噻唑烷酸对肝组织GSH含量的影响及其作用机制的研究  

Modulation of Liver GSH Content by Thiazolidine Derivative(GlcNAcCys)

作　　者：刘吉[1] 蔡文娣[2] 杨艳[1] 刘万顺[1] 韩宝芹[1] 常菁[1] 

机构地区：[1]中国海洋大学海洋生命学院,山东青岛266003 [2]潍坊医学院,山东潍坊261042

出　　处：《中国海洋大学学报（自然科学版）》2011年第5期53-58,共6页Periodical of Ocean University of China

基　　金：山东省博士基金项目(2007BS07001);山东省自然科学基金项目(Y2008D17)资助

摘　　要：建立丁胱亚磺酰亚胺(L-Buthionine Sulfoximine,BSO)排空小鼠肝组织谷胱甘肽(Glutathione,GSH)模型,研究噻唑烷酸(N-acetyl-glucosamine-thiazolidine-4(R)-carboxylic acid,GlcNAcCys)提高肝组织GSH含量,保护肝脏免受外源性毒物、药物损伤的可能机制。正常对照组小鼠腹腔注射生理盐水,BSO组及GlcNAcCys不同剂量组小鼠注射BSO(6mmol/kg体质量,i.p.)。2 h后,正常对照组和BSO组注射生理盐水,GlcNAcCys低、中、高剂量组分别注射不同剂量的GlcNAcCys(200、4009、00 mg/kg体质量)。6 h后,用Ellman’s法测定肝匀浆总巯基(Total Sulfhydryl,T-SH)含量;荧光分光光度法测定GSH含量;用试剂盒检测肝匀浆中谷胱甘肽还原酶(Glutathione Reductase,GR)和谷胱甘肽-S转移酶(Glutathione S-transferase,GST)活性;RT-PCR法检测谷氨酰半胱氨酸连接酶催化亚基(Glutamyl-L-cysteine Ligase,GCL)基因表达。GlcNAcCys能够提高肝匀浆中T-SH和GSH含量,增强抗氧化酶GR、GST活性,RT-PCR结果显示,GlcNAcCys能够诱导GCL mRNA的表达。GlcNAcCys能够提高肝组织T-SH、GSH的含量,增强GST、GR酶活力,增强肝脏的解毒功能,保护肝脏免受毒性中间代谢物的损伤。GlcNAcCys提高肝组织T-SH、GSH含量的机制与其诱导GCLmRNA的表达有关。Liver GSH depletion mice model was established by intraperitoneal injection of L-buthionine- [S, R]-sulfoximine （BSO）and used to investigate the modulation of liver GSH content by N-Acetyl-Glu- cosamine derived thiazolidine derivative（GlcNAcCys）. Mice in control group were treated with saline, mice model group and GlcNAcCys groups were injected with BSO（i. p. 6 mmol/kg body weight）. Two hours later, mice in control and model groups were administered with saline while mice in GIcNAcCys groups were treated with different doses of GIcNAcCys （200, 400, 900 mg/kg body weight respectively）. Six hours after GlcNAcCys administration, total sulfhydryl（T-SH） content was measured by Ellman＇s method;GSH content was measured by fluorescence spectrophotometry; glutathione reductase（GR）,glu- tathione S-transferase （GST）activites in liver homogenates were tested using assay kits; liver glutamate cysteine ligase （GCL） mRNA transcription level was detected by RT PCR. GlcNAcCys administration could enhance liver T-SH and GSH content and improve liver GR, GST activies. RT-PCR data indicate that GlcNAcCys could induce GCL mRNA transcription. GlcNAcCys could improve liver T-SH and GSH content, increased GST and GR activities, enhance liver detoxification function and Protect liver from the injury of the toxic intermediate metabolite. The predominant mechanism may be related to the improvement of T-SH,GSH content and the induction GCL mRNA express.

关 键 词：噻唑烷酸 谷胱甘肽 谷氨酰半胱氨酸连接酶 谷胱甘肽还原酶 谷胱甘肽-S转移酶 

分 类 号：Q291[生物学—细胞生物学]