普乐可复和环孢素A对肝细胞分泌白蛋白作用的影响  

Effects of tacrolimus and cyclosporine on albumin secretion in cultured human hepatocyte

作　　者：李瑛[1] 刘志红[2] 黄燕飞[2] 黎磊石[2] 刘伏友[1] 彭佑铭[1] 

机构地区：[1]中南大学湘雅二医院肾内科,长沙410011 [2]南京军区南京总医院解放军肾脏病研究所,南京210002

出　　处：《中南大学学报（医学版）》2006年第3期387-391,共5页Journal of Central South University ：Medical Science

摘　　要：目的：研究细胞因子及普乐可复（FK506）和环孢素A（CSA）对肝细胞分泌白蛋白的影响。比较FK506和CSA对IL-6抑制肝细胞分泌白蛋白的作用。方法：分别用IL-6，IL-2和IL-10（0-10μg／L）以及FK506和CSA（1-100μg／L）体外刺激人肝癌细胞株（HepG2）48h；另外用IL-6（5μg／L）刺激HepG2细胞，同时分别加入FK506和CSA（0.1-10μg／L）刺激细胞48h，采用全自动生化仪检测FK506和CSA组细胞上清中乳酸脱氢酶（LDH）的量，采用放射免疫法检测各组细胞上清白蛋白的量。结果：IL-6能明显降低HepG2细胞上清中白蛋白的水平，且在一定范围内呈剂量依赖性，IL-6为5μg／L时白蛋白的分泌量达最低（P〈0.05）。IL-2，IL-10和FK506对HepG2细胞白蛋白的分泌无明显影响，CSA能轻度降低HepG2细胞白蛋白的分泌，且当CSA为10和100μg／L时差异有统计学意义（P〈0.05）。FK506明显减少HepG2细胞释放LDH（P〈0.05），CSA则轻度增加HepG2细胞分泌LDH（但P〉0.05）。另外，FK506能减轻IL-6抑制HepG2细胞分泌白蛋白的作用（P〈0.01），但CSA对此无作用。结论：IL-6而非IL-2和IL-10能明显抑制HepG2细胞分泌白蛋白，FK506而非CSA能减轻肝细胞的损伤，并能减轻IL-6抑制肝细胞分泌白蛋白的作用，这为FK506用于治疗免疫性肾脏病低白蛋白血症提供了的理论依据。Objective To investigate the effects of inflammation cytokines, tacrolimus （FK506） and cyclosporine （CSA） on albumin secretion, and the effects of FK506 and CSA on the IL-6 induced suppression of albumin synthesis in cultured human hepatocytes. Methods Human hepatoma cell lines （HepG2 cells ） were separately cultured with IL-6, IL-2 and IL-10 （0 - 10 μg/ L） and FK506, CSA （0 - 100 μg/L） for 48 h. In another experiment, HepG2 cells were stimula- ted with different doses of FK506 and CSA （0 - 10 μg/L） in the presence of IL-6 （5 μg/L） for 48 h. Albumin levels in the supematant of all groups were measured by radioimmunoassay （RIA）. The concentration of LDH secreted by cells stimulated with FK506 and CSA were detected with spectrophotometry. Results For cultured HepG2 cells, IL-6 significantly decreased albumin levels in a dose-dependent manner （P 〈0.01 ）, and the maximal inhibition occurred at 5 μg/L. CSA mildly decreased albumin levels and a significant reduction in albumin production was first visible at 10 μg/ L （P 〈0.05 ）. In contrast, IL-2, IL-10 and FK506 did not significantly influence albumin production （P 〉 0.05 ）. FK506 obviously decreased LDH levels in the supematant （P 〈 0.05） and attenuated IL-6 induced suppression of albumin synthesis （P 〈 0.01 ）. But CSA slightly increased LDH concentration and could not block the IL-6 induced decrease of albumin synthesis （ P 〉 0.05）. Conclusion IL-6 but not IL-2 and IL-10 suppressed the production of hepatic albumin in vitro. FK506 protected against the suppression of hepatic albumin synthesis caused by IL-6, suggesting its potential role in improving hypoalbuminaemia in immune glomerulonephritis.

关 键 词：低白蛋白血症 炎症细胞因子 肝细胞 普乐可复 环孢素A 

分 类 号：R692.9[医药卫生—泌尿科学]