生化汤逆转甲氨蝶呤诱导的干扰素-γ免疫抑制作用

基金项目:国家自然科学基金项目(No.30901918,30973807);山东省博士基金项目(No.BS2009YY041);山东省自然科学基金项目(No.ZR2010HQ066,2008C101);山东省计生委项目(No.[2009]8);山东省中医药管理局项目(No.2009-173)

作者	单位
周宪宾	山东省医学科学院基础医学研究所山东省医药卫生中药免疫与肿瘤免疫重点实验室、山东省现代医用药物与技术重点实验室、免疫药理学实验室、山东省罕少见疾病重点实验室
姚成芳	山东省医学科学院基础医学研究所山东省医药卫生中药免疫与肿瘤免疫重点实验室、山东省现代医用药物与技术重点实验室、免疫药理学实验室、山东省罕少见疾病重点实验室
王丽	山东省医学科学院基础医学研究所山东省医药卫生中药免疫与肿瘤免疫重点实验室、山东省现代医用药物与技术重点实验室、免疫药理学实验室、山东省罕少见疾病重点实验室
王彬	山东中医药大学附属医院
李霞	山东省医学科学院基础医学研究所山东省医药卫生中药免疫与肿瘤免疫重点实验室、山东省现代医用药物与技术重点实验室、免疫药理学实验室、山东省罕少见疾病重点实验室
郝钰	山东省医学科学院基础医学研究所山东省医药卫生中药免疫与肿瘤免疫重点实验室、山东省现代医用药物与技术重点实验室、免疫药理学实验室、山东省罕少见疾病重点实验室
郭钰琪	山东省医学科学院基础医学研究所山东省医药卫生中药免疫与肿瘤免疫重点实验室、山东省现代医用药物与技术重点实验室、免疫药理学实验室、山东省罕少见疾病重点实验室
迟学芝	山东警察学院

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中文摘要:

目的观察生化汤对甲氨蝶呤(MTX)诱导的干扰素-γ(interferon-γ,IFN-γ)免疫抑制的逆转作用。方法 Balb/C孕鼠40只,随机分为对照组、生化汤组、MTX组、联合组,自妊娠第10天起分别给予生理盐水、生化汤、MTX、MTX联合生化汤处理,连续用药7天,末次给药后1h处死小鼠。计数各组孕鼠活胎数与死胎数,借以评价母胎排斥状态;采用流式细胞术胞内外因子双染色法检测孕鼠脾脏淋巴细胞中的IFN-γ+及CD3+CD4+IFN-γ+细胞比例,反转录聚合酶链式反应(RT-PCR)法检测脾脏单个核细胞中IFN-γ信使核糖核酸(mRNA)表达水平。结果与对照组比较,生化汤组死胎数略有增加(P>0.05),脾脏中IFN-γ+及CD3+CD4+IFN-γ+细胞阳性率分别升高了28.81%和35.61%(P<0.05),IFN-γmRNA表达升高(P<0.05);MTX处理后,死胎数明显增加,脾脏中IFN-γ+、CD3+CD4+IFN-γ+细胞比例较对照组分别降低了24.23%和26.77%,IFN-γmRNA表达明显降低(P<0.05)。MTX联合生化汤处理后,死胎数进一步增加,IFN-γ+、CD3+CD4+IFN-γ+细胞比例明显升高,较MTX组分别增加了64.96%、71.38%,IFN-γmRNA表达明显上调(P<0.05)。结论生化汤通过促进IFN-γ+Th1亚群分化,上调IFN-γ表达,逆转MTX对IFN-γ的抑制作用,进而促进母胎免疫排斥。

英文摘要:

Objective To observe the effect of Shenghua Decoction in reversing IFN-γ inhibition induced by methotrexate(MTX).Methods Pregnant Balb/C mice were randomly divided into the negative control group,Shenghua Decoction group,the MTX control group,and the MTX combined with Shenghua Decoction group.Pregnant mice in the 4 groups were respectively treated with normal saline(NS),Shenghua Decoction,MTX,and MTX combined with Shenghua Decoction for 7 successive days.Then mice were sarcrificed 1 h after the last administration.Living fetus and dead fetus were counted to assess meto-maternal rejection.The percentages of interferon-γ+(IFN-γ+) and CD3+CD4+IFN-γ+ cells in spleen lymphocytes of pregnant mice were double stained for cytometric analysis.At the same time IFN-γ message ribonucleic acid(mRNA) in the spleen mononuclear cells was detected by reverse transcription polymerase chain reaction(RT-PCR).Results Compared with the negative control group,the number of dead fetus increased significantly after the administration of Shenghua Decoction(P>0.05).The percentages of IFN-γ+ and CD3+CD4+ IFN-γ+ in spleen mononuclear cells were elevated by 28.81% and 35.61% respectively(both P<0.05).IFN-γ mRNA expression increased(P<0.05).After the administration of MTX,the number of dead fetus increased significantly.The percentages of IFN-γ+ and CD3+CD4+ IFN-γ+ in spleen mononuclear cells were reduced by 24.23% and 26.77% respectively compared with the negative control group.Besides,the expression of IFN-γ mRNA decreased obviously(P<0.05).However,after the administration of MTX in combination of Shenghua Decoction,the number of dead fetus was further added.Moreover,the percentages of IFN-γ+ and CD3+CD4+IFN-γ+ cells obviously increased.The increment was 64.96% and 71.38% respectively when compared with the MTX group,and the expression of IFN-γ mRNA was obviously up-regulated(P<0.05).Conclusion Shenghua Decoction showed reversing effect on MTX induced IFN-γ inhibition by promoting the differentiation of IFN-γ+Th1 subpopulation and up-regulating IFN-γ expression,thus promoting the feto-maternal immunological rejection.

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