食蟹猴CCl4给药前后的血清差异蛋白鉴定  

Identification of serum differential proteins in Macaca fascicularis before and after CCl4 administrationIdentification of serum differential proteins in Macaca fascicularis before and after CCl_4 administration

作　　者：苗玉发[1] 李伟[1] MIAO Yufa;LI Wei(Beijing Key Laboratory for Safety Evaluation of Drugs,NCSED,NIFDC,Beijing 100176,China)

机构地区：[1]中国食品药品检定研究院国家药物安全评价监测中心药物非临床安全评价研究北京市重点实验室,北京100176

出　　处：《生物技术》2025年第1期44-49,共6页Biotechnology

基　　金：国家“重大新药创制”科技重大专项(2018ZX09201017-001-003)。

摘　　要：[目的]比较雌性和雄性食蟹猴CCl4给药前后及性别间的血清差异蛋白。[方法]12只食蟹猴CCl4给药前以及给药后48 h,取血制备血清。部分血清用于肝酶测定,部分血清用于蛋白质提取。采用iTRAQ和LC-MS/MS技术,对蛋白质进行鉴定。[结果]CCl4给药前,异性间的显著性差异指标有碱性磷酸酶(alkaline phosphatase,ALP);CCl4给药后,异性间的显著性差异指标有ALP、乳酸脱氢酶(lactate dehydrogenase,LDH)和磷酸肌酸激酶(creatine kinase,CK)。对于雌性,给药前后谷氨酸转氨酶(alanine aminotransferase,ALT)、天冬氨酸转氨酶(aspartate aminotransferase,AST)、CK和LDH的差异显著(P<0.01)。对于雄性,给药前后ALT的差异显著(P<0.01)。CCl4给药前、后雌雄异性间的差异蛋白分别为79个和258个。雌性在CCl4给药前后的差异蛋白为374个,雄性在CCl4给药前后的差异蛋白为376个。[结论]鉴定出的CCl4给药前、后雌雄异性间的79个和258个差异蛋白是对外源毒物或药物的免疫反应和毒性反应产生性别间差异的部分原因。CCl4给药前及给药后的750个差异蛋白参与CCl4的毒性机制。[Objective]To compare the differential proteins in the peripheral blood of female and male Macaca fascicularis before and after CCl_(4)administration.[Method]Twelve Macaca fascicularis were given CCl_4 by gavage.Blood samples were obtained to prepare serum before and at 48 hours after administration.Part of the serum was used for the determination of liver enzyme and part of serum was used to extract proteins.The proteins were identified and compared using the techniques of iTRAQ and LC-MS/MS.[Result]Before CCl_4 administration,the significant difference indexe between the opposite sex was ALP,while after CCl_4 administration,the significant difference indexes between the opposite sex were ALP,LDH and CK.For female animals,the differences of ALT,AST,CK and LDH before and after administration were statistically significant(P<0.01).For male animals,the difference of ALT before and after administration was statistically significant.There were 79 and 258 differential proteins between sexes before and after CCl_4 administration,respectively.There were 374 differential proteins in female and 376 differential proteins in male before and after CCl_4 administration.[Conclusion]The 79 and 258 differential proteins between male and female identified before and after administration of CCl_4 were partly responsible for sex differences in immune and toxic responses to exogenous poisons or drugs.The 750 differential proteins before and after CCl_4 administration participated in the toxicity mechanism of CCl_4.

关 键 词：食蟹猴 蛋白质组学 iTRAQ技术 液相色谱质谱串联 性别差异 基因本体 京都基因和基因组百科全书 蛋白质互相作用网络 

分 类 号：R994[医药卫生—毒理学]