不同透析膜对维持性血液透析患者外周血Ｔ细胞凋亡的影响

目的 研究终末期肾病(ESRD)患者外周血T细胞凋亡、Bcl-2和Fas的表达、Th1及Th2类细胞因子特征以及不同透析膜对维持性血液透析患者T细胞凋亡的影响。 方法 研究对象包括ESRD未透析(ND)患者10例；维持性血液透析(HD)的患者45例，分别用醋酸纤维素膜(CA)、低通聚砜膜(PS-LF)、高通聚砜膜(PS-HF)进行透析；以及健康对照(C)8例。上述研究对象的外周血T细胞经植物凝集素(PHA)刺激培养24 h后，应用流式细胞术检测其凋亡情况；免疫组化检测T细胞Bcl-2、Fas的表达；ELISA检测细胞培养上清IFN-γ及IL-4的水平。 结果 ND组及HD组T细胞凋亡率高于C组的(6.82±1.64)%。HD各组T细胞的凋亡率以CA组的(12.26±1.21)%最高，PS-HF组(9.00±0.89)%最低(P < 0.05)。ND组及HD组外周血T细胞Bcl-2的表达低于C组(P < 0.05)，Fas的表达高于C组(P < 0.05)；相关分析显示T细胞凋亡与Fas的表达呈正相关，与Bcl-2呈负相关。ND组及HD组IFN-γ的水平均低于C组(P < 0.05)，与T细胞凋亡呈负相关；IL-4的水平高于C组 (P < 0.05)，与T细胞凋亡呈正相关。 结论 ND组及HD组外周血T细胞凋亡加速，Bcl-2、Fas参与T细胞凋亡的发生。 ND组及HD组患者Th类细胞因子失衡，呈Th2细胞因子优势， Th类细胞因子参与T细胞凋亡的调控。HD患者的T细胞凋亡不仅与透析膜的生物相容性有关还与透析膜的通透性有关。

Influence of different dialysis membranes on the apoptosis of peripheral blood T lymphocytes of maintenance hemodialysis patients

Objective To investigate the apoptosis of T lymphocytes,the expression of Bcl-2,Fas on the peripheral blood T lymphocytes in end stage renal disease patients;and to explore the characteristics of Th1 /Th2 profile and the influence of dialysis membranes with different permeability on the apoptosis of T lymphocytes of maintenance hemodialysis patients. Methods The study included 10 non-dialyszed(ND)patients,45 maintenance hemodialysis patients with cellulose acetate(CA) membranes(13), low-flux polusulfone(PS-LF) membranes(16), high-flux polusulfone (PS-HF)membranes(16) and 8 healthy volunteers(C). The apoptosis of T lymphocytes,expression of Bcl-2,Fas on peripheral blood T lymphocytes cultured with phytohemagglutinin (PHA) stimulation for 24 hours were measured by flow cytometry and immunohistochemical. ELISA was performed for detecting the levels of IFN-γ and IL-4 in culture supernatants. Results In ESRD patients,the apoptosis of T lymphocytes was greater than that of group C. Group CA was greater than group PS-HF and group PS-LF(P < 0.05). The expression of Bcl-2 on T lymphocytes in ESRD patients was lower than that of group C(P < 0.05). There was negative correlation between the T lymphocytes apoptosis and Bcl-2. The expression of Fas on T lymphocytes in ESRD patients was greater than that of group C(P < 0.05),and it was positive correlated with T lymphocytes apoptosis. The level of IFN-γ of ESRD patients was decreased significantly compared with that in group C(P < 0.05), and there was negative correlation between T lymphocytes apoptosis and IFN-γ. IL-4 was increased in ESRD patients(P < 0.05) and it was positive correlated with T lymphocytes apoptosis. Conclusions The accelerated apoptosis of T lymphocytes in ESRD patients may be related to the expression of Bcl-2 and Fas of T lymphocytes. ESRD patients show a suppressed secretion of IFN-γ and an increased secretion of IL-4. T lymphocytes apoptosis of maintenance hemodialysis patients is influenced not only by the biocompatibility but also by the permeability of the dialysis membrane.