脑出血患者内源性β内啡肽对免疫系统功能的影响(英文)

Effects of endogenous beta-endorphin on the function of immune system of pati ents with cerebral hemorrhage

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。

BACKGROUND:Cerebral hemorrhage(CH) is an extremely serious injury of central n ervous system induced by the mechanism of non pathogenic microorganism infectio n,which surely has very distinct functional activities of nerve endocrine immu noregulation network.Endorphin is an important regulative signal among systems i n the network.It would be helpful for the further comprehension of the mechanism of the nerve endocrine immunoregulation network to explore the changes of end ogenous β endorphin(βend) during the course of the disease and its relationsh ip with the function of immune system,and the effects of exogenous βend on the function of immune active cells cultured in vitro as well,which would provide l aboratorial gist for possible clinical intervention and rehabilitation measure. OBJECTIVE:To investigate the changes of the function of immune system in patie nts with CH and the relationship between endogenous βend and the disease. DESIGN:A case controlled trial. SETTING:Inpatient department of Neurology,Fuxing Hospital, Capital Medical Uni versity;Beijing Red Cross Emergency &Rescue Center;Department of Immunity,Insti tute for Basic Medicine, Peking Union Medical College. PARTICIPANTS:A total of 28 patients with CH visited Beijing Fuxing Hospital an d Red Cross Emergency &Rescue Center from December 2001 to June 2002 were selec ted 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 2 002 were selected in cerebral ischemia control group.Totally 28 subjects visited Peking Union Hospital from February 2002 to June 2002 for physical check up wer e selected in normal control group. INTERVENTIONS:Radioimmunological analysis was used for the detection of serum βend 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 βend on IL 1β,IL 2,IL 8 and iNOS mRNA in PBMC cultur ed in vitro of the patients with CH were analyzed as well. MAIN OUTCOME MEASURES: ①peripheral blood βend content; ②the expressions of cell factors IL 1β,IL 2 and iNOS in peripheral blood mononuclear cell(PBMC); ③the effects of βend(or βend receptor antagonist) on the expression of cell factors IL 1β, IL 2,IL 8 and iNOS in PBMC were observed in vitro. RESULTS:The serum βend 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 patient s 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 isc hemia 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 βend from acute st age to convalescent stage in patients with CH,the difference was not significant .The effective peak range of βend was between 1 ×10-10 and 1 ×10-8 g/L.The expressions of IL 1βand 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 1βfrom acute stage to conva lescent stage,the difference between these two stages was not significant.Howeve r,the elevation of IL 2 was significant. The expressions of IL 1βand IL 2 we re significantly decreased in cerebral ischemia control group compared with norm al control(P< 0.01). The expression of both IL 8 and iNOS in patients with CH i ncreased in acute stage and decreased in convalescent stage, which were signific antly different from that of cerebral ischemia control group and normal control group(P< 0.01), and there was also significant difference between acute stage an d convalescent stage (P< 0.01).The expression of IL 8 of c