β内啡肽对脑出血患者免疫系统功能的影响

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。 方法　应用放射免疫分析法检测 2 8例脑出血患者及 5 6例对照组 (脑缺血患者及正常人群 )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。结果　脑出血急性期 β内啡肽含量为 115ng/L± 6 8ng/L ,正常对照组为 32 1ng/L± 6 2ng/L (P <0 0 1) ,脑缺血对照组为 2 6 4ng/L± 16 3ng/L(P <0 .0 5 )。β内啡肽可增强体外培养的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内啡肽作用峰值的浓度为 10 -8～ 10 -11g/L ;β内啡肽的增强作用可被受体拮抗剂纳络酮阻断。 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。

Influence of beta-endorphin on function of immune system of patients with cerebral hemorrhage

OBJECTIVE: To study the influence of beta-endorphin (beta end) on the function of immune system of patients with cerebral hemorrhage at different stages. METHODS: Radioimmunal analysis was applied to detect the serum beta-endorphin concentration in the peripheral blood of 28 patients with cerebral hemorrhage, aged 65.5 +/- 13, 28 age-matched patients with cerebral thrombosis, and 28 sex and age-matched normal controls. Mononuclear cells from peripheral blood of these 3 kinds of subjects were cultured and then beta end 10(-8) g/L, beta end 10(-11) g/L, beta end 10(-14) g/L, or beta end 10(-11) g/L + naloxone 10(-5) g/L were added into the media respectively and the MNCs were cultured for more 24 hours (beta end 10(-8) g/L group, beta end 10(-11) g/L group, beta end 10(-14) g/L group, and beta end 10(-11) g/L + Nal group). Another MNCs were cultured without addition of beta end (beta end 0 g/L group). Then the MNCs were collected. RT-PCR was used to detect the expressions of interleukin (IL)-1beta, IL-2, IL-8 and iNOS mRNA in the MNCs. RESULTS: The serum beta-end level of the patients with cerebral hemorrhage at the acute stage was 129 +/- 82 ng/L, significantly lower than that of the normal controls (321 +/- 62 ng/L, P<0.01) and that of the patients with cerebral thrombosis (264 +/- 163 ng/L, P<0.05), but not significantly different from that of the patients with cerebral hemorrhage in the convalescent stage (160 +/- 72 ng/L, P>0.05). The expression of IL-1beta and the expression of IL-2 of the patients with cerebral hemorrhage at the acute stage were significantly lower than those of the patients with cerebral thrombosis and the controls (all P<0.01). The expression of IL-1beta of the patients with cerebral hemorrhage at the convalescent stage were higher than that in the acute stage, however, the difference was not significant (P>0.05). The expression of IL-2 of the patients with cerebral hemorrhage at the convalescent stage was higher than that at the acute stage (P<0.01). The expression of IL-8 and the expression of iNOS of the patients with cerebral hemorrhage at the acute stage were significantly higher than those of the patients of cerebral thrombosis and the controls (both P<0.01). The expression of IL-8 and the expression of iNOS of the patients with cerebral hemorrhage at the convalescent stage were significantly lower than those in the acute stage (both P<0.01). The expressions of IL-1beta, IL-2, IL-8, and iNOS mRNA in the peripheral blood MNCs in vitro in the beta end 10(-8) g/L group and beta end 10(-11) g/L group were significantly higher than those of the beta end 0 g/L group, beta end 10(-11) g/L group, and beta-end 10(-11) g/L + Nal 10(-5)g/L group. The expressions of IL-1beta, IL-2, IL-8, and iNOS mRNA in the peripheral blood MNCs in the beta-end 10(-11) g/L +Nal 10(-5) g/L group were higher than those of the beta end 0 g/L group, however, not significantly. CONCLUSIONS: The endogenous beta-endorphin level of cerebral hemorrhage patients is low. The immune system function is up-regulated at the acute stage and then down-regulated. Thereafter the immune system function is invariably low. Exogenous beta-endorphin enhances the IL-1 beta, IL-2, IL-8 and iNOS mRNA expression of peripheral blood MNCS. beta-endorphin receptor antagonist naloxone blocks the positive immunoregulation by beta-endorphin.