脑出血患者内源性β内啡肽对免疫系统功能的影响
뇌출혈환자내원성β내배태대면역계통공능적영향
Effects of endogenous beta-endorphin on the function of immune system of pntients with cerebral hemorrhage
  • 万方数据
    中国临床康复 중국림상강복
    CHINESE JOURNAL OF CLINICAL REHABILITATION
    2005年 1期 236-239 ,共4页

    金鑫%赵涵%王俊芳%吴小未%高扬

    금흠%조함%왕준방%오소미%고양

    脑出血%β内啡肽%免疫系统 腦齣血%β內啡肽%免疫繫統
    뇌출혈%β내배태%면역계통
    背景:脑出血是中枢神经系统非病原微生物感染机制致病的极严重的损伤事件,神经-内分泌-免疫系统调节网络的功能活动必然十分明显,内啡肽是调节网络中重要的系统间调节信号,通过探讨疾病过程中内源性β内啡肽水平的变化与免疫系统功能的关系,以及外源性β内啡肽对体外培养的免疫活性细胞功能的影响,能够进一步了解神经内分泌免疫调节网络的作用机制,为可能进行的临床干预治疗及康复措施介入提供实验依据.目的:探讨脑出血患者免疫系统功能的变化及内源性β内啡肽与疾病的关系.设计:病例-对照研究.单位:首都医科大学附属复兴医院神经内科,北京市红十字会急救中心,中国协和医科大学的基础医学研究所免疫室.对象:2001-12/2002-06 北京复兴医院和红十字急救中心就诊的部分脑出血患者28例(脑出血组).2002-02/06 北京复兴医院住院的部分恢复期脑缺血患者28例(脑缺血对照组).2002-02/06 北京协和医院正常体检人群28例(正常对照组).方法:应用放射免疫分析法检测外周血β内啡肽含量;用RT-PCR半定量分析方法检测了外周血单个核细胞白细胞介素(IL)-1β,IL-2,IL-8和一氧化氮合酶(iNOS)mRNA表达;β内啡肽对体外培养的脑出血患者外周血单个核细胞的IL-1β,IL-2,IL-8和iNOS表达的影响.主要观察指标:①外周血β内啡肽含量.②外周血单个核细胞的细胞因子IL-1β,IL-2,IL-8和iNOS表达.③体外观察β内啡肽(或β内啡肽受体拮抗剂)对外周血单个核细胞的细胞因子IL-1β,IL-2,IL-8和iNOS表达的影响.结果:脑出血急性期β内啡肽含量为(115±68)ng/L,恢复期为(160±72)ng/L,正常对照组为(321±62)ng/L,脑缺血对照组为(264±163)ng/L.正常对照组和脑缺血对照组与急性期比较,差异有显著性意义(t=11.84,t=4.46,P＜0.01);脑出血恢复期与脑缺血对照组和正常对照组比较,差异有显著性意义(t=3.09,P＜0.05;t=8.96,P＜0.01).脑出血患者恢复期β内啡肽含量与急性期比较呈上升趋势,但无统计学意义.β内啡肽作用峰值的浓度为1×10-10～1×10-8g/L.脑出血急性期和恢复期患者IL-1β,IL-2表达均显著低于脑缺血对照组和正常对照组(P＜0.01);急性期与恢复期比较,IL-1β呈上升趋势,但无统计学意义,IL-2升高明显;脑缺血对照组与正常对照组比较,呈显著下降(P＜0.01).脑出血患者IL-8,iNOS的表达均呈现急性期增高,恢复期下降的结果,与脑缺血对照组和正常对照组比较差异有显著性意义(P＜0.01);急性期与恢复期比较差异有显著性意义(P＜0.01);脑缺血对照组与正常对照组比较,IL-8呈显著下降(P＜0.05),iNOS无统计学意义(P＞0.05).结论:脑出血患者内源性β内啡肽水平呈持续低下状态;免疫系统功能变化为先升后降,功能低下呈持续状态;外源性β内啡肽可增强脑出血患者外周血单个核细胞IL-1β,IL-2,IL-8和iNOS的表达,β内啡肽受体拮抗剂纳络酮可阻断β内啡肽的正向免疫调节作用.
