从CD4+、CD8+T细胞免疫活化分子及其上游调控因子表达探究健脾祛湿法治疗艾滋病免疫调节机制

HIV/AIDS Chronic immune activation presenting with CD4+、 CD8+ T cell activation molecule expression are closely associated with the progression of AIDS, and increased mortality.Early research has shown that tonifying spleen kidney herbs can regulate the immune activation of CD4+、 CD8+ T cell, which was one of the clinical curative effect mechanism way on HIV/AIDS.Is this a common mechanism of traditional Chinese medicine treatment of HIV/AIDS?On this base,supporting by the national Chinese medicine pilot project to treat AIDS and national free HIV treatment clinic,this project interfering with Chinese medicine preparation with therapeutic principles of benefit the spleen and clearing damp,control by combination of Chinese medicine preparation and HAART, HAART only with 150 cases divided into three groups,observating for 12 months,testing with FCM (flow cytometry method),ELISA (enzyme linked immuno sorbent assay),RT-PCR (reverse transcription polymerase chain reaction),detects immune activation moculors CD38, HLA-DR,and their upstream regulatory factors IL-7、IFN-α on CD4+ and CD8+ cell, CD4+、 CD8+T cell count、HIV virus load at 0,6,12 month,analysizing the changes and relationship among these indexes and effect on the progress disease of AIDS, explores the mechanism of Chinese medicine preparation on AIDS from expressions of immune activation molecules and their upstream regulatory factors on CD4+ and CD8+ cell,provides foundation of evaluation of therapeutic effect and drug development on AIDS treating with Chinese medicine.

以CD4+、CD8+T细胞等细胞活化为表现的艾滋病慢性免疫活化与艾滋病病情进展、死亡率增加密切相关。前期研究显示，补脾益肾中药对艾滋病CD4+、CD8+T细胞免疫活化有调整作用，是该方药治疗艾滋病的疗效机制之一。这是否是中医药治疗艾滋病的共同免疫调节机制？基于此，本项目依托国家中医药治疗艾滋病试点项目和免费抗 HIV 治疗点，使用临床疗效肯定的健脾祛湿方药为干预药物，并与西药HAART、中药加 HAART做对照，采用FCM、ELISA、RT-PCR等方法，检测用药0、6、12个月CD4+、CD8+T细胞活化分子CD38、HLA-DR及其上游调控因子IL-7、IFN-α和CD4+、CD8+T细胞计数、HIV载量，从CD4+、CD8+T细胞活化分子及其上游调控因子表达及对艾滋病病程影响，探究健脾祛湿方药治疗艾滋病的免疫调节机理，为阐明中医药治疗艾滋病疗效机制、疗效评价和药物研发提供借鉴、依据。

本项目以艾滋病免疫激活状态相关的CD4+、CD8+T细胞活化分子CD38、HLADR及其上游调控因子IL-7、IFN-α为切入点，通过检测健康体检者和未服用抗病毒药物的HIV感染者的IFN-α和IL-7，显示两个指标在HIV感染者中升高，提示HIV感染者存在以IFN-α和IL-7升高为标志的免疫激活状态；检测单用HAART（简称西药组）和服用健脾祛湿中药（简称中药组）以及服用健脾祛湿中药和HAART药物（简称中西药组）的HIV/AIDS患者治疗前后的IFN-α、IL-7、CD38、HLA-DR以及CD4细胞计数和HIVRNA的变化，结果显示治疗后各组的IFN-α、IL-7、CD38、HLA-DR均下降，CD4细胞计数均增加，HIVRNA西药组和中西药组抑制率（低于检测线）较好，中药组不明显。结果提示健脾祛湿中药对CD4+、CD8+T 细胞免疫活化分子CD38、HLA-DR及其上游调控因子IFN-α、IL-7表达有下调、抑制作用，对CD4细胞计数有增加作用，对HIVRNA的抑制作用不明显。本项目从艾滋病 CD4+、CD8+T 细胞免疫活化分子及其上游调控因子表达的影响的角度，研究中医药治疗艾滋病在免疫活化方面的的作用机制，为中医药治疗艾滋病的机制研究、疗效评价提供参考。