修回日期: 2006-12-01
接受日期: 2006-12-01
在线出版日期: 2007-02-28
目的: 探讨血清一氧化氮(NO)、IL-6、IL-10、肿瘤坏死因子(TNF)水平与肝硬化患者预后之间的关系.
方法: 采用硝酸还原酶法、ELISA法、双抗体夹心酶联免疫分析法分别测定30例健康对照者和56例肝硬化患者治疗前后的血清NO, IL-6, IL-10及TNF水平.
结果: 肝硬化患者的NO, IL-6, TNF水平显著升高, IL-10水平明显降低. 治疗后肝功能减退组的NO (129.21±27.32 μmol/L vs 92.18±25.68 μmol/L, P<0.05)、IL-6 (198.5±23.2 mg/L vs 147.0±19.1 mg/L, P<0.05)、TNF (179.2±23.5 pg/dL vs 121.4±17.5 pg/dL, P<0.05)水平较治疗前有显著升高, IL-10水平则明显下降(33.4±7.2 mg/L vs 51.6±18.5 mg/L, P<0.05), 而治疗后肝功能恢复组NO (58.63±12.25 μmol/L vs 94.36±23.45 μmol/L, P<0.05)、IL-6 (90.3±12.7 mg/L vs 148.5±15.8 mg/L, P<0.05)、TNF (78.2±14.3 pg/dL vs 124.9 ± 20.1 pg/dL, P<0.05)水平较治疗前降低(P<0.05), IL-10水平则明显升高(89.3± 18.9 mg/L vs 48.8±9.5 mg/L, P<0.05).
结论: NO, IL-6, IL-10, TNF与肝硬化患者预后有关.
引文著录: 孙群, 张强, 朱金水, 陈玮, 陈尼维. 一氧化氮、白介素、肿瘤坏死因子与肝硬化患者预后的关系. 世界华人消化杂志 2007; 15(6): 659-662
Revised: December 1, 2006
Accepted: December 1, 2006
Published online: February 28, 2007
AIM: To study the roles of serum nitric oxide (NO), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor (TNF) in the prognosis of patients with liver cirrhosis.
METHODS: Nitrate reductase assay and double-antibody sandwich enzyme-linked immunosorbent assay were used to examine the serum levels of NO, IL-6, IL-10 and TNF in 56 patients with liver cirrhosis before and after treatment, and 30 healthy individuals served as controls.
RESULTS: High levels of NO, IL-6, and TNF and low level of IL-10 were observed in patients with cirrhosis. After treatment, the serum levels of NO (129.21 ± 27.32 mmol/L vs 92.18 ± 25.68 mmol/L, P < 0.05), IL-6 (198.5 ± 23.2 mg/L vs 147.0 ± 19.1 mg/L, P < 0.05), and TNF (179.2 ± 23.5 pg/dL vs 121.4 ± 17.5 pg/dL, P < 0.05) were significantly elevated while the level of IL-10 (33.4 ± 7.2 mg/L vs 51.6 ± 18.5 mg/L, P < 0.05) was markedly decreased in patients with aggravated hepatic function as compared with those before therapy. However, the levels of NO (58.63 ± 12.25 mmol/L vs 94.36 ± 23.45 mmol/L, P < 0.05), IL-6 (90.3 ± 12.7 mg/L vs 148.5 ± 15.8 mg/L, P < 0.05) and TNF (78.2 ± 14.3 pg/dL vs 124.9 ± 20.1 pg/dL, P < 0.05) were decreased while the level of IL-10 (89.3 ± 18.9 mg/L vs 48.8 ± 9.5 mg/L, P < 0.05) was elevated in patients with improved hepatic function after treatment in comparison with those before treatment.
CONCLUSION: The serum levels of NO, IL-6, IL-10 and TNF are correlated with the prognosis of patients with liver cirrhosis.
