羟甲基戊二酰辅酶A还原酶抑制剂对多囊肾病囊肿衬里上皮细胞增殖抑制及其机制的研究

目的 探讨羟甲基戊二酷辅酶 Ａ（ＨＭＧ ＣｏＡ）还原酶抑制剂对常染色体显性遗传型多囊肾病（ＡＤＰＫＤ）囊肿衬里上皮细胞的作用及其机制。方法 噻唑蓝（ＭＴＴ）法检测细胞增殖，免疫印迹法检测细胞膜ｐ２１ｒａｓ的表达．免疫细胞化学检测细胞核ｃ－ｆｏｓ、ｃ－ｊｕｎ的表达。结果ＡＤＰＫＤ囊肿衬里上皮细胞经 ＨＭＧ ＣｏＡ还原酶抑制剂处理后，细胞增殖受到显著抑制（Ｐ＜０．０１），细胞膜 ｐ２１ｒａｓ蛋白表达下调，细胞核ｃ－ｆｏｓ、ｃ－ｊｕｎ的表达显著下降（Ｐ＜０．０１）。结论 ＨＭＣ ＣｏＡ还原酶抑制剂能抑制ＡＤＰＫＤ囊肿衬里上皮细胞的增殖，其机制可能与抑制细胞内ｒａｓ蛋白的异戊二烯化并阻断ｒｓ介导的信号转导有关。

Antiproliferative effect of HMG CoA reductase inhibitor on ADPKD cyst-lining epithelial cell and its mechanism

Objective To investigate the antiproliferative effect of HMG CoA reductase inhibitor on ADPKD cyst-lining epithelial cells and its possible mechanism. Methods Cell viability was assayed by MTT. Membrane-bounded p2lras was detected by immunoblotting. The expression of c-jun and c-fos was examined by immunocytochemistry. Results After ADPKD cyst-lining epithelial cells were exposed to HMG CoA reductase inhibitor, proliferation was markedly inhibited( P < 0 . 01) . Immunoblot analysis revealed that lovastatin decreased the amount of membrane bound-p21 ras. Immunocytochcemistry revealed that the expression of c-jun and c-fos decreased significantly( P < 0.01). Conclusions HMG CoA reductase inhibitor can inhibit the proliferation of .ADPKD cyst-lining epithelial cell. This effect is dose-dependent and is mediated via inhibition of the p21 ras isoprenylation and ras-dependent signal cascade.