国际医药卫生导报
國際醫藥衛生導報
국제의약위생도보
INTERNATIONAL MEDICINE & HEALTH GUIDANCE NEWS
2011年
23期
2863-2867
,共5页
血红素加氧酶-1%硫化氢%顺铂%氧化应激%听细胞
血紅素加氧酶-1%硫化氫%順鉑%氧化應激%聽細胞
혈홍소가양매-1%류화경%순박%양화응격%은세포
Heme oxygenase 1%Hydrogen sulfide%,Cisplatin%Oxidative stress%Auditory cells
目的 探讨血红素加氧酶-1(HO-1)在硫化氢(H2S)对抗顺铂(Cisplatin)诱导的听细胞损伤中的作用.方法 应用顺铂处理听细胞,建立化疗药物耳毒性的体外模型.硫化氢的供体硫氢化钠( NaHS)及HO-1抑制剂锌原卟啉Ⅸ(ZnPPⅨ)先于顺铂加入培养基中,作为预处理.检测细胞存活率、胞内丙二醛( MDA)的含量、HO-1的表达.结果 顺铂在10～80μmol/L浓度范围内处理听细胞24h可浓度依赖性地降低细胞存活率.40μmol/L顺铂处理24 h可增加听细胞内MDA的含量.NaHS处理可上调HO-1的表达,抑制顺铂引起的胞内MDA含量增加及细胞存活率降低.HO-1的抑制剂棗ZnPPⅨ可明显减弱H2S对顺铂诱导的胞内MDA含量的增加及细胞存活率降低的抑制作用.结论 HO-1可通过抗氧化的机制介导H2S对顺铂诱导的听细胞毒性的改善作用.
目的 探討血紅素加氧酶-1(HO-1)在硫化氫(H2S)對抗順鉑(Cisplatin)誘導的聽細胞損傷中的作用.方法 應用順鉑處理聽細胞,建立化療藥物耳毒性的體外模型.硫化氫的供體硫氫化鈉( NaHS)及HO-1抑製劑鋅原卟啉Ⅸ(ZnPPⅨ)先于順鉑加入培養基中,作為預處理.檢測細胞存活率、胞內丙二醛( MDA)的含量、HO-1的錶達.結果 順鉑在10～80μmol/L濃度範圍內處理聽細胞24h可濃度依賴性地降低細胞存活率.40μmol/L順鉑處理24 h可增加聽細胞內MDA的含量.NaHS處理可上調HO-1的錶達,抑製順鉑引起的胞內MDA含量增加及細胞存活率降低.HO-1的抑製劑棗ZnPPⅨ可明顯減弱H2S對順鉑誘導的胞內MDA含量的增加及細胞存活率降低的抑製作用.結論 HO-1可通過抗氧化的機製介導H2S對順鉑誘導的聽細胞毒性的改善作用.
목적 탐토혈홍소가양매-1(HO-1)재류화경(H2S)대항순박(Cisplatin)유도적은세포손상중적작용.방법 응용순박처리은세포,건립화료약물이독성적체외모형.류화경적공체류경화납( NaHS)급HO-1억제제자원계람Ⅸ(ZnPPⅨ)선우순박가입배양기중,작위예처리.검측세포존활솔、포내병이철( MDA)적함량、HO-1적표체.결과 순박재10～80μmol/L농도범위내처리은세포24h가농도의뢰성지강저세포존활솔.40μmol/L순박처리24 h가증가은세포내MDA적함량.NaHS처리가상조HO-1적표체,억제순박인기적포내MDA함량증가급세포존활솔강저.HO-1적억제제조ZnPPⅨ가명현감약H2S대순박유도적포내MDA함량적증가급세포존활솔강저적억제작용.결론 HO-1가통과항양화적궤제개도H2S대순박유도적은세포독성적개선작용.
Objective To explore the roles of beme oxygenase 1 ( HO-1 ) in the protection of hydrogen sulfide ( H2S ) against cisplatin-induced injuries in auditory cells.Methods Auditory cells were treated with cisplatin to establish a chemotherapeutics-inducel ototoxicity model.Sodium hydrosulfide ( NaHS,a H2S donor )was added into medium for 1 h before cisplatin treatment.To inhibit the role of HO-1,zine protoporphyrin IX ( ZnPPIX )was used at the time of treatment with NaHS and cisplatin.Cell viabihty was tested by using the cell counting kit ( CCK-8 ).Level of intercellular MDA was detected by a commercial kit.The expressions of HO-1 and cleaved caspase-3 were detected by Western blot.Apoptotic rate was determined by propidium iodide staining and flow cytometry.Results Cisplatin at 10～80 μmol/L for 24h significantly induced cytotoxicity,reducing cell viability.Treatment with cisplatin of 40 μmol/L for 24 hincreased the level of intercellular MDA,expression of cleaved caspase-3,and rate of cellular apoptosis.Pretreatment with NaHS at different concentrations dramatically attenuated the decrease in cell viability induced by cisplatin,and also inhibited an increase in intercellular MDA level,expression of cleaved caspse-3,and rate of apoptosis induced by cisplatin.By inhibiting the role of HO-1,ZnPPIX blocked the inhibitory effects of H2S on an increase in intercellular M DA induced by cisplatin,overexpression of cleaved caspase-3,and apoptosis.Conclusions HO-1 may mediate auditory cells protection of H2S via inhibiting oxidative stress and cisplatin- induced apoptosis.
