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氧化苦参碱通过调节T淋巴细胞亚群抑制HBV转基因小鼠的病毒复制
Oxymatrine inhibits viral replication in HBV transgenic mice by regulating T lymphocyte subsets
- 第三军医大学学报 2018年40卷第5期 页码：415-419
- 作者机构：
1.421002 湖南 衡阳，南华大学附属南华医院感染科
2.421002 湖南 衡阳，南华大学附属南华医院消化内科
- 作者简介：
[阳学风，E-mail：651543263@qq.comYANG Xuefeng, E-mail: 651543263@qq.com
- 基金信息：湖南省自然科学基金重点项目(12JJ2058)
DOI：10.16016/j.1000-5404.201709193
中图分类号： R285.5;R373.21;R967收稿：2017-09-26，
修回：2017-12-06，
纸质出版：2018-03-15
- 稿件说明：
移动端阅览
谢靖婧, 阳学风. 氧化苦参碱通过调节T淋巴细胞亚群抑制HBV转基因小鼠的病毒复制[J]. 第三军医大学学报, 2018,40(5):415-419.
Jingjing XIE, Xuefeng YANG. Oxymatrine inhibits viral replication in HBV transgenic mice by regulating T lymphocyte subsets[J]. Journal of Third Military Medical University, 2018, 40(5): 415-419.
谢靖婧, 阳学风. 氧化苦参碱通过调节T淋巴细胞亚群抑制HBV转基因小鼠的病毒复制[J]. 第三军医大学学报, 2018,40(5):415-419. DOI： 10.16016/j.1000-5404.201709193.
Jingjing XIE, Xuefeng YANG. Oxymatrine inhibits viral replication in HBV transgenic mice by regulating T lymphocyte subsets[J]. Journal of Third Military Medical University, 2018, 40(5): 415-419. DOI： 10.16016/j.1000-5404.201709193.
摘要
目的
2
观察氧化苦参碱对HBV转基因小鼠病毒复制的作用，并探讨其是否与调节T淋巴细胞亚群有关。
方法
2
选取SPF级HBV转基因雄性小鼠36只，按随机数字表法分为模型组、氧化苦参碱组及拉米夫定组，每组12只，另取12只非转基因BALB/c雄性小鼠作为对照组。各组分别给予相应的药物治疗。观察各组小鼠肝脏组织病理变化，并检测血清及肝脏乙肝表面抗原(HBsAg)、乙型肝炎病毒HBV-DNA水平、血液T淋巴细胞亚群水平以及血清细胞因子水平。
结果
2
治疗后，与模型组比较，氧化苦参碱组与拉米夫定组血清及肝组织HBsAg、HBV-DNA水平较低(
P
<
0.05)，而氧化苦参碱组与拉米夫定组血清及肝组织HBsAg、HBV-DNA水平差异无统计学意义(
P
>
0.05)。与模型组比较，氧化苦参碱组与拉米夫定组血液CD3
+
、CD4
+
T淋巴细胞、CD4
+
/CD8
+
水平较高，且氧化苦参碱组＞拉米夫定组；CD8
+
T淋巴细胞水平较低，且氧化苦参碱组＜拉米夫定组(
P
<
0.05)；氧化苦参碱组与拉米夫定组血清干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)水平较高，且氧化苦参碱组＞拉米夫定组；白细胞介素-4(IL-4)水平较低，且氧化苦参碱组＜拉米夫定组，差异均有统计学意义(
P
<
0.05)。
结论
2
氧化苦参碱能有效抑制HBV转基因小鼠血清及肝组织HBsAg、HBV-DNA水平，该作用可能与调节T淋巴细胞亚群水平及Th1/Th2细胞因子水平、改善免疫功能有关。
Abstract
Objective
2
To determine the inhibitory effect of oxymatrine on viral replication in HBV transgenic mice
and investigate whether this effect is associated with regulating T lymphocyte subsets.
Methods
2
Thirty-six SPF male HBV transgenic mice were randomly divided into model group
oxymatrine group and lamivudine group
with 12 rats in each group. Another 12 non-transgenic BALB/c mice served as control group. All rats were given corresponding drug treatment. Pathological changes of liver tissue were observed in each group
and the levels of hepatitis B surface antigen (HBsAg)
hepatitis B virus deoxyribonucleic acid (HBV-DNA) in serum and liver
serum T lymphocyte subsets
and serum cytokine levels were detected.
Results
2
After treatment
the HBsAg and HBV-DNA levels in serum and liver were significantly lower in the oxymatrine group and lamivudine group than the model group (
P
<
0.05)
but there was no significant difference in t
he serum and liver levels between the oxymatrine group and lamivudine group (
P
>
0.05). Compared with the model control group
the proportions of CD3
+
and CD4
+
T lymphocytes and the ratio of CD4
+
/CD8
+
were obviously higher
while the proportion of CD8
+
T lymphocytes was quite lower in the oxymatrine group and lamivudine group
but the oxymatrine group had better above values than the lamivudine group (
P
<
0.05). What's more
the serum levels of interferon-γ (IFN-γ) and interleukin-2 (IL-2) were higher while that of interleukin-4 (IL-4) was lower in the oxymatrine group and lamivudine group than the model group
and the oxymatrine group also had better values (
P
<
0.05).
