中文摘要：

目的研究多囊蛋白-1氨基段（PC-INF）融合蛋白对大鼠肾小球系膜细胞（RMC）Ⅳ型胶原及其降解调控基因表达的影响。方法用实时荧光定量RT-PCR法检测PC-1NF融合蛋白对RMCIV型胶原和细胞外基质（ECM）降解调控基因基质金属蛋白酶、金属蛋白酶1组织抑制剂（MMP-2、TIMP-1）表达的作用。ELISA方法检测培养的细胞上清液中Ⅳ型胶原含量的变化。免疫细胞化学方法观察融合蛋白对细胞核因子c-jun和c-fos表达的影响。Western印迹检测融合蛋白对蛋白激酶C（PKC）-α信号转导通路的影响。结果4mg／LPC-1NF融合蛋白作用48h后，RMCⅣ型胶原mRNA从（103±16）降至（82±11）拷贝，106GAPDH，与对照组比较差异有统计学意义（P〈0．05），培养上清液中的IV型胶原含量也明显降低；MMP2mRNA从（1150±90）升至（2770±）拷贝，106GAPDH，与对照组比较差异有统计学意义（P〈0．01），而TIMP-1mRNA从（5530±480）降至（3040±370）拷贝，106GAPDH，与对照组差异有统计学意义（P〈0．01）。DAB染色显示，融合蛋白作用后，RMC的c-jun和c-fos表达受到明显抑制。RMC经不同浓度PC-1NF融合蛋白作用48h后，随着融合蛋白浓度升高。PKC-α的表达逐渐减弱。结论PC-1NF融合蛋白可通过上调促进ECM降解的MMP-2和抑制ECM降解的TIMP-1之间的比值而促进Ⅳ型胶原降解；还可能通过PKC-α信号转导通路，抑制c-ju．和c-fos表达，从而抑制RMC的增殖和ECM的合成。

英文摘要：

Objective To investigate the effect of N-terminal fragment（LRR-WSC） fusion protein of polycystin-1 （PC-1NF） on collagen Ⅳ synthesis and degradation in rat glomerular mesangial cells and to explore its mechanism. Methods Rat glomerular mesangial cells were treated with different concentrations of PC-1NF in vitro. The mRNA expression of type Ⅳ collagen, metalloproteinase 2 （MMP-2） and tissue inhibitor of metalloproteinase 1 （TIMP-1） were detected by real-time fluorescence quantitative PCR. The concentration of type Ⅳ collagen was determined by ELISA. The expression level of c-fos and c-jun was examined by immunocytochemistry. The expression of PKC-α was detected by Western blot. Results After treatment with 4 mg/L PC-1NF for 48 hours, the mRNA level of hype Ⅳ collagen was downregulated [（82±11） copies per million GAPDH] compared with that in the control [（103±16） copies per million GAPDH] （P〈0.05）, so was the protein level of type Ⅳ collagen. The mRNA level of TIMP-1 was significantly decreased [（3040±370） copies per million GAPDH] compared with that in the control [（5530±480） copies per million GAPDH] （P〈0.01）. However, the mRNA level of MMP-2 [（2770±170） copies per million GAPDH] was significantly increased compared with that in the control [（1150±90） copies per million GAPDH] （P〈0.01）. Meanwhile, PC-1 NF fusion protein treatment resulted in decreased protein levels of c-jun, c-fos and PKC-α. Conclusions PC-1 NF fusion protein may induce collagen Ⅳ degradation through increasing the ratio of MMP-2 to TIMP-1 in rat mesangial cells, inhibit c-jun and c-fos expression by modulating the PKC-ot synthesis, and then decrease the production of collagen Ⅳ in rat glomerular mesanglal cells.