- Citation: Sun Q, Zhang Q, Zhu JS, Chen W, Chen NW. Correlations of serum nitric oxide, interleukin-6, interleukin-10 and tumor necrosis factor levels with the prognosis of patients with liver cirrhosis. Shijie Huaren Xiaohua Zazhi 2007; 15(6): 659-662
- URL: https://www.wjgnet.com/1009-3079/full/v15/i6/659.htm
- DOI: https://dx.doi.org/10.11569/wcjd.v15.i6.659
肝硬化患者可出现一系列并发症, 严重危及人群健康, 如何判断其预后并给予积极治疗是临床医生关注的问题[1]. 一氧化氮(nitric oxide, NO)作为一种新型的细胞信使分子和氧自由基, 可能介导许多疾病的发生与发展[2]. IL-6, IL-10, TNF是一组细胞因子, 有实验表明, 他们在肝硬化的发生、发展中起着重要的作用, 而且其血清水平与肝硬化患者的Child-Pugh分级呈正相关[3]. 近年来, NO、细胞因子与肝硬化的关系正在受到越来越多的关注, 本研究旨在探讨血清NO, IL-6, IL-10和TNF水平与肝硬化患者预后之间的关系.
2003-09/2005-09本科住院的肝硬化患者56例, 其中男38例, 女18例, 年龄32-78(平均50.5)岁, 均经CT和内镜证实为肝硬化伴食道静脉曲张, 其中Child-Pugh B级26人, C级30人, 均采用古拉定、易善复及支链氨基酸等保肝治疗, 治疗后2 mo根据肝功能情况分成两组: 治疗后肝功能减退组32例, 治疗后肝功能好转或无变化组24例. 健康(HS)对照组共30例, 男16例, 女14例, 年龄范围25-60(平均45.3)岁. 对照组无消化系统疾病史及胃肠道症状; 无累及食管的全身性疾病, 精神状态良好.
所有肝硬化患者的血清NO, IL-6, IL-10和TNF水平与正常对照组及治疗前后比较见表1. 肝硬化患者的NO, IL-6, TNF水平较正常对照组显著升高(93.8±26.83 μmol/L vs 34.60±10.71 μmol/L, 147.8±26.3 mg/L vs 71.8±11.4 mg/L, 122.6±22.3 pg/dL vs 30.8±14.3 pg/dL), 差异有显著性(P<0.01). IL-10水平则较正常对照组低(47.3±27.9 mg/L vs 118.3±11.3 mg/L), 差异有显著性(P<0.01). 治疗后肝功能减退组的NO, IL-6, TNF水平较治疗前有显著升高(129.21±27.32 μmol/L vs 92.18±25.68 μmol/L, 198.5±23.2 mg/L vs 147.0±19.1 mg/L, 179.2±23.5 pg/dL vs 121.4±17.5 pg/dL, P<0.05), IL-10水平则明显下降(33.4±7.2 mg/L vs 51.6±18.5 mg/L), 均有差异(P<0.05). 而治疗后肝功能恢复组NO, IL-6, TNF水平较治疗前降低(58.63±12.25 μmol/L vs 94.36±23.45 μmol/L, 90.3±12.7 mg/L vs 148.5±15.8 mg/L, 78.2±14.3 pg/dL vs 124.9±20.1 pg/dL, P<0.05), IL-10水平则明显升高(89.3±18.9 mg/L vs 48.8±9.5 mg/L), 治疗前后有差异(P<0.05).
