β内啡肽对脑出血患者免疫系统功能的影响

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

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。

Objective To study the influence of β-endorphin (β end)on the function of immune system of patients with cerebral hemorrhage at different stages. Methods Radioimmunal analysis was applied to detect the serum β-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. Monunuclear cells from peripheral blood of these 3 kinds of subjects were cultured and then β end 10 -8 g/L, β end 10 -11 g/L, β end 10 -14 g/L,or β 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 (β end 10 -8 g/L group, β end 10 -11 g/L group, β end 10 -14 g/L group,and β end 10 -11 g/L + Nal group). Another MNCs were cultured without addition of β end (β end 0 g/L group). Then the MNCs were collected. RT-PCR was used to detect the expressions of interleukin (IL)-1β,IL-2, IL-8 and iNOS mRNA in the MNCs. Results The serum β-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-1β 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-1β 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-1β,IL-2, IL-8, and iNOS mRNA in the peripheral blood MNCs in vitro in the β end 10 -8 g/L group and β end 10 -11 g/L group were significantly higher than those of the β end 0 g/L group, β end 10 -11 g/L group, and β-end 10 -11 g/L +Nal 10 -5 g/L group. The expressions of IL-1β,IL-2, IL-8, and iNOS mRNA in the peripheral blood MNCs in the β-end 10 -11 g/L +Nal 10 -5 g/L group were higher than those of the β end 0 g/L group, however, not significantly. Conclusions The endogenous β-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 β-endorphin enhances the IL-1 β,IL-2,IL-8 and iNOS mRNA expression of peripheral blood MNCS. β-endorphin receptor antagonist naloxone blocks the positive immunoregulation by β-endorphin.