低剂量氢化可的松治疗感染性休克时对外周血T淋巴细胞凋亡的影响及机制
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Effect and mechanism of low dose hydrocortisone on circulating lymphocyte apoptosis in human septic shock
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    摘要:

    目的:探讨低剂量氢化可的松治疗感染性休克时对外周血T淋巴细胞凋亡的影响及机制-方法:前瞻性的将南京市第一医院ICU自2006年1月~2009年1月收治的57例感染性休克患者按照随机对照的原则分为低剂量氢化可的松治疗组和对照组,同时选择20例健康志愿者和18例脓毒血症患者-采取外周血,用Annexin V法和流式细胞仪测定T淋巴细胞亚群的凋亡情况,用酶增敏免疫测定(EASIA)法测定血清中肿瘤坏死因子α(TNF-α)-白细胞介素-1β(IL-1β)-白细胞介素-10(IL-10)的浓度,观察低剂量氢化可的松对上述各项指标的影响-结果:在初始状态下,外周血CD4+ T淋巴细胞亚群的凋亡在健康对照组-脓毒血症组及感染性休克组分别为(4.41±1.45)%,(7.87±3.82)%及(11.01±4.52)%,感染性休克患者的外周血CD4+ T淋巴细胞亚群的凋亡多于脓毒血症患者(P < 0.05),脓毒血症患者多于健康对照组(P < 0.05);而初始状态下健康对照组-脓毒血症组及感染性休克组患者外周血T淋巴细胞CD8+亚群的凋亡,3组比较差异无统计学意义(P > 0.05)-48 h后休克对照组和治疗组CD4+亚群的凋亡分别为(19.39±6.63)%和(22.61±5.64)%,治疗组明显多于对照组(P < 0.05);而48 h后CD8+亚群的凋亡为在休克对照组和治疗组之间比较无统计学意义(P > 0.05)-在基础状态下TNF-α的浓度在健康对照组,脓毒血症组及感染性休克组中分别为(16.44±9.55)pg/mL,(29.58±13.6)pg/mL及(47.99±25.63)pg/mL,感染性休克组高于脓毒血症组(P < 0.05),脓毒血症组高于健康对照组(P < 0.05),持续72 h;起病48 h后感染性休克对照组和治疗组的TNF-α浓度分别为(73.47±25.39)pg/mL和(59.66±16.37)pg/mL,治疗组明显低于对照组(P < 0.05);IL-1β在健康对照组-脓毒血症组及感染性休克组中分别为(13.12±5.07)pg/mL,(25.21±14.7)pg/mL及(22.94±22.01)pg/mL,感染性休克组和脓毒血症组的浓度均高于健康对照组(P < 0.05),但是感染性休克组和脓毒血症组的浓度差异无统计学意义(P > 0.05),发病48 h后感染性休克对照组和治疗组的IL-1β的浓度比较没有差异(P > 0.05)-基础状态下IL-10的浓度在健康对照组,脓毒血症组及感染性休克组中分别为(6.38±7.5)pg/mL,(9.67±4.88)pg/mL及(15.01±5.36)pg/mL,感染性休克组中的IL-10的浓度高于脓毒血症组(P < 0.05),脓毒血症组高于健康对照组(P < 0.05),持续72 h;发病48 h后,休克对照组的IL-10的浓度为(30.18±16.62)pg/mL,治疗组为(40.62±24.23)pg/mL,治疗组的浓度要高于对照组(P < 0.05)-结论:采用低剂量氢化可的松治疗感染性休克时,可以使CD4+淋巴细胞凋亡明显增多,同时会使IL-10升高,IL-10升高可能是氢化可的松治疗感染性休克时诱导外周血CD4+T淋巴细胞凋亡增多的原因之一-

    Abstract:

    Objective:To investigate the effect and mechanism of hydrocortisone on circulating T lymphocyte apoptosis in human septic shock. Methods:Total 57 patients with septic shock from January 2006 to January 2009 in Intensive Care Unit of Nanjing First Hospital Affiliated to NJMU were prospectively randomized into treatment groups and control group. Low-dose hydrocortisone was used in treatment group but not in control group. Peripheral venous blood samples of the included patients were obtained to determine the circulating T lymphocyte apoptosis by Annexin V and flow cytometry. At the meantime,the plasma concentration of TNF-α,IL-1β and IL-10 were determined by EASIA. All these results were compared with 20 healthy volunteers and 18 pyemia patients. In the meantime,the difference of septic shock control group and hydrocortisone treatment group was analyzed to investigate the effect of low-dose hydrocortisone on these results. Results:In baseline,the apoptosis percentage of CD4+T lymphocytes in healthy volunteers,pyemia patients and septic shock patients was (4.41±1.45)%,(7.87±3.82)% and (11.01±4.52)%,respectively. And the percentage of Annexin V-positive CD4+ T lymphocytes was higher in septic shock patients than in pyemia patients(P < 0.05),and the later was higher than healthy volunteers(P < 0.05). At the same time, there was no difference in the apoptosis percentage of CD8+ T lymphocytes among these groups(P > 0.05). After treatment of 48 h,the apoptosis percentage of CD4+ T lymphocytes was higher in hydrocortisone treatment group than that in control group,(P < 0.05),while,the apoptosis percentage of CD8+ T lymphocytes had no difference between the two groups(P > 0.05). The plasma concentration of TNF-α in healthy volunteers,pyemia patients and and septic shock patients in baseline was (16.44±9.55)pg/mL,(29.58±13.6)pg/mL and (47.99±25.63) pg/mL respectively. And it was higher in septic shock patients than in pyemia patients(P < 0.05). And the later was higher than healthy volunteers(P < 0.05). After treatment of 48 hours,the plasma concentradtion of TNF-α in hydrocortisone treatment group was lower than that in control group(P < 0.05). The plasma concentration of IL-1β in healthy volunteers,pyemia patients and septic shock patients in baseline was (13.12±5.07)pg/mL,(25.21±14.7)pg/mL and (22.94±22.01)pg/mL respectively. It was higher in pyemia patients and septic shock patients than that in healthy volunteers(P < 0.05). However,there was no difference between the pyemia patients and septic shock patients.(P > 0.05). After treatment of 48 hours,Threr was no difference in the plasma concentration of IL-1β between control group and hydrocortisone treatment group(P > 0.05). The plasma concentration of IL-10 in healthy volunteers,pyemia patients and and septic shock in baseline was(6.38±7.5) pg/mL,(9.67±4.88)pg/mL and(15.01±5.36) pg/mL respectively. It was higher in septic shock than in pyemia patients (P < 0.05). And the later was higher than healthy volunteers(P < 0.05). Forty-eight hours after onset,the plasma concentration of IL-10 in hydrocortisone treatment group was higher than that in control group(P < 0.05). Conclusion:Low-dose hydrocortisone can induce CD4+ T lymphocytes apoptosis when administered in septic shock,and it can also up-regulate the plasma concentration of IL-10. We concluded that IL-10 may be one of the reasons that low-dose hydrocortisone induced circulating CD4+ T lymphocytes apoptosis in septic shock.

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李秀华,陈永铭,洪 亮,袁受涛,郑曙云.低剂量氢化可的松治疗感染性休克时对外周血T淋巴细胞凋亡的影响及机制[J].南京医科大学学报(自然科学版),2011,(5):730-735

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  • 收稿日期:2010-12-21
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