and improve the renal function by inhibiting MMP-2 and TIMP-2 expressions in UUO rats.更多还原