分组 | n | NO(μmol/L) | IL-6(mg/L) | IL-10(mg/L) | TNF(pg/dL) |
对照组 | 30 | 34.60±10.71 | 71.8±11.4 | 118.3±11.3 | 30.8±14.3 |
肝硬化组 | 56 | 93.80±26.83b | 147.8±26.3b | 47.3±27.9b | 122.6±22.3b |
肝功能减退组 | |||||
治疗前 | 32 | 92.18±25.68 | 147.0±19.1 | 51.6±18.5 | 121.4±17.5 |
治疗后 | 32 | 129.21±27.32c | 198.5±23.2c | 33.4±7.2c | 179.2±23.5c |
肝功能好转或无变化组 | |||||
治疗前 | 24 | 94.36±23.45 | 148.5±15.8 | 48.8±9.5 | 124.9±20.1 |
治疗后 | 24 | 58.63±12.25c | 90.3±12.7c | 89.3±18.9c | 78.2±14.3c |
NO是一种具有多种生物活性的物质, 在体内的生物活性与机体疾病的生理、病理有关, 它参与细胞的信息传递、充当神经递质、介导炎症反应, NO的变化与肝损伤的关系密切[5-6]. 白细胞介素是一组有多种细胞产生的小分子量活性多肽, 在炎症和免疫过程中起重要作用[7], IL-6主要由单核细胞和巨噬细胞产生, 与肝脏局部炎症反应有关, 参与炎性损伤过程, IL-6具有刺激细胞生长, 促进细胞分化和加速肝细胞急性期蛋白合成的作用[8-9]; 在肝纤维化过程中, IL-6水平的升高与肝脏对细胞因子的清除能力下降有关, 而他的产生维持不变[10]. IL-10具有细胞因子合成抑制作用, 是负反馈系统中抑制各种前炎症细胞因子及菌落刺激因子合成的主要因子[11]. IL-10释放增强能抑制早期的炎症反应, 并能对TNF有抑制作用, 有研究表明, IL-10可抑制肝纤维化形成[12]. TNF是由巨噬细胞和激活的淋巴细胞等分泌的细胞因子, 具有广泛的生物活性. Ataseven et al[13]研究了45例乙肝或丁肝病毒感染的肝硬化或肝癌的患者, 证明其血清IL-6, TNF水平显著高于健康人群. Ciecko-Michalska et al[14]分析了24例酒精性肝炎或肝硬化的患者, 发现IL-6, IL-8和TNF高血清表达是预后不良的相关因素.
我们的研究结果表明, 肝硬化患者的NO, IL-6和TNF水平较正常对照组显著升高, IL-10水平则较正常对照组降低, 证实了血清一氧化氮及细胞因子浓度与肝脏损伤有关; 研究结果还发现, 肝硬化患者治疗后肝功能减退组的NO, IL-6和TNF水平较治疗前有显著升高, IL-10水平则明显下降, 反映了肝组织细胞不断受病毒或内毒素刺激后, 肝内单核巨噬细胞系统不断产生大量TNF, 促使细胞因子连续反应, 导致IL- 6产生增加, 同时单核巨噬细胞系统也分泌NO, IL- 6, TNFα和IFN(干扰素), 后者也可促使内皮细胞产生NO, 并在局部发挥其生物学作用, 加重了肝硬化门脉血流动力学的紊乱, 从而单独或共同发挥持续性肝损害作用, 继而导致肝纤维化, 促进肝硬化形成和发展. 肝硬化患者治疗后肝功能好转或无变化组的NO, IL-6, TNF水平较治疗前明显降低, 而IL-10水平则明显升高, 与许多学者研究发现的肝硬化患者血清NO、细胞因子升高与肝硬化严重程度呈正相关的报道相符, 也从侧面证实细胞因子与肝纤维化的程度相关[15]. 我们发现, 经治疗后肝功能好转或无变化组的IL-10水平亦显著升高, 说明IL-10的升高对肝硬化患者的肝功能恢复有利.
总之, 血清NO、细胞因子水平与肝炎后肝硬化严重程度及预后密切相关[16], 可通过检测血清NO及细胞因子水平作为判断肝硬化预后、治疗效果的指标之一.
肝硬化患者的治疗后疗效及预后判断是临床医生非常关注的话题, 已有大量的研究报道. 而通过检测血清NO, 肿瘤坏死因子及细胞因子水平作为判断肝硬化预后、治疗效果的指标方法简便易行.
本文研究了一氧化氮、白介素、肿瘤坏死因子对肝硬化患者预后的影响, 具备一定科学性、创新性和可读性. 但有待于更多例数的进一步证实.
电编:李琪 编辑:王晓瑜
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