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目的观察利多卡因对慢性应激成年小鼠海马齿状回神经元再生的影响及其作用机制。方法将24只重约16～26 g 的成年雄性昆明种小鼠随机分为3个组(n=8):(1)正常对照组(C组):只注射生理盐水不接受应激刺激;(2)单纯慢性应激组(s组):每日注射生理盐水后接受不同应激原的交替刺激;(3)慢性应激复合利多卡因用药组(L 组):每日注射利多卡因后接受不同应激原的交替刺激;反复应激14 d 后注射5-溴脱氧尿嘧啶核苷(BrdU)标记处于分化期的细胞。实验结束时取小鼠肾上腺 HE 染色,并取海马区冰冻切片应用免疫组织化学的方法分别观察不同组小鼠 BrdU 阳性细胞和脑源性神经生长因子(brain-derived neurotrophic factor,BDNF)的情况。结果与 C 组比较,S组小鼠肾上腺皮质排列不整、髓质结构不清;海马齿状回 BrdU 标记的新生细胞及脑源性神经生长因子减少(P<0.05);L 组与 C 组比较差异无统计学意义(P>0.05)。结论成年小鼠海马齿状回存在神经元再生现象,慢性应激可以抑制神经元再生,利多卡因能够阻止这种抑制并可能是通过影响肾上腺皮质功能和脑源性神经生长因子等来促进神经元再生的。
Objective To investigate the effect and mechanism of lidocaine on the regeneration of dentate gyrus neurons in adult hippocampus of chronic stress rats. Methods Twenty-four adult male Kunming mice, weighing about 16-26 g, were randomly divided into three groups (n = 8): (1) normal control group (group C): only physiological saline injection did not receive stress stimulation; (2) Simple chronic stress group (group s): alternating stimulation with different stressors after daily injection of saline; (3) chronic stress with lidocaine group (group L): daily injection of lidocaine After receiving repeated stimulation of different stressors, the cells were treated with BrdU for 14 days. At the end of the experiment, the adrenal glands of the mice were stained with HE, frozen sections of the hippocampus were harvested, and the BrdU positive cells and the brain-derived neurotrophic factor (BDNF) in different groups were observed by immunohistochemistry. Results Compared with group C, the adrenal cortex of mice in group S was not organized and the structure of medulla was unclear. The number of BrdU-labeled neonate cells and brain-derived neurotrophic factor in dentate gyrus of hippocampus were decreased (P <0.05). Compared with group C The difference was not statistically significant (P> 0.05). Conclusion Adult rat hippocampal dentate gyrus regeneration in the phenomenon of neurons, chronic stress can inhibit neuronal regeneration, lidocaine can prevent this inhibition and may be affected by adrenocortical and brain-derived nerve growth factor and other factors to promote nerve Yuan regeneration.