[环孢素和他克莫司对乙型肝炎病毒体外复制的影响：一项比较研究]

[Effects of ciclosporin and tacrolimus on replication of hepatitis B virus in vitro: a comparative study].

作者信息

Xia Wei-liang, Xie Hai-yang, Shen Yan, Wu Li-ming, Zhang Feng, Zheng Shu-sen

机构信息

Department of Hepatobiliary Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2006 Jan 10;86(2):111-5.

PMID:16620716

Abstract

OBJECTIVE

To investigate the effects of ciclosporin (CsA) and tacrolimus (FK506) on replication of hepatitis B virus (HBV) in vitro.

METHODS

HBV genome permanently transfected human liver cancer cells of the line HepG2.2.15 were cultured. CsA and FK506 at different concentrations were added into the culture fluid so as to identify the nontoxic concentrations by MTT method. Then the HepG2.2.15 cells were treated by CsA and FK506 at different nontoxic concentrations respectively for 4 days. ELISA was used to detect the HB surface antigen (HBsAg) and HB e antigen (HBeAg) in the supernatant. The relative replication level of HBV DNA was detected by slot blot analysis.

RESULTS

MTT method confirmed that the nontoxic concentrations of CsA and FK506 were 0-40.0 microg/ml and 0-400 ng/ml respectively. After the treatment of CsA at the concentration of 1.3, 2.5, and 5.0 microg/ml, in comparison to the control group, the suppression rates of HBsAg expression in the HepG2.2.15 cells were 16.5% +/- 9.4%, 21.5% +/- 8.9%, and 33.1% +/- 5.3% respectively (all P < 0.05); the suppression rates of HBeAg expression in the HepG2.2.15 cells were 7.8% +/- 2.2%, 11.0% +/- 2.3%, and 20.8% +/- 1.5% respectively (all P < 0.05); and the HBV DNA replication levels were 56 +/- 16, 42 +/- 11, and 40 +/- 10 respectively (P > 0.05, P < 0.05, and P > 0.05). However, FK506 at different nontoxic concentrations showed no significant inhibitory effect on the levels of HBsAg, HBeAg, and HBV DNA.

CONCLUSION

CsA dose-dependently inhibits the HBV replication in vitro, and FK506 does not exercise similar effects.

摘要

目的

研究环孢素（CsA）和他克莫司（FK506）对乙型肝炎病毒（HBV）体外复制的影响。

方法

培养稳定转染HBV基因组的人肝癌细胞系HepG2.2.15。将不同浓度的CsA和FK506加入培养液中，采用MTT法确定无毒浓度。然后分别用不同无毒浓度的CsA和FK506处理HepG2.2.15细胞4天。采用ELISA法检测上清液中的乙肝表面抗原（HBsAg）和乙肝e抗原（HBeAg）。采用斑点杂交分析检测HBV DNA的相对复制水平。

结果

MTT法证实CsA和FK506的无毒浓度分别为0～40.0μg/ml和0～400ng/ml。用1.3、2.5和5.0μg/ml浓度的CsA处理后，与对照组相比，HepG2.2.15细胞中HBsAg表达的抑制率分别为16.5%±9.4%、21.5%±8.9%和33.1%±5.3%（均P<0.05）；HepG2.2.15细胞中HBeAg表达的抑制率分别为7.8%±2.2%、11.0%±2.3%和20.8%±1.5%（均P<0.05）；HBV DNA复制水平分别为56±16、42±11和40±10（P>0.05、P<0.05和P>0.05）。然而，不同无毒浓度的FK506对HBsAg、HBeAg和HBV DNA水平均无明显抑制作用。