以前的研究发现情绪应激可明显减少特异性抗卵清蛋白(ovalbumin, OVA)抗体的产生，并激活下丘脑一垂体一肾上腺轴(hypothalamic-pituitary-adrenal,HPA )和交感神经系统(sympathetic nervous system, SNS)，导致血浆中皮质酮( corticosterone,CORT)和去甲肾上腺素(norepinephrine,NE)水平升高。研究还发现NE的升高与抗体水平呈明显负相关，提示应激诱发的体液免疫抑制可能与SNS有关。为了进一步澄清HPA轴与SNS在应激免疫调节中的作用和参与的受体类型，本文采用药物学方法，以血清抗OVA抗体水平作为体液免疫功能指标，研究应激不同阶段对大鼠体液免疫反应的影响及其调节机制。研究包括如下
第二部分研究了慢性应激停止后对大鼠体液免疫反应的长期影响及其可能的机制。动物经历了2周或4周情绪应激后，停止应激，经过不同的恢复期((1天或7天)，用牛血清白蛋白(bovine serum albumin, BSA)免疫大鼠。动态观察免疫后14, 21和28天血清抗BSA抗体水平;进一步通过情绪应激前心得安阻断，观察应激过程中SNS激活在应激影响免疫的后效应形成中可能的作用。结果如下:
Our previous work demonstrated that chronic stress activated both the hypothalamic-pituitary-adrenal axis (HPA) and the sympathetic nervous system (SNS) (increased the level of corticosterone and norepinephrine in blood，significantly suppressed the level of specific anti-ovalbumine(OVA) IgG antibody production in rats. A negative correlation between antibody and norepinephrine levels was also found, suggesting that sympathetic nervous system may be involved in the stress-induced immunomosuppre}sion. To further clarify the role of HPA axis and SNS and the involvement of receptor types in stress-induced immunosuppression, using pharmalogical approaches, the present study investigated the dynamic alterations of humoral immunity in rats during different periods of stress, as well as possible mechanisms. Experiments are divided into two parts.
In the first part, by respectively pretreating rats with the CORT synthesis inhibitor metyrapone and the chemical sympathectomy drug 6-hydroxydopamine to abrogate the role of corticosterone and NE, with the nonselectivep-ADR antagonist propranolol and selective p1-ADR antagonist atenolol and the selective }i2-ADR antagonist ICI118, 551 to block corresponding type/subtype of adrenergic receptors; the mechanisms underlying the decrease of anti-OVA antibody production induced by stress were investigeted. Results are as follows:
1 Intraperitoneal injection of 6-OHDA but not metyrapone completely blocked the stress suppressive effects on anti-OVA antibody production, suggesting that peripheral SNS postganglionic neurotransmitter NE plays a major role in the stress-induced humoral immunosuppression.
2 Propranolol reversed the stress-induced humoral immunosuppression in a dose-dependent manner, suggesting that (3-ADR mediated this immunomodulation.
3 The selective }i2-ADR antagonist ICI118, 551 but not selective [31-ADR antagonist atenolol significantly increased antibody production in stressed rat to normal level.
In the second part, experime-}ts were performed to study the prolonged change of humoral immunoreactivity and its association with basal SNS reactivity (determined by basal NE concentration in plasma) after cessation of chronic stress. Rats were submitted to 2 or 4 weeks chronic stress. All rats were immunized by ip BSA at 1 or 7 days after cessation of stress, and the anti-BSA antibody level was determined at 14,21 and 28 days after immunization. Furthermore, the effects of blockadep-ADR activation by propranolol pretreatment before every stress episode on the immunomodulation post cessation of stress were also studied. Results are as follows:
1 Immunized at 1 day but not 7 days after cessation of 2-week stress, anti-BSA antibody level in previously stressed rats significantly decreased than that of controls.On the contrary, antibody level of rat experienced 4-week stress paradigm significantly lower than that of control group at both 1 day and 7 days after cessation of stress. These results showed that humoral immunity of rat was still inhibited after chronic stress schedule.
2 Propranolol pretreatment restored the decrease of antibody level in previously stressed rats, suggesting thatp-ADR was involved in forming of long-lasting immune changes after chronic stress.
In summary, these results indicate that there exists inhibitory alteration of humoral immunity in rats during different periods of chronic stress(during and post cessation of chronic stress). SNS plays an important role in the humoral immunosuppression during chronic stress via p2-ADR. After cessation of chronic stress, prolonged alteration of humoral immunosuppression was also observed. Blockade of propranolol reversed this effect, suggestding (3-ADR involved in the forming of stress-induce post-effects on humoral immunity in rats.