替诺福韦对子代大鼠认知功能的影响及其机制  

Effect and Mechanism of Action of Tenofovir on Cognitive Function in Rats

作　　者：陈巧真[1] 孙敏[1] CHEN Qiaozhen;SUN Min(Department of Hepatology,Jining Infectious Diseases Hospital,Jining 272031,China)

机构地区：[1]山东省济宁市传染病医院肝病科,山东济宁272031

出　　处：《中国医科大学学报》2018年第10期909-913,共5页Journal of China Medical University

基　　金：山东省高等学校科技计划(J10LF01);济宁市科技发展计划(2016-56-70)

摘　　要：目的分析替诺福韦对子代鼠认知功能的影响。方法将24只Wistar妊娠大鼠分为3组,每组8只,在大鼠妊娠12~21 d时给予处置。对照组给予生理盐水肌注10 d,低浓度替诺福韦组按照2.25 mg·kg-1·d-1注射替诺福韦,高浓度替诺福韦组按照4.5mg·kg-1·d-1注射替诺福韦。妊娠第22天,在对各组孕鼠进行血气分析后剖腹取出子代鼠,记录子代鼠的体质量。子代鼠出生4周后,每组取4只子代鼠进行定位航行测试以及空间探索测试。每组取4只子代鼠,采用Western blotting及实时PCR检测大脑海马组织中GSK-3β、β-catenin及nestin的变化情况。结果不同浓度的替诺福韦未对孕鼠的血气分析结果及子代鼠的体质量造成影响。低浓度替诺福韦组与对照组比较,子代鼠逃避潜伏期以及目标象限活动次数和时间的差异无统计学意义(P> 0.05)。而高浓度替诺福韦组子代鼠逃避潜伏期与对照组、低浓度替诺福韦组比较明显延长,目标象限活动次数和时间缩短,差异有统计学意义(P <0.05)。与对照组和低浓度替诺福韦组相比,高浓度替诺福韦组子代鼠的GSK-3β表达上调(P <0.05),β-catenin及nestin表达下调(P <0.05)。结论低浓度替诺福韦不会对子代鼠的学习记忆能力造成影响,高浓度替诺福韦可能抑制子代鼠的学习记忆功能。Objective To explore the effect of tenofovir on cognitive function in rat offspring.Methods Pregnant Wistar rats were divided into 3 groups(n=8 each group).At 12-21 days of gestation,the control group was given normal saline for 10 days,and the low-and high-concentration tenofovir groups were injected with 2.25 and 4.5 mg·kg-1·d-1 tenofovir,respectively.On the 22nd day of gestation,after blood gas analysis was performed in pregnant rats,the offspring were removed to record body weight.After 4 weeks,navigation and space exploration tests were performed in 4 offspring rats of each group,and the expression of GSK-3β,β-catenin,and nestin was determined with Western blotting and real-time PCR in 4 other rats.Results No effect of different concentrations of tenofovir was found on blood gas analysis in pregnant rats and on the body weight of the offspring.No significant difference in escape latency and target quadrant time was found between the control and low-concentration tenofovir groups.The escape latency was longer,target quadrant time was shorter,expression of GSK-3βwas higher,and expression ofβ-catenin and nestin was lower in the high-concentration tenofovir group(P<0.05)than in the control and low-concentration tenofovir groups.Conclusion A low concentration of tenofovir does not affect cognitive function in offspring,and a high concentration of tenofovir may inhibit cognitive function in offspring.

关 键 词：替诺福韦 子代 认知功能 

分 类 号：R587[医药卫生—内分泌]