鸡矢藤环烯醚萜苷抑制NO-CGMP/PKG信号保护新生大鼠神经元  

Iridoid glycosides from Paederia Scandens protect neurons of fetal rats by inhibiting NO-cGMP/PKG signal

作　　者：王坤[1,2] 胡才彪 章成[1,2] 秦志强 周兰兰 WANG Kun;HU Cai-biao;ZHANG Cheng;QIN Zhi-qiang;ZHOU Lan-lan(Dept of Pharmacology,Anhui Medical University,Hefei 230032,China;Medical College,Shenzhen Polytechnic,Shenzhen,Guangdong 518055,China)

机构地区：[1]安徽医科大学药理学教研室,安徽合肥230032 [2]深圳职业技术学院医护学院,广东深圳518055

出　　处：《中国药理学通报》2020年第11期1569-1573,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81870957)。

摘　　要：目的本研究旨在探讨鸡矢藤环烯醚萜苷(iridoid glycosides from Paederia scandens,IGPS)通过抑制NO-cGMP/PKG信号通路,保护新生大鼠神经节(dorsal root ganglia,DRG)神经元的作用。方法SD大鼠连续灌胃给药后,采集血清制备IGPS含药血清;采用硝普钠(sodium nitroprusside,SNP)200μmol·L^-1制备DRG神经元损伤模型;MTT法测定IGPS含药血清对SNP损伤后DRG神经元存活率的影响;紫外分光光度法测定DRG神经元NO含量和iNOS活性;放射免疫分析法测定DRG神经元cGMP含量;RT-PCR法检测DRG神经元PKGΙ(α,β)mRNA的表达;激光共聚焦显微镜检测DRG神经元胞内钙离子浓度的变化。结果IGPS含药血清可明显升高SNP损伤后DRG神经元的存活率,明显降低DRG神经元NO、cGMP含量及iNOS活性,抑制iNOSmRNA、PKGΙ(α,β)mRNA的表达。IGPS含药血清可有效抑制损伤DRG胞内钙离子浓度的升高。结论IGPS含药血清对SNP导致的背根神经节神经元损伤有良好保护作用,其机制可能与抑制cGMP/PKG信号及降低胞内钙离子浓度有关。Aim To investigate the protective effect of iridoid glycosides from Paederia Scandens(IGPS)on the injury of dorsal root ganglion(DRG)neurons by inhibiting NO-cGMP/PKG signal in fetal rats.Methods The serum of SD rats was collected after continuous intragastric administration to prepare IGPS-containing serum.DRG neuron injury model was prepared with 200μmol·L^-1 of sodium nitroprusside(SNP).MTT assay was used to determine the effect of IGPS-containing serum on the survival rate in SNP injured DRG neurons.Nitric oxide(NO)content and iNOS activity of DRG neurons were determined by UV spectrophotometry.The cGMP content of DRG neurons was determined by radioimmunoassay.The expression of PKGΙ(α,β)mRNA and intracellular calcium concentration of DRG neurons was detected separately by RT-PCR and laser confocal microscope.Results IGPS-containing serum could significantly increase the survival rate of DRG neurons caused by SNP injury,and markedly reduce the contents of NO,cGMP level and iNOS activity in DRG neurons.In addition,IGPS could also down-regulate the expression of iNOS mRNA and PKGΙ(α,β)mRNA and inhibit the increase of intracellular calcium ion concentration in injured DRG.Conclusions IGPS-containing serum exerts protective effect on SNP-induced dorsal root ganglion neuron injury,and its mechanism may be related to the inhibition of cGMP/PKG signal and reduction of intracellular calcium concentration.

关 键 词：鸡矢藤环烯醚萜苷 背根神经节 一氧化氮 cGMP/PKG 胞内钙 

分 类 号：R-332[医药卫生] R284.1