GABA能神经元对抗束缚应激后血清淋巴细胞转化抑制因子的产生

ANTAGONISTIC EFFECT OF CEREBRAL GABA-ERGIC SYSTEM ON THE GENERATION OF SERUM SUPPRESSIVE FACTOR(S) INDUCED BY RESTRAINT STRESS IN MICE

我们以前的实验证明,大鼠或小鼠经束缚应激10h后,血清中出现一类淋巴细胞转化抑制因子。它的产生依赖于中枢神经系统的活动。本研究主要观察中枢神经系统中γ-氨基丁酸(GABA)能神经元在应激后血清淋巴细胞转化抑制因子产生中的作用。结果表明,给小鼠腹腔注射 GABA 降解酶抑制剂氨氧乙酸(AOAA,25mg/kg),升高脑内GABA 含量后,几乎完全阻断应激后血清中淋巴细胞转化抑制因子的产生。安定可增强GABA 与 GABA_A 受体的亲和性,给小鼠腹腔注射安定20mg/kg,应激后血清淋巴细胞转化抑制因子的产生也有明显降低。相反,注射 GABA 合成和释放抑制剂3-巯基丙酸(3-MP 24mg/kg),降低脑内GABA能神经元功能,可加强应激后血清淋巴细胞转化抑制因子的产生。以上实验结果从正、反两方面说明应激时脑内GABA能神经元具有对抗血清淋巴细胞转化抑制因子产生的作用。

The involvement of cerebral GABA-ergic system in the generation of the serum suppressive factor(s) was studied in the present work. LACA mice were divided into 4 groups, normal saline (NS) control, NS plus stress, drug control and drug plus stress. The mice in stress groups were restrained in a specially made cylindric cage with hind limbs tied together for 10 hours. The drugs were injected intraperitoneally(i.p.) at the beginning of the stress. Normal mouse lymphocytes were incubated with various dilutions of the serum (1 : 20, 1 : 40 and 1 : 80 or 1 : 10,1 : 20 and 1 : 40) and the lymphocyte proliferation induced by concanavalin (Con A, 0.4μg / well) was observed . The results were as follows: (1) Serum of stress group showed a dramatic inhibitory activity on normal lymphocyte proliferation as compared with NS control group and the inhibitory potency increased gradually with increasing serum concentrations, indicating that a lymphocyte proliferation inhibitory factor(s) was produced in mouse serum by restraint stress. (2) Injection of aminooxyacetic acid (AOAA), an inhibitor of GABA degradation enzyme, before stress resulted in dramatic decrease in the inhibitory activity of the serum on lymphocyte proliferation and increase in cerebral GABA content as compared with NS stress serum (P<0.01). But no significant difference between the AOAA control serum and the NS control serum was observed. (3) Injection of diazepam, which can increase the affinity of GABAA receptor in brain, before stress resulted in significant decrease in suppressive action on lymphocyte proliferation of stress serum as compared with NS stress serum (P<0.05). The diazepam control serum exerted no significant effect on lymphocyte proliferation as NS control serum did. (4) Injection of 3-mercaptopropionic acid (3MP), an inhibitor of the synthesis and release of GABA, before stress reduced GABA content in brain and increased the inhibitory activity of stress serum on lymphocyte proliferation.The above results suggest that GABA-ergic system in brain plays a role in antagonizing the generation of the serum suppressive factor(s) induced by restraint stress.