H2S拮抗皮质醇诱导的大鼠抑郁症模型海马神经元及突触损伤  

Hydrogen sulfide antagonizes corticosterone-induced neurons and synapses damages in the hippocampus of depression rat models

作　　者：张平[1] 蒋莉[1] 刘稀金[1] 曹琳[1] 陈勇军[1] Zhang Ping Jiang Li Liu Xijin Cao Lin Chen Yongiun(Department of Neurology, Nanhua Hospital Affiliated to South China University, Hengyang 421001, China)

机构地区：[1]南华大学附属南华医院神经内科,衡阳421001

出　　处：《中华神经医学杂志》2017年第10期1034-1040,共7页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金（81471310）;衡阳市科技局课题（2012KJ62）

摘　　要：目的探讨硫化氢（H2S）对皮质醇（CORT）诱导的大鼠抑郁症模型海马神经元及突触损伤的影响。方法雄性SD大鼠按随机数字表法分为4组：对照组、CORT组、低浓度硫氢化钠（NaHS）（30 μmol/kg）处理组、高浓度NaHS（100 μmol/kg）处理组，每组10只。后3组大鼠持续经皮下注射CORT（40 mg/kg） 28 d建立大鼠抑郁症模型。CORT干预第15天起，CORT组和对照组给予生理盐水（5 mL/kg）腹腔注射，低浓度NaHS处理组、高浓度NaHS处理组分别给予NaHS（30、100 μmol/kg）腹腔注射，均持续14 d。采用蔗糖偏好实验评估各组大鼠的抑郁样行为，采用HE染色观察海马CA3区细胞病理改变，采用TUNEL染色观察海马CA3区细胞凋亡情况，采用Western blotting检测海马组织中Bax、Bcl-2及突触素（Syn）蛋白表达，采用ELISA法检测海马组织中Caspase-3活性。结果与对照组相比，CORT组大鼠蔗糖偏好指数明显下降，海马CA3区细胞排列紊乱且较多细胞出现核固缩改变，凋亡细胞相对比值明显增高，Bcl-2及Syn蛋白表达水平明显降低，Bax蛋白表达水平及Caspase-3活性明显增高，差异均有统计学意义（P〈0.05）。与CORT组相比，低浓度NaHS处理组、高浓度NaHS处理组大鼠蔗糖偏好指数均明显增高，海马CA3区细胞形态结构均明显改善，凋亡细胞相对比值均明显降低，Bcl-2及Syn蛋白表达水平均明显增高，Bax蛋白表达水平及Caspase活性均明显降低，差异均有统计学意义（P〈0.05）；但低浓度NaHS处理组与高浓度NaHS处理组之间上述指标比较差异均无统计学意义（P〉0.05）。结论H2S可有效拮抗CORT诱导的大鼠抑郁症模型海马神经元及突触损伤。Objective To explore the effect of hydrogen sulfide （H：S） on corticosterone （CORT） -induced neuronal and synaptic damages in the hippocampus of depression rat models. Methods Adult male SD rats were randomly divided into 4 groups： control group, CORT group, low-concentration NariS （30 μmol/kg） treatment group and high-concentration NailS （100 μmol/kg） treatment group （n=10）. CORT （40 mg/kg） was subcutaneously injected into the rats from the later three groups for 28 d to establish depression models. After administration of CORT for 14 d, the control rats and CORT rats were treated with normal saline （5 mL/kg, ip） for 14 d, rats in the later two groups were treated with NariS （30 and 100 μmol/kg/d, ip） for 14 d. The depressive-like behaviors were evaluated by sucrose preference test, the neuronal pathological changes in the hippocampus CA3 area were observed by HE staining, the neuronal apoptosis in the hippocampus was observed under microscope using Tunel staining, the protein expressions of Bcl-2, Bax and synaptophysin in the hippocampus were quantified by Western blotting, and the content of Caspase-3 was analyzed by ELISA. Results After administration of CORT for 28 d, rats from the CORT group exhibited decreased sucrose preference, disordered arrangement and sparse morphology as well as increased amount of apoptotic neuron in hippocampal CA3 area as compared with those in the control group with significant differences （P〈0.05）; in addition, as compared with those in the control group, the expressions of Bcl-2 and SYN in the hippocampus were significantly suppressed, while the activity of Caspase-3 and the expression of Bax in hippocampus were significantly up-regulated in the rats from the CORT group （P〈0.05）. As compared with CORT group, low-concentration NariS treatment group and high-concentration NariS treatment group had significantly increased sucrose preference, improved arrangement of neurons, decreased amount of apoptotic neurons in CA3 areas of CORT

关 键 词：抑郁症 硫化氢 皮质酮 海马 神经元 突触 

分 类 号：R-332[医药卫生] R749.4