肾病综合征患儿中性粒细胞凋亡、细胞因子水平及Bcl-2的表达

Relationship between the apoptosis of neutrophil and the levels of cytokines and expression Bcl-2 gene in patients with ne- phrotic syndrome.

【目的】观察肾病综合征(nephroticsyndrome,NS)患者外周血中性粒细胞(polymorphonuclearneutrophil,PMN)凋亡情况,并检测外周血中细胞因子IL-8、IL-6、TNF-α、NO水平的变化及Bcl-2的基因表达,探讨他们之间的关系。【方法】采用流式细胞术检测28例NS病人外周血PMN凋亡及Bcl-2基因的表达,ELISA法检测血清细胞因子IL-8、IL-6、TNF-α、NO水平。【结果】NS患者PMN凋亡率及Bcl-2的表达分别为单纯型(46.09±6.26)％、(17.92±2.22)％和肾炎型(28.63±5.56)％、(38.27土2.57)％,差异均有显著性(P<0.01或<0.05)。活动期NS患者PMN凋亡率为(45.62±13.22)％,明显低于缓解期NS患者(63.20±7.85)％。活动期NS患者外周血中IL-8、ILL-6、TNF-α、NO水平均高于缓解期(P<0.01或<0.05),且与PMN凋亡呈负相关(P<0.001),与病情呈正相关。【结论】NS患者PMN凋亡延迟,且与病情及疗效密切相关,各种炎性细胞因子产生过多及Bcl-2的表达上调可能是导致PMN凋亡延迟的重要机制,适度调控PMN凋亡,有可能成为治疗NS的有效途径。

[Objective] To observe the changes of polymorphonuclear neutrophil (PMN) apoptosis and the levels of inflammatory cytokines and expression of Bcl-2 gene of neutrophil in patients with nephrotic syndrome(NS)and to study the relationship between them. [Methods] The apoptosis and expression of Bcl-2 gene of neutrophil in 28 patients with NS at the active stage and 20 patients with NS at the remission stage were determined with flow cytometry. The inflammatory cytokines were tested with ELISA method. [Results] The percentage of neutrophil apoptosis in the patients with NS at the active stage(45. 62±13. 22)% was obviously lower than that of the patients with NS at the remission stage(63. 20±7. 85)%(P<0. 01 or <0. 05). Significant differences in apoptosis and expression of Bcl-2 of neutrophil were found among the different clinical stages of active NS patients. The levels of IL-8, TNF-a, IL-6 , NO in patients with NS at the active stage were higher than those of the patients with NS at the remission stage significantly, and the increasing levels of inflammatory cytokines in active NS patients were negatively correlated to the percentage of neutrophil apoptosis and positively correlated to the severity of NS. [Conclusions] The data demonstrated a delay in apoptotic process of neutrophil in active NS. The high expression of inflammatory cytokines and the up regulation of the expression of Bcl-2 gene may play an important role in the cause of inhibition of neutrophil apoptosis which prolong the functional life span of neutrophil. Therefor the delayed apoptotic neutrophils produce more inflammatory mediators participating in the damage of colonic tissue. For this reason, adjusting the expression of cytokines and moderately controlling the apoptosis of neutrophil further may be a new therapeutic target for NS.