摘要: |
目的:观察霉酚酸酯(MMF)对多囊肾囊肿衬里上皮细胞增殖和凋亡的影响,并与雷帕霉素(RAPA)比较。方法:采用原代培养的人多囊肾囊肿衬里上皮细胞,用不同浓度MMF和RAPA分别作用48 h和72 h。MTT法检测细胞增殖情况;流式细胞术检测细胞周期变化;Annexin Ⅴ-FITC流式细胞术测定细胞凋亡率;透射电镜观察细胞超微结构改变。结果:MMF和RAPA均能抑制囊肿衬里上皮细胞增殖,呈明显的量效和时效关系。作用48 h后MMF使细胞阻滞在S期,RAPA使细胞阻滞在G0/G1期。MMF和RAPA均可诱导细胞凋亡,最大凋亡率分别为(5.53±0.27)%和(4.36±0.10)%;电镜下可见典型的凋亡改变。结论:MMF与RAPA相比同样能明显抑制囊肿衬里上皮细胞增殖,诱导细胞凋亡,但其对细胞增殖的抑制作用较RAPA弱。 |
关键词: 霉酚酸酯 雷帕霉素 多囊肾 囊肿衬里上皮细胞 细胞增殖 细胞凋亡 |
DOI:10.3724/SP.J.1008.2008.00921 |
投稿时间:2007-12-26修订日期:2008-05-12 |
基金项目:国家自然科学基金(30570867,30330640,30271523). |
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Comparison between effects of mycophenolate mofetil and rapamycin on proliferation and apoptosis of cyst-lining epithelial cells of ADPKD patients |
ZHANG Tong,FU Li-li,MEI Chang-lin* |
(Department of Nephrology,Kidney Institute of PLA,Second Military Medical University,Shanghai 200003,China) |
Abstract: |
Objective:To investigate the effect of mycophenolate mofetil(MMF)on proliferation and apoptosis of cyst-lining epithelial cells in patients with autosomal dominant polycystic kidney disease (ADPKD),and to compare its effect with that of rapamycin (RAPA)in vitro.Methods: Primary cultured cyst-lining epithelial cells were treated with MMF and RAPA at different concentrations(0,0.005,0.05,0.5,5 μg/ml)for 48 h or 72 h.The inhibitory effects of them on the cells were evaluated by MTT assay; the cell cycle distribution and apoptotic ratio were determined by flow cytometry.The morphological changes of cyst-lining epithelial cells were observed under transmission electron microscope.Results: Both MMF and RAPA significantly inhibited the proliferation of cyst-lining epithelial cells in a dose- and time-dependent manner.After 48 h treatment,the cells were blocked at S phase by MMF and at G0/G1 phase by RAPA.Both drugs induced cell apoptosis,with the maximal apoptotic rate being (5.53±0.27)% for MMF and (4.36±0.10)% for PAPA.Typical morphological changes of apoptotic cells were observed under electron microscope.Conclusion: MMF can effectively inhibit proliferation and induce apoptosis of cyst-lining epithelial cells,but its inhibitory effect is weaker than that of RAPA. |
Key words: mycophenolate mofetil rapamycin polycystic kidney disease cyst-lining epithelial cell cell proliferation apoptosis |