霉酚酸酯与雷帕霉素对多囊肾囊肿衬里上皮细胞增殖和凋亡影响的比较  

Comparison between effects of mycophenolate mofetil and rapamycin on proliferation and apoptosis of cyst-lining epithelial cells of ADPKD patients

作　　者：张彤[1] 付莉莉[1] 梅长林[1] 

机构地区：[1]第二军医大学长征医院肾内科,解放军肾脏病研究所,上海200003

出　　处：《第二军医大学学报》2008年第8期921-924,共4页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(30570867,30330640,30271523)~~

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;AnnexinⅤ-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。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.

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 

分 类 号：R692[医药卫生—泌尿科学]