甲磺酸伊马替尼缓解小鼠肾组织纤维化作用研究

Administration of Imatinib Mesylate Attenuates Renal Fibrosis in Mice

目的研究甲磺酸伊马替尼(STI571)对单侧输尿管梗阻(UUO)小鼠肾间质纤维化的防治作用。方法40只雄性清洁级昆明种小鼠随机分为4组:假手术组、模型组、小剂量治疗组(80 mg.kg-1.d-1)、大剂量治疗组(160mg.kg-1.d-1)。治疗组在手术后分别以STI571 80,160 mg.kg-1.d-1灌胃。各组小鼠均于术后第8天处死。观察肾间质病理学改变;用酸水解-比色法测定肾组织胶原的含量,免疫组化技术检测α-SMA、PCNA、FN的表达。结果与模型组相比,治疗组肾间质纤维化程度明显减轻,肾间质α-SMA、PCNA、FN的表达也明显减少。结论STI571能够下调肾组织α-SMA表达水平,抑制肾间质细胞增殖活化,减少肾间质细胞外基质的沉积,对UUO小鼠早期肾间质纤维化有一定防治作用。

Objective To evaluate the effect of Imatinib mesylate （ STI571 ） on the process of renal interstitial fibrosis following unilateral ureteral obstruction in mice. Methods 40 male mice were randomly assigned to four groups： sham operation group, UUO group, and UUO treatment group in which mice receiving 80, 160 mg ·kg^-1·d^-1 STI571 after operation. All mice were killed at the 8th day after operation. Renal tissue histological changes were observed. The content of total collagen from each group was examined by acidolysis and chromatometry. Meanwhile, the de novo expression of a-smooth muscle actin （α-SMA） ,proliferating cell nuclear antigen（PCNA） and fibronectin（FN） in tissues were assessed by immunohistochemistry. Results Compared to UUO group, Imatinib mesylate significantly ameliorated the histological changes of the UUO renal tissue. The expression of α-SMA,PCNA and FN were decreased significantly in the treatment groups. Conclusion Imatinib mesylate could downregulate the expression of α-SMA, PCNA and FN in the UUO mice. It suppresses the proliferation and activation of renal interstitial cells and reduces the deposition of extracellular matrix in the interstitium as well. This demonstrates that Imatinib mesylate possesses the potential ability to inhibit early renal interstitium fibrosis caused by UUO in mice.