硫化氢钠补充外源性硫化氢改善子代自闭症小鼠神经功能障碍  

Sodium hydrogen sulfide supplementation with exogenous H_(2)S improves neurological dysfunction in offspring autistic mice

作　　者：陈柄迪 罗耀文 程俊凯 王利 戴舒惠 王成果 张磊 CHEN Bingdi;LUO Yaowen;CHENG Junkai;WANG Li;DAI Shuhui;WANG Chengguo;ZHANG Lei(Students Third Brigade and Ninth Brigade,Basic Medical College,Air Force Medical University of PLA,Xi’an 710032,China)

机构地区：[1]空军军医大学基础医学院三大队九队,陕西西安710032 [2]空军军医大学第一附属医院神经外科,陕西西安710032 [3]空军军医大学第二附属医院普通外科,陕西西安710032

出　　处：《陕西医学杂志》2025年第1期3-8,共6页Shaanxi Medical Journal

基　　金：国家自然科学基金资助项目(81971227);陕西省自然科学基础研究计划项目(2019KW-039)。

摘　　要：目的:探讨硫氢化钠(NaHS)补充外源性硫化氢(H_(2)S)同时,通过上调3-巯基丙酮酸硫转移酶(MPST)和胱硫氨酸-β-合成酶(CBS),促进内源性H_(2)S产生,共同改善自闭症(ASDs)小鼠的神经功能障碍。方法:C57BL/6孕鼠15只,随机分为正常对照组(Con组,n=3)、2-丙基戊酸钠致ASDs模型组(VPA组,n=4)、NaHS干预组(VPA+NaHS组,n=4)和生理盐水干预对照组(VPA+NS组,n=4)。除Con组外,其余三组孕10、12 d小鼠用VPA 300 mg/kg一次性腹腔注射制备子代自闭症模型。NaHS+VPA组和NS+VPA组从孕13 d开始每天给孕鼠灌胃100μmol/kg NaHS直至子代小鼠23 d断奶。四组成活子代雄性幼鼠分别取15只进行行为学检测(高架十字迷宫实验、旷场实验和刻板行为检测)鉴定模型和治疗效果。利用H_(2)S试剂盒检测纹状体H_(2)S浓度,采用Western blot检测H_(2)S生成相关分子MPST和CBS表达情况,并利用TUNEL试剂盒检测神经细胞凋亡情况。结果:相较于Con组,VPA致自闭症谱系障碍模型可显著增加小鼠神经功能障碍(P<0.01)、下调纹状体神经细胞内MPST和CBS表达并促进凋亡(均P<0.05)。给予NaHS干预后可显著改善神经功能障碍(P<0.05),补充外源性H_(2)S的同时,还通过促进MPST和CBS表达增加内源性H_(2)S生成(均P<0.05),抑制神经细胞凋亡(P<0.05)。结论:NaHS补充外源性H_(2)S并上调与H_(2)S生成相关分子表达,抑制神经细胞凋亡,有效改善ASDs小鼠神经功能障碍。Objective:Exploring the supplementation of exogenous loydrogen sulfide(H 2S)with sodium hydrogen sulfide(NaHS)while upregulating 3-mercaptopyruvate sulfurtransferase(MPST)and cystathionineβ-synthase(CBS),promoting endogenous H_(2)S production,and jointly improving neurological dysfunction in autism spectrum disorders(ASDs)mice.Methods:Fifteen C57BL/6 pregnant mice were randomly divided into a normal control group(Con group,n=3),a valproic acid model group(VPA group,n=4),a NaHS intervention group(VPA+NaHS group,n=4),and a normal asaline control group(VPA+NS group,n=4).Except for the Con group,the offspring autism models were prepared by intraperitoneal injection of 300 mg/kg VPA in the other three groups of 12 d pregnant mice.The NaHS+VPA group and NS+VPA group were orally administered evevyday to pregnant mice starting from day 13 of pregnancy 100μmol/kg NaHS until weaning of offspring mice at 23 days.Fifteen male offspring of the four groups were selected for behavioral testing(elevated cross test,open field test,and stereotyped behavior observation)to identify the model and treatment effect.Use H_(2)S assay kit to detect the concentration of H_(2)S in the striatum,use Western blot to detect the expression of H_(2)S related molecules MPST and CBS,and use TUNEL assay kit to detect neuronal apoptosis.Results:Compared with the Con group,the VPA induced ASDs model significantly increased neurological dysfunction in mice(P<0.01),decreased the expression of MPST and CBS in neurons of striatum,and promoted cell apoptosis(all P<0.05).Conversely,NaHS significantly improve neurological dysfunction(P<0.05),increase endogenous H_(2)S generation(all P<0.05)by promoting the expression of MPST and CBS,and inhibit neuronal apoptosis(P<0.05).Conclusion:NaHS not only increase exogenous H_(2)S through enhancing the expression of molecules related to H_(2)S generation,but also inhibit neuronal apoptosis,and effectively improve neurological dysfunction in ASDs mice.

关 键 词：自闭症谱系综合征 硫氢化钠 硫化氢 凋亡 3-巯基丙酮酸硫转移酶 胱硫氨酸-β-合成酶 

分 类 号：R794[医药卫生—临床医学]