刀豆蛋白A致小鼠肝损伤的LTC_4合成酶系基因表达及环孢素A调控作用  

Gene expressions of LTC_4 synthase homologs in Con A-induced mouse hepatitis and regulative effect of cyclosporine A

作　　者：齐罗扬[1] 马葵芬[1] 来芳芳[1] 杜悦[1] 朱丹雁[1] 楼宜嘉[1] 

机构地区：[1]浙江大学药学院药理毒理与生化药学研究所,浙江杭州310058

出　　处：《浙江大学学报（医学版）》2007年第3期241-246,共6页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金项目(No.30672564;No.30472112;No.30070904);浙江省自然科学基金项目(No.Y206473).

摘　　要：目的:探索白三烯C4(LTC4)合成酶系在小鼠刀豆蛋白A(Con A)肝损伤时的基因表达谱,及环孢素A(Cs A)对其表达水平的调控。方法:雄性Balb/c小鼠尾静脉注射Con A致肝损伤,另设尾静脉注射Cs A预给药。检测血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)评价肝功能,光镜检查肝组织学损伤,RT-PCR检测肝LTC4合酶(LTC4S)、微粒体谷胱甘肽S-转移酶2(mGST2)和mGST3基因的表达。结果:血清转氨酶和病理组织学结果表明:Con A注射2h后肝脏即有明显损伤,8h达到高峰;mGST2基因表达在2h明显上调(170%),8h达高峰(190%),而LTC4S和mGST3基因表达无明显改变。Cs A预给药可阻断Con A引起的肝脏损伤,并部分抑制mGST2基因表达上调,但对LTC4S和mGST3基因表达无影响。结论:Con A致小鼠肝损伤时,mGST2基因表达显著上调,而LTC4S和mGST3基因表达差异不明显。Cs A预处理能有效阻断ConA引起的肝损伤,但不能完全抑制mGST2基因表达上调。Objective. To explore the gene expressions of LTC4 concanavalin A （Con A）-induced mouse hepatitis and regulation role of treatment. Methods ： Male Balb/c mouse liver injury model was developed （20 mg/kg） and protected by Cs A pretreatment （150 mg/kg） before Blood samples were collected at indicated times after Con A treatment synthase homologs in cyclosporine A （Cs A） by iv injection of Con A Con A administration. with or without Cs A pretreatment. Liver damage was assessed by serum transaminase ALT and AST measurement and histological evaluation. Meantime, three LTC4 synthase homolog gene expressions were determined by RT-PCR. Results： Serum ALT and AST upregulation were accompanied with histological damage at 2 h after Con A administration,and further aggravated at 8 h. mGST2 gene expression increased 1. 7 fold at 2 h and 1. 9 fold at 8 h,while the expression of LTC4S and mGST3 changed little. Pretreatment with Cs A prevented mouse liver from injury by Con A and partly inhibited the mGST2 gene expression upregulation. Conclusions. Administration of Con A in mouse lead to a significant increase of mGST2 gene expression without any significant effect on LTC4 S and mGST3 mRNA levels. Cs A pretreatment results in protection of liver damage, whereas fails to fully inhibit the increase of mGST2 gene expression.

关 键 词：白三烯C4 伴刀豆球蛋白A/副作用 环孢菌素/药理学 肝/损伤 肝/病理学 谷胱甘肽转移酶 基因表达 

分 类 号：R965[医药卫生—药理学]