硫化氢对慢性应激致大鼠海马神经损伤的保护作用及机制  

Protective effects of hydrogen sulfide on chronic stress-induced hippocampal neural injury in rats and its mechanisms

作　　者：蒋莉[1] 张平[1] 罗焱[1] 李文婷[1] 毕丽丽[1] 邹伟[1] 

机构地区：[1]南华大学附属南华医院神经内科,衡阳421002

出　　处：《中华行为医学与脑科学杂志》2016年第1期19-23,共5页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金（81471310）;衡阳市科技局课题（2012KJ62）;湖南省研究生科研创新项目（CX2015B423）

摘　　要：目的 探讨硫化氢（H2S）对大鼠慢性非预期温和应激模型（chronic unpredictable mild stress,CUMS）海马神经损伤的保护作用及机制.方法 将40只SD雄性大鼠随机分为对照组、CUMS组、CUMS＋低浓度NaHS（1.68 mg/kg×14 d,ip）组、CUMS＋高浓度NaHS组（5.6 mg/kg× 14 d,ip）,4周后CUMS模型建立取大鼠海马组织,HE染色观察海马CA3区细胞排列情况及细胞形态,Tunel染色检测海马区神经细胞凋亡,Elisa法测海马组织klotho蛋白表达,亚甲基蓝分光光度计法检验海马组织内源性H2S含量,免疫组化检测大鼠海马神经元再生.结果 CUMS组大鼠海马CA3区神经细胞排列稀疏、紊乱,DG区神经发生明显被抑制,凋亡细胞相对比值（1.151±0.041）较对照组明显增加（P＜0.01）,klotho蛋白相对表达量（0.910±0.032）及内源性H2S的生成能力[（0.445±0.025）nmol· mg-1·min-1]较对照组Klotho蛋白相对表达量及内源性H2S生成能力[（0.621 ±0.019）nmol·mg-1·min-1]明显减少（均P＜0.05）.NaHS低、高浓度组大鼠海马CA3区神经细胞结构及DG区神经元数量发生明显改善,凋亡细胞相对比值[（1.032±0.023）、（1.045±0.038）]较CUMS组明显较少（P＜0.01）,Klotho蛋白相对表达量[（1.045±0.021）、（1.046±0.076）]及内源性H2S生成能力[（0.582±0.008）、（0.585±0.029） nmol·mg-1·min-1]较CUMS组明显增加（均P＜0.05）.结论 硫化氢可能通过上调Klotho蛋白、促进内源性H2S生成和神经发生而拮抗慢性应激导致的海马神经损伤.Objective To investigate the protective effect of hydrogen sulfide （H2S） on chronic unpredictable mild stress （CUMS）-induced damage in hippocampus of rats and explore potential mechanisms.Methods 40 SD rats were divided into four groups,including controI,CUMS,CUMS co-treated with NaHS （1.68 mg/kg×14 d,ip） and CUMS co-treated with NaHS （5.6 mg/kg×14 d,ip） groups.After treatment with CUMS for 4 weeks,arrangement and morphology of hippocampal neuron were examined by HE staining,apoptosis of hippocampal neurons were measured by Tunel assay.Klotho expression was detected by ELISA.Meanwhile,the generation of H2S in the hippocampus was measured by spectrophotometry and the neurogenesis of hippocampus was detected by Brdu staining.Results The arrangement and morphology of CA3 hippocampal cells were disturbed and the neurogenesis in hippocampal DG region were inhibited in the CUMS group compared with control group.Moreover,the CUMS rats showed increased loss of hippocampal neurons （1.151±0.041,P＜0.01）,and the expression of klotho（0.910±0.032） and generation of H2S（（0.445± 0.025）nmol · mg-1 · min-1） in CUMS rats were decreased in contrast to the control（（0.621±0.019） nmol · mg-1 · min-1,P＜0.05）.The sparse neuron and inhibited neurogenesis by CUMS in hippocampus of rats were improved by NaHS administration,and the loss of hippocampal neurons in CUMS ＋ 1.68 mg/kg NaHS （1.032±0.023） or CUMS ＋5.60 mg/kg NaHS（1.045±0.038） were decreased in contrast to the CUMS rats（P＜0.01）.Compared with CUMS group,the expression of klotho in CUMS ＋ 1.68 mg/kg NaHS group （1.045±0.021）or CUMS ＋5.6 mg/kg NaHS group（1.046±0.076） was up-regulated（P＜0.05） and the generation of H2S in CUMS ＋ 1.68 mg/kg NaHS group（（0.582±0.008） nmol · mg-1 · min-1） or CUMS ＋5.6mg/kg NaHS group （（0.585 ±0.029） nmol · mg-1 · min-1） was increased （all P＜0.05）.Conclusion H2S can antagonize the neural injury-induced by chronic stress probably by upre

关 键 词：硫化氢 慢性应激 海马神经损伤 KLOTHO 神经发生 

分 类 号：R749[医药卫生—神经病学与精神病学]