Conclusion
2
Oxymatrine can effectively inhibit the levels of HBsAg and HBV-DNA in serum and liver tissue of HBV transgenic mice
which may be mediated by regulating the proportions of T lymphocyte subsets and the levels of Th1/Th2 cytokines
and improving the immune function.
关键词
Keywords
references
BACKES S, JÄGER C, DEMBEK C J, et al . Protein-prime/modified vaccinia virus Ankara vector-boost vaccination overcomes tolerance in high-antigenemic HBV-transgenic mice[J ] . Vaccine, 2016, 34(7): 923-932. DOI:10.1016/j.vaccine.2015.12.060.
MACLACHLAN J H, COWIE B C. Hepatitis B virus epidemiology[J]. Cold Spring Harb Perspect Med, 2015, 5(5): a021410. DOI:10.1101/cshperspect.a021410.
张敏娜, 袁月, 貌盼勇, 等.中国2004-2013年病毒性肝炎发病与死亡趋势分析[J].中华流行病学杂志, 2015, 36(2): 144-147. DOI:10.3760/cma.j.issn.0254-6450.2015.02.010.
ZHANG M N, YUAN Y, MAO P Y, et al . Analysis on morbidity and mortality of viral hepatitis in China,2004-2013[J ] . Chin J Epidemiol, 2015, 36(2): 144-147. DOI:10.3760/cma.j.issn.0254-6450.2015.02.010.
BERG T, ZOULIM F, MOELLER B, et al . Long-term efficacy and safety of emtricitabine plus tenofovir DF vs . tenofovir DF monotherapy in adefovir-experienced chronic hepatitis B patients[J ] . J Hepatol, 2014, 60(4): 715-722. DOI:10.1016/j.jhep.2013.11.024..
LIU Y, QI X, ZENG Z, et al . CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice[J ] . Sci Rep, 2017, 7(1): 2796. DOI:10.1038/s41598-017-03070-8.
DI SCALA M, OTANO I, GIL-FARIÑA I, et al . Complementary effects of interleukin-15 and alpha interferon induce immunity in hepatitis B virus transgenic mice[J ] . J Virol, 2016, 90(19): 8563-8574. DOI:10.1128/JVI.01030-16.
BAO J J, LEE B P, STEPHENS L C, et al . Elevated expression of hepatic proliferative markers during early hepatocarcinogenesis in hepatitis-B virus transgenic mice lacking mdr1a-encoded P-glycoprotein[J ] . Mol Carcinog, 2000, 29(2): 103-111. DOI:10.1002/1098-2744(200010) 29:2 < 103::aid-mc7 > 3.0.co; 2-e.
GRAUMANN F, CHURIN Y, TSCHUSCHNER A, et al . Genomic methylation inhibits expression of hepatitis B virus envelope protein in transgenic mice: a non-infectious mouse model to study silencing of HBV surface antigen genes[J ] . PLoS ONE, 2015, 10(12): e0146099. DOI:10.1371/journal.pone.0146099.
MCFADDEN V C, SHALABY R E, IRAM S, et al . Hepatic deficiency of the pioneer transcription factor FoxA restricts hepatitis B virus biosynthesis by the developmental regulation of viral DNA methy lation[J ] . PLoS Pathog, 2017, 13(2): e1006239. DOI:10.1371/journal.ppat.1006239.
吴琴, 高云.氧化苦参碱药理作用的分子机制研究进展[J].中国药理学通报, 2015, 31(6): 759-762. DOI:10.3969/j.issn.1001-1978.2015.06.005.
WU Q, GAO Y. Research advances in molecular mechanism of pharmacological actions of oxymatrine[J]. Chin Pharmacol Bull, 2015, 31(6): 759-762. DOI:10.3969/j.issn.1001-1978.2015.06.005.
HUANG F, CAI P, WANG Y, et al . Up-regulation of brain-expressed X-linked 2 is critical for hepatitis B virus X protein-induced hepatocellular carcinoma development[J ] . Oncotarget, 2017. DOI:10.18632/oncotarget.19477.
ZHANG T Y, YUAN Q, ZHAO J H, et al . Prolonged suppression of HBV in mice by a novel antibody that targets a unique epitope on hepatitis B surface antigen[J ] . Gut, 2016, 65(4): 658-671. DOI:10.1136/gutjnl-2014-308964.
LOGGI E, GAMAL N, BIHL F, et al . Adaptive response in hepatitis B virus infection[J ] . J Viral Hepat, 2014, 21(5): 305-313. DOI:10.1111/jvh.12255.
ZHUO M, SONG L, TANG Y, et al . Vaccination with ubiquiti n-hepatitis B core antigen-cytoplasmic transduction peptide enhances the hepatitis B virus-specific cytotoxic T-lymphocyte immune response and inhibits hepatitis B virus replication in transgenic mice[J ] . Mol Med Rep, 2015, 12(3): 3591-3598. DOI:10.3892/mmr.2015.3834.
DEMBEK C, PROTZER U. Mouse models for therapeutic vaccination against hepatitis B virus[J]. Med Microbiol Immunol, 2015, 204(1): 95-102. DOI:10.1007/s00430-014-0378-6.
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