老年男性心功能不全患者外周血CD_4^+CD_(45)RA^+和CD_4^+CD_(45)RO^+的变化及免疫调节的干预作用

Analysis of changes in percentage of phenotype CD_4^+CD_(45)RA^+ and CD_4^+CD_(45)RO^+ in peripheral blood and effect of immunomodulation in aged male patients with chronic cardiac insufficiency

目的:评估外周血老年男性慢性心功能不全(CCI)患者CD4+T淋巴细胞细胞初始T细胞(CD4+CD45RA+)和记忆T细胞(CD4+CD45 RO+)表型的变化,并探讨免疫调节治疗对CD4+CD45RA+和CD4+CD45RO+亚型影响及可能的治疗机制。方法:155例老年男性,分成3组:正常对照组(n=41);CCI干预组(n=60),接受常规治疗和胸腺五肽治疗(20 mg,i.m.,隔日一次,共3月);CCI对照组(n=54),只给予常规治疗。所有患者在治疗前后均行超声心动图检测,并采集外周血。分离外周血T淋巴细胞并采用流式细胞学检测技术测定CD4+、CD8+亚群分布和CD4+CD45RA+、CD4+CD45RO+表型的变化。非均相免疫法检测血浆N末端前脑利钠肽前体(NT-proBNP)水平,免疫比浊法检测C反应蛋白(CRP)。结果:与对照组相比,CCI组左室射血分数(LVEF)和CD4+CD45 RO+水平下降;而LVEDD、NT-proBNP、CRP、CD4+和CD4+CD45RA+水平升高;CD8+水平无明显改变。NT-proBNP、CRP、CD4+/CD8+和CD4+CD45RA+/CD4+CD45RO+水平同LVEF呈负相关。常规抗心功能不全治疗结合免疫调节较单纯抗心功能不全治疗能更好地降低CD4+/CD8+和CD4+CD45 RA+/CD4+CD45 RO+水平而改善心功能。结论:CD4+和CD8+、CD4+CD45RA+和CD4+CD45RO+水平变化提示CD4+T淋巴细胞亚群及其表型在CCI过程中发挥重要作用,免疫调节CD4+淋巴细胞表型变化可能是免疫治疗CCI的重要方向之一。

Objective： Autoimmunity participates in chronic heart failure （CCI）, it is CD4 ^＋ T lymphocytes that mainly induces myocardial infiltration and the progression of the disease. The purpose of this research is to assess changes of CD4 ^＋ , CD8 ^＋ T lymphocyte subset, and to investigate the immunomod^＋atory effects on subsets of CD4 ^＋ , CD8 ^＋ and phenotype of CD4 ^＋ CD45 RA ^＋ and CD4 ^＋ CD45 RO ^＋ and the possible therapeutic mechanism. Methods： The participant were 155 aged men among whom 94 cases were diagnosed as CCI and heart function of the rest 41 cases were normal. All patients underwent echocardiography examination and were collected peripheral blood before and after treatment. Serum N terminal pro-brain natriurefie pepfide （NT-proBNP） levels were detected by heterogeneous immtmoassay. Serum C reactive protein （CRP） were measured by irmnunoturbidimetry assay. T lymphocytes in peripheral blood were separated and determined distribution of CD4 ^＋ , CD8^＋ , CD4^＋ CD45RA^＋ .CD4 ^＋ CD45RO＋ using flowcytometry. Participants were divided into 3 groups： the CCI intervention group, who received regular therapy and thymopendin （20 mg intramuscular injection, once every other day for 3 month; n = 60） , the CCI control group, who received regular therapy （ n = 54） and 41 healthy individual older than 57 years of age, who served as nonnal controls. Results： Compared with the control group, left ventricular ejection fraction （LVEF） and CD4 ^＋ CD4sRO＋ levels decreased, left ventricular end diastolic diameter （LVEDD）, NT-proBNP, CRP, CD4 ^＋ , CD4 ^＋ CD45RA^＋ , CD4 ^＋/CD8 ^＋ , CD4 ^＋ CD45RA^＋/CD4 ^＋ CD45RO^＋ levels were obviously higher in CCI group. Distribution of CD8 ^＋ was not significantly changed. The level of NT-proBNP, CRP, CD4 ^＋/CDs ^＋ , CD4 ^＋ CD45RA^＋/CD4^＋ CD45 RO ^＋ was negatively correlated with LVEF. LVEF could be much improved via decreasing distribution of CD4 ^＋/CDs ^＋ , CD4 ^＋ CD45 RA ^＋/CD4 ^＋CD45RO in CCI intervention group than in CCI control group. Conclusion： The changes of CD4 ^＋/CD8 ^＋ and CD4 ^＋ CD45RA^＋/CD4 ^＋ CD45RO＋ suggest that CD4 ^＋ T lymphocyte subset and its phenotype play an important role in the process of CCI. The regulation of CD4 ^＋ T lymphocyte and its phenotype may be one of the strategy in the treatment of CCI.