论文部分内容阅读
目的研究肾康注射液对慢性马兜铃酸肾病(CAAN)模型大鼠肾间质纤维化的拮抗效应。方法雄性SD大鼠随机分为对照组、模型组和干预组,每组6只。于0、1、4、8、12周末分别检测体质量、尿糖2、4 h尿蛋白定量和肌酐清除率(Ccr);第12周末处死大鼠留取肾组织,行Masson染色观察肾间质纤维化程度;并用逆转录实时定量聚合酶链反应和免疫组织化学方法检测肾组织中转化生长因子-β1(TGF-β1)、结缔组织生长因子(CTGF)、纤溶酶原激活物抑制物-1(PAI-1)、金属蛋白酶组织抑制物-1(TIMP-1)和Ⅰ型胶原(Col I)mRNA及蛋白表达。结果与对照组比较,模型组和干预组大鼠体质量明显减轻(P<0.01),但干预组大鼠体质量明显高于模型组,12周末时存在显著差异(P<0.05)。与对照组相比,模型组大鼠24 h尿蛋白定量显著上升(P<0.01),Ccr显著下降(P<0.01);12周时肾间质纤维化面积显著增加(P<0.01);肾组织内上述各检测指标的mRNA及蛋白表达均显著上调(P<0.01)。与模型组相比,干预组大鼠各时间点Ccr均显著升高(P<0.01);第12周时24 h尿蛋白定量及肾间质纤维化面积均显著降低(P<0.05、0.01);上述高表达的mRNA及蛋白指标均被显著抑制(P<0.05)。结论肾康注射液可能通过抑制肾组织促细胞外基质(ECM)合成因子(TFG-β1、CTGF)及抗ECM降解因子(TIMP-1、PAI-1)生成,而改善CAAN的肾间质纤维化及肾功能。
Objective To study the antagonistic effect of Shenkang injection on renal interstitial fibrosis in rats with chronic aristolochic acid nephropathy (CAAN). Methods Male Sprague-Dawley rats were randomly divided into control group, model group and intervention group, with 6 rats in each group. At 0, 1, 4, 8 and 12 weekends, body mass, urinary urinary protein quantification, and creatinine clearance (Ccr) were measured. At the end of the 12th week, the rats were sacrificed and their kidney tissues were harvested. Masson staining was performed to observe the interrenal space. The extent of fibrosis; detection of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and plasminogen activator inhibitor in the kidney by RT-PCR and immunohistochemistry -1 (PAI-1), metalloproteinase tissue inhibitor-1 (TIMP-1) and type I collagen (Col I) mRNA and protein expression. Results Compared with the control group, the body weight of the model group and the intervention group was significantly reduced (P<0.01), but the body weight of the intervention group was significantly higher than that of the model group, and there was a significant difference at the end of the 12th week (P<0.05). Compared with the control group, the 24-hour urinary protein quantitation in the model group increased significantly (P<0.01), Ccr decreased significantly (P<0.01), and the renal interstitial fibrosis area increased significantly (P<0.01) at 12 weeks; The mRNA and protein expressions of the above-mentioned detection indicators in the tissues were significantly upregulated (P<0.01). Compared with the model group, the Ccr of the rats in the intervention group was significantly increased at each time point (P<0.01); at the 12th week, the 24-hour urinary protein and renal interstitial fibrosis area were significantly decreased (P<0.05, 0.01). The above highly expressed mRNA and protein indicators were significantly inhibited (P<0.05). Conclusion Shenkang injection may improve renal interstitial fibrosis of CAAN by inhibiting the production of extracellular matrix (ECM) synthesis factors (TFG-β1, CTGF) and anti-ECM degradation factors (TIMP-1, PAI-1). And renal function.