杏仁核脑区硫化氢对创伤后应激障碍模型大鼠抑郁样行为的影响

目的:探讨创伤后应激障碍(posttraumatic stress disorder,PTSD)大鼠抑郁样行为改变及杏仁核内胱硫醚β-合成酶(cystathionineβ-synthase,CBS)/硫化氢(hydrogen sulfide,H_2S)水平的变化,并研究补充H_2S对大鼠抑郁样行为的作用及机制。方法:应用连续单一应激方案制备PTSD动物模型,用强迫游泳实验和糖水偏好实验检测大鼠抑郁样行为,用Western blot技术和亚甲基蓝法检测杏仁核CBS/H_2S体系含量,用整体细胞外电生理方法记录杏仁核神经元放电情况。结果:与正常对照组比较,PTSD组大鼠强迫游泳不动时间显著延长(P0.01),糖水偏好率显著降低(P0.01);杏仁核脑区的CBS/H_2S体系含量显著降低(P0.01)。与PTSD组比较,PTSD+硫氢化钠组大鼠强迫游泳不动时间显著减少(P0.01),糖水偏好率显著升高(P0.01)。微量压力注射L-半胱氨酸使杏仁核神经元自发放电频率显著升高(P0.01)。结论:PTSD大鼠通过抑制杏仁核CBS/H_2S体系导致抑郁样行为加重。H_2S拮抗PTSD大鼠抑郁样行为的机制可能与其增加杏仁核神经元放电频率和兴奋性有关。

Effect of amygdala H2S system on depression-like behavior in posttraumatic stress disorder rats

AIM: To explore the depression-like behavior and cystathionine β-synthase (CBS)/hydrogen sulfide (H₂S) levels of amygdala in posttraumatic stress disorder (PTSD) rats and to study the effect of exogenous H₂S on PTSD rats.METHODS: Single prolonged stress paradigm was adopted to prepare PTSD animal model. Forced swimming test and sucrose preference test were used to evaluate the depression-like behavior. The content of CBS/H₂S in amygdala tissue was measured by Western blot and methylene blue method. In vivo extracellular single unit recordings was used to examine the frequency of spontaneous discharges of amygdala neurons.RESULTS: The immobility time in forced swimming test of PTSD group increased and sucrose preference in sucrose preference test of PTSD group decreased compare with normal group (P<0.01). CBS/H₂S level in amygdala tissue of PTSD group decreased compared with normal group (P<0.01). The immobility time of the rats in forced swimming test of NaHS+PTSD group decreased and the sucrose prefe-rence in sucrose preference test of NaHS+PTSD group increased compare with PTSD group (P<0.01). L-cysteine increased the frequency of spontaneous discharges of amygdala neurons (P<0.01).CONCLUSION: Depression-like behavior is aggravated in PTSD model rats owing to the inhibition of CBS/H₂S content in amygdala tissue. The mechanism of behavior-improving effect of H₂S on PTSD model rats is possibly related to excitating amygdala neurons and increasing the frequency of spontaneous discharges.