    배경:뇌출혈시중추신경계통비병원미생물감염궤제치병적겁엄중적손상사건,신경-내분비-면역계통조절망락적공능활동필연십분명현,내배태시조절망락중중요적계통간조절신호,통과탐토질병과정중내원성β내배태수평적변화여면역계통공능적관계,이급외원성β내배태대체외배양적면역활성세포공능적영향,능구진일보료해신경내분비면역조절망락적작용궤제,위가능진행적림상간예치료급강복조시개입제공실험의거.목적:탐토뇌출혈환자면역계통공능적변화급내원성β내배태여질병적관계.설계:병례-대조연구.단위:수도의과대학부속복흥의원신경내과,북경시홍십자회급구중심,중국협화의과대학적기출의학연구소면역실.대상:2001-12/2002-06 북경복흥의원화홍십자급구중심취진적부분뇌출혈환자28례(뇌출혈조).2002-02/06 북경복흥의원주원적부분회복기뇌결혈환자28례(뇌결혈대조조).2002-02/06 북경협화의원정상체검인군28례(정상대조조).방법:응용방사면역분석법검측외주혈β내배태함량;용RT-PCR반정량분석방법검측료외주혈단개핵세포백세포개소(IL)-1β,IL-2,IL-8화일양화담합매(iNOS)mRNA표체;β내배태대체외배양적뇌출혈환자외주혈단개핵세포적IL-1β,IL-2,IL-8화iNOS표체적영향.주요관찰지표:①외주혈β내배태함량.②외주혈단개핵세포적세포인자IL-1β,IL-2,IL-8화iNOS표체.③체외관찰β내배태(혹β내배태수체길항제)대외주혈단개핵세포적세포인자IL-1β,IL-2,IL-8화iNOS표체적영향.결과:뇌출혈급성기β내배태함량위(115±68)ng/L,회복기위(160±72)ng/L,정상대조조위(321±62)ng/L,뇌결혈대조조위(264±163)ng/L.정상대조조화뇌결혈대조조여급성기비교,차이유현저성의의(t=11.84,t=4.46,P＜0.01);뇌출혈회복기여뇌결혈대조조화정상대조조비교,차이유현저성의의(t=3.09,P＜0.05;t=8.96,P＜0.01).뇌출혈환자회복기β내배태함량여급성기비교정상승추세,단무통계학의의.β내배태작용봉치적농도위1×10-10～1×10-8g/L.뇌출혈급성기화회복기환자IL-1β,IL-2표체균현저저우뇌결혈대조조화정상대조조(P＜0.01);급성기여회복기비교,IL-1β정상승추세,단무통계학의의,IL-2승고명현;뇌결혈대조조여정상대조조비교,정현저하강(P＜0.01).뇌출혈환자IL-8,iNOS적표체균정현급성기증고,회복기하강적결과,여뇌결혈대조조화정상대조조비교차이유현저성의의(P＜0.01);급성기여회복기비교차이유현저성의의(P＜0.01);뇌결혈대조조여정상대조조비교,IL-8정현저하강(P＜0.05),iNOS무통계학의의(P＞0.05).결론:뇌출혈환자내원성β내배태수평정지속저하상태;면역계통공능변화위선승후강,공능저하정지속상태;외원성β내배태가증강뇌출혈환자외주혈단개핵세포IL-1β,IL-2,IL-8화iNOS적표체,β내배태수체길항제납락동가조단β내배태적정향면역조절작용.
