抗结核药物吡嗪酰胺对神经元活性的影响  

Effect of antituberculosis drug pyrazinamide on neuronal activity

作　　者：邵宏华 朱庆东[2] 龙倩 罗晓璐[4] 农剑鸿 李偲俊 吴锋耀[4] Shao Honghua;Zhu Qingdong;Long Qian;Luo Xiaolu;Nong Jianhong;Li Sijun;Wu Fengyao(Medical Department,The Fourth People's Hospital of Nanning,Guangxi Nanning 530023,China;Tuberculosis Department,The Fourth People's Hospital of Nanning,Guangxi Nanning 530023,China;Clinical Lab,The Fourth People's Hospital of Nanning,Guangxi Nanning 530023,China;Infectious Diseases Laboratory,The Fourth People's Hospital of Nanning,Guangxi Nanning 530023,China;Anesthesiology Department,The Fourth People's Hospital of Nanning,Guangxi Nanning 530023,China)

机构地区：[1]南宁市第四人民医院内科,广西南宁530023 [2]南宁市第四人民医院结核二科,广西南宁530023 [3]南宁市第四人民医院检验科,广西南宁530023 [4]南宁市第四人民医院传染病重点实验室,广西南宁530023 [5]南宁市第四人民医院麻醉科,广西南宁530023

出　　处：《新发传染病电子杂志》2023年第3期12-18,共7页Electronic Journal of Emerging Infectious Diseases

基　　金：广西重点研发项目(桂科AB19110012)。

摘　　要：目的本研究通过构建离体神经元模型,探讨抗结核药物吡嗪酰胺(PZA)对神经元活性的影响,以期为治疗结核性脑膜炎提供理论依据。方法构建离体神经元模型,用不同浓度的PZA孵育神经元6h,选取10μmol/L浓度的PZA孵育神经元12h(10-PZA-12h)和孵育神经元6h再更换正常培养基继续培养6h(10-PZA-normal-6h)。观察神经元形态结构,检测三磷酸腺苷(ATP)含量、神经元存活率、Na^(+)/K^(+)-ATP酶的α1亚基(ATP1A1)表达、神经元的静息电位(RP)和动作电位(AP)。结果10μmol/L浓度的PZA孵育神经元6h后,ATP含量、ATP1A1表达以及AP振幅均降低,RP升高。在10-PZA-12h组,神经元的结构、形态发生改变,ATP含量、细胞存活率、ATP1A1表达以及AP振幅均降低,而RP升高。在10-PZA-normal-6h组,神经元结构、形态,以及ATP含量、细胞存活率、ATP1A1、RP和AP无显著改变。结论PZA抑制神经元的细胞活性,随着药物作用时间延长,神经元出现损伤,及时祛除诱因可挽救神经元。Objective Previous study suggests that pyrazinamide(PZA),a common anti-tuberculosis drug,may lead to neuronal damage.The mechanism of neuronal damage caused by PZA remains unclear.To further investigate the potential mechanism of neuronal damage caused by PZA,We constructed an in vitro model to study the effect of PZA on neurons.Method The in-vitro neuron model were constructed,which were incubated with different concentrations of PZA for 6h.Optimal concentration of PZA was selected.Based on optimal concentration,the neurons were then incubated with PZA(10μmol/L)for 12h(10-PZA-12h),and the neurons were incubated with PZA(10μmol/L) for 6h and then replaced with normal medium for another 6h(10-PZA-normal-6h).We observed the structure and morphology of neurons and detected the ATP content,survival rate,expression of Na^(+)/K^(+)-ATPase α1 subunit(ATP1A1),electrophysiology—resting potential(RP) and action potential(AP) in neurons.Result After the neurons were incubated in PZA(10μmol/L) for 6h,the neuronal structure,morphology and survival rate were not significantly changed,but the ATP content,the expression of ATP1A1 and amplitude of AP were decreased.Inversely,the RP was increased.In 10-PZA-12h group,the morphology and structure of neurons were changed;the ATP content,neuronal survival rate,the expression of ATP1A1 and amplitude of AP were significantly decreased;the RP was increased.In 10-PZA-normal-6h group,the neuronal morphology and structure,ATP content,survival rate,the expression of ATP1A1 and amplitude of AP and RP were not significantly changed.Conclusion PZA inhibits the activity of neurons.With the extension of drug action time,the neurons appear damage,and timely removal of inducement can save neurons.

关 键 词：抗结核药物 吡嗪酰胺 神经元 三磷酸腺苷 电生理 

分 类 号：R52[医药卫生—内科学]