血管内皮生长因子C参与肾间质纤维化的进程

目的探讨血管内皮生长因子C（VEGF-C）在大鼠。肾小管上皮细胞向间充质细胞转化（EMT）过程中的变化及其作用通路，并利用动物模型研究血管紧张素Ⅱ受体拮抗剂替米沙坦对VEGF-C的影响，从而探讨VEGF-C在肾间质纤维化中的作用。方法体外培养大鼠肾小管上皮细胞（NRK52E），用转化生长因子B1（TGF-β1）孵育不同时间，观察其对VEGF-C、上皮型钙黏蛋白（E-cadherin）、波形蛋白（vimentin）、磷酸化AKT（P-AKT）等表达的影响，并在TGF-131作用同时加入PBK抑制剂Wortmannin，观察上述指标的变化；用单侧输尿管结扎术（UUO）制作SD大鼠肾间质纤维化模型，将21只大鼠随机分为假手术组、模型组和替米沙坦治疗组，每组7只。2周后，用免疫组织化学法检测α平滑肌肌动蛋白（mSMA）及VEGF-C在肾组织的分布，用RT-PCR和Westernblot—ring法检测其mRNA和蛋白表达。结果TGF-β1促进EMT的同时促进VEGF-C的表达增加。加入Wortmannin后EMT被抑制，同时VEGF-C的表达减低。动物模型组α-SMA和VEGF-C表达较假手术组高，替米沙坦治疗组α-SMA和VEGF-C表达较模型组低。结论TGF-β1可通过P13K—AKT通路促进VEGF-C的表达，VEGF-C与α-SMA的变化有同步性，提示VEGF-C可能参与肾间质纤维化的进程。

Involvement of vascular endothelial growth factor C in progression of renal interstitial fibrosis

Objective To investigate the expression of vascular endothelial growth factor C （VEGF-C） during tubular epithelial-to-mesenchymal transition （EMT） as well as its correlation with angiotensin H receptor blockers in renal fibrosis, and then discuss the roles of VEGF-C in renal tubulointerstitial fibrosis. Methods Rat proximal renal tubular cell lines （NRK52E） were used to study the influence of TGF-β1 on the expression of VEGF-C, E-cadherin, vimentin, P-AKT at different exposure time points. The effect of TGF-β1 plus Wortmannin, the specific inhibitor of PI3K family, on the expression of VEGF-C, E-cadherin, vimentin, P-AKT was evaluated as well. Unilateral ureteral ob- struction （UUO） was adopted to produce models of renal tubulointerstitial fibrosis. Twenty-one rats were randomly assigned to sham operation group, UUO group, and telmisartan treatment group （7 rats per group）. Two weeks later, renal tissue histological changes of a-SMA and VEGF-C were observed. RT-PCR and Western blot were performed to detect the expression of α-SMA and VEGF-C at mRNA or protein level. Results TGF-β1 could develop EMT and promote the expression of VEGF- C. EMT was inhibited by Wortmannin, and the expression of VEGF-C was depressed at the same time. Compared to sham operation group, the expression of α-SMA and VEGF-C was increased significantly in UUO group. The expression levels of α-SMA and VEGF-C in treatment group were lower than in UUO group. Conclusions TGF-β1 up-regulates the expression of VEGF-C mainly through PI3K-AKT pathway. The expression of VEGF-C changes along with α-SMA. These results suggest that VEGF-C may play an important role in the progression of renal tubulointerstitial fibrosis.