活性维生素D3在雷帕霉素预处理系膜细胞增殖与凋亡中的作用

摘要

Objective To investigate the effect of 1,25-dihydroxyvitamin D3 on proliferation and apoptosis of glomerular mesangial cells via the PI3K/Akt/mTOR signal pathway. Methods The normal control group, 1,25-dihydroxyvitamin D3 (10-8 mol/L) group, rapamycin (0.1 μg/mL) group and the rapamycin in combination with 1,25-dihydroxyvitamin D3 group. The cell proliferation was measured by cell counting kit-8 assay. The cell cycle and cell apoptosis were detected by flow cytometry assay , respectively. Results Compared with the normal control group, the proliferation of glomerular mesangial cells was significantly inhibited in the 1 ,25-dihydroxyvitamin D3 group, in the rapamycin group and in the rapamycin in combination with 1,25-dihydroxyvitamin D3 group. The cells at G1 phase were significantly increased, but the cells at S phase were significantly decreased, with significant increase of cell apoptosis rate. Compared with the 1,25-dihydroxyvitamin D3 group, the proliferation of human glomerular mesangial cells was significantly inhibited in the rapamycin group and in the rapamycin in combination with 1,25-dihydroxyvitamin D3 group. Compared with the rapamycin group, the cells at G1 phase were significantly increased and the cells at S phase were significantly decreased in the rapamycin in combination with 1,25-dihydroxyvitamin D3 Group. Conclusions 1,25-dihydroxyvitamin D3 inhibits cell proliferation and promotes human glomerular mesangial cell apoptosis of human glomerular mesangial through the PI3K/Akt/mTOR signal pathway. 1,25-dihydroxyvitamin D3 and rapamycin can synergistically inhibit the proliferation of human glomerular mesangial cells.%目的：探讨活性维生素 D3[1，25（OH）2D3]通过 PI3K/Akt/mTOR 信号通路对人系膜细胞增殖与凋亡的调节作用。方法：体外培养人系膜细胞，随机分为正常对照组、1，25（OH）2D3（10-8 mol/L）组、雷帕霉素（0．1μg/mL）组、雷帕霉素联合1，25（OH）2D3组，采用CCK-8法检测各组干预48 h 后对人系膜细胞增殖的影响，流式细胞术检测各组干预48 h后对人系膜细胞细胞周期与细胞凋亡的影响。结果：与正常对照组比较，1，25（OH）2D3组、雷帕霉素组、雷帕霉素组联合1，25（OH）2D3组均能显著抑制系膜细胞的增殖， G1期细胞均显著增加，S 期细胞均显著减少，且细胞凋亡率均显著增加（均 P＜0．01）；与1，25（OH）2D3组比较，雷帕霉素组及雷帕霉素联合1，25（OH）2D3组均能显著抑制系膜细胞的增殖，G1期细胞显著增加，S 期细胞显著降低，细胞凋亡率显著增加（均 P＜0．01）；与雷帕霉素组比较，雷帕霉素联合1，25（OH）2D3组能显著抑制系膜细胞的增殖，G1期细胞显著增加，S 期细胞显著降低，但细胞凋亡率显著降低（P ＜0．01）。结论：1，25（OH）2D3可能通过 PI3K/Akt/mTOR 信号通路抑制人系膜细胞的增殖，促进其凋亡，且1，25（OH）2D3可协同雷帕霉素抑制人系膜细胞的增殖。