    BACKGROUND: Cerebral hemorrhage(CH) is an extremely serious injury of central nervous system induced by the mechanism of non-pathogenic microorganism infection, which surely has very distinct functional activities of nerve-endocrine-immunoregulation network. Endorphin is an important regulative signal among systems in the network. It would be helpful for the further comprehension of the mechanism of the nerve- endocrine-immunoregulation network to explore the changes of endogenousβ-endorphin (β end) during the course of the disease and its relationship with the function of immune system, and the effects of exogenous β end on the function of immune-active cells cultured in vitro as well, which would provide laboratorial gist for possible clinical intervention and rehabilitation measure.OBJECTIVE: To investigate the changes of the function of immune system in patients with CH and the relationship between endogenous β end and the disease.DESIGN: A case-controlled trial.SETTING: Inpatient department of Neurology, Fuxing Hospital, Capital Medical University; Beijing Red Cross Emergency & Rescue Center;, Department of Immunity, Institute for Basic Medicine, Peking Union Medical College.PARTICIPANTS: A total of 28 patients with CH visited Beijing Fuxing Hospital and Red Cross Emergency & Rescue Center from December 2001 to June 2002 were selected in CH group. And 28 patients with CH in their convalescent stage admitted by the inpatient department of Beijing Fuxing Hospital from February 2002 to June 2002 were selected in cerebral ischemia control group. Totally 28 subjects visited Peking Union Hospital from February 2002 to June 2002 for physical check up were selected in normal control group.INTERVENTIONS: Radioimmunological analysis was used for the detection of serum β end concentration in peripheral blood. RT-PCR half-quantitative analysis was used for the expressions of Interleukin (IL) -1β, IL-2, IL-8 and iNOS mRNA in PBMC. The effects of β end on IL-1β, IL-2, IL-8 and iNOS mRNA in PBMC cultured in vitro of the patients with CH were analyzed as well.the expressions of cell factors IL-1β, IL-2 and iNOS in peripheral blood onist) on the expression of cell factors IL-1β, IL-2, IL-8 and iNOS in PBMC were observed in vitro.RESULTS: The serum β end level of the patients with CH was(115 ± 68) ng/L at the acute stage and(160 ± 72) ng/L at convalescent stage; while the level was(321 ± 62) ng/L in the subjects of normal control group and(264 ± 163) ng/L in the patients of cerebral ischemia control group. The difference between normal control group, cerebral ischemia control group,and CH acute stage were significant( t = 11.84, t =4.46, P.＜ 0.01), and the differences between CH convalescent stage and cerebral ischemia control group, normal control group were significant as well( t = 3.09, P ＜ 0.05;t = 8.96, P ＜ 0. 01 ) . Although there was an ascending tendency in β end from acute stage to convalescent stage in patients with CH, the difference was not significant. The effective peak range of β end was between 1 × 10-10 and 1× 10-8 g/L. The expressions of IL-1β and IL-2 in both acute and convalescent patients with CH were significantly lower than that of CH control and normal control groups( P ＜ 0.01) . Although there was an ascending tendency in IL-1β from acute stage to convalescent stage, the difference between these two stages was not significant. However, the elevation of IL-2 was significant. The expressions of IL-1β and IL-2 were significantly decreased in cerebral ischemia control group compared with normal control( P ＜ 0.01 ).The expression of both IL-8 and iNOS in patients with CH increased in acute stage and decreased in convalescent stage, which were significantly different from that of cerebral ischemia control group and normal control group( P ＜ 0. 01 ), and there was also significant difference between acute stage and convalescent stage ( P ＜ 0. 01 ). The expression of IL-8 of cerebral ischemia control group significantly decreased compared with that of normal control group ( P ＜ 0. 05), while there was no significant different in the expression of iNOS between these two groups ( P ＞ 0. 05).CONCLUSION: The endogenous β end level of CH patients is a persistent low status. The function of immune system is up-regulated first and then down-regulated, which is in persistent low status as well. Exogenous β end enhances the expressions of IL-1β,IL-2,IL-8 and iNOS mRNA in PBMC. βend receptor antagonist, Naloxone, can block the positive immunoregulation of β end.
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