中华内分泌代谢杂志
中華內分泌代謝雜誌
중화내분비대사잡지
CHINESE JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2014年
12期
1068-1073
,共6页
范雨鑫%张媛媛%暴素青%范晨玲%滕卫平%单忠艳
範雨鑫%張媛媛%暴素青%範晨玲%滕衛平%單忠豔
범우흠%장원원%폭소청%범신령%등위평%단충염
妊娠%亚临床甲状腺功能减退症%胰岛素样生长因子Ⅰ%胰岛素样生长因子Ⅰ受体%磷酸化蛋白激酶B%Morris水迷宫%长时程增强
妊娠%亞臨床甲狀腺功能減退癥%胰島素樣生長因子Ⅰ%胰島素樣生長因子Ⅰ受體%燐痠化蛋白激酶B%Morris水迷宮%長時程增彊
임신%아림상갑상선공능감퇴증%이도소양생장인자Ⅰ%이도소양생장인자Ⅰ수체%린산화단백격매B%Morris수미궁%장시정증강
Pregnancy%Subclinical hypothyroidism%Insulin-like growth factor Ⅰ%Insulin-like growth factor Ⅰ receptor%Phosphorylated-protein kinase B%Morris water maze%Long-term potentiation
目的 探究妊娠期母体亚临床甲状腺功能减退(甲减)是否可以导致后代仔鼠海马胰岛素样生长因子Ⅰ (IGF-Ⅰ)、胰岛素样生长因子Ⅰ受体(IGF-Ⅰ R)和磷酸化蛋白激酶B(p-Akt)的表达降低,进而影响后代空间学习和记忆能力.方法 60只SPF级雌性Wistar大鼠随机分成3组,正常对照组(CON)20只,亚临床甲减组(SCH)20只,甲减组(CH)20只.仔鼠出生后的第3天和第7天冰上断头,分别取海马组织,以实时定量PCR方法检测IGF-Ⅰ mRNA表达,以ELISA方法检测IGF-Ⅰ、IGF-Ⅰ R蛋白表达,以Western印迹方法检测蛋白激酶B(Akt)及p-Akt蛋白表达.仔鼠出生后第40天行Morris水迷宫行为学检测及海马兴奋性突触后电位长时程增强检测.结果 与正常对照组仔鼠相比,亚临床甲减组仔鼠海马IGF-Ⅰ mRNA水平的表达在第3天和第7天时降低幅度分别为27％ (P＜0.01)和21％ (P＜0.01),IGF-Ⅰ蛋白含量的表达降低幅度分别为29％(P＜0.01)和25％ (P＜0.01),IGF-Ⅰ R蛋白的表达在第3天和第7天时降低幅度约为23％ (P＜0.01)和19％ (P＜0.05),p-Akt蛋白的表达在第3天和第7天时降低幅度约为19％(P＜0.01)和11％ (P＜0.05).与甲减组相比,仔鼠IGF-Ⅰ mRNA水平的表达和IGF-Ⅰ蛋白含量的表达在第3天和第7天时均增高(P＜0.05),而IGF-Ⅰ R和总Akt蛋白含量的表达在第3天时高于甲减组(P＜0.05),而在第7天时与甲减组表达无统计学差异(P＞0.05).第40天时,对仔鼠进行Morris水迷宫定位航向检测,各组仔鼠的逃避潜伏期均随训练天数的增加而缩短.甲减组的逃避潜伏期始终长于正常对照组.亚临床甲减组的逃避潜伏期在第1、2天与正常对照组无明显差异(P＞0.05),第3、4天逃避潜伏期长于正常对照组,有统计学差异(P=0.034;P=0.047).在第40天时对仔鼠进行兴奋性突触后电位长时程增强检测,海马经强直刺激后各组仔鼠兴奋性突触后电位的斜率均增加,亚临床甲减组仔鼠电位斜率增加百分比低于正常对照组(P＜0.05),高于甲减组(P＜0.05).结论 妊娠期母体亚临床甲减可能和仔鼠海马与长时程增强相关蛋白IGF-Ⅰ、p-Akt蛋白含量的表达降低有关,减弱了长时程增强的产生,进而损害仔鼠空间学习和记忆能力.
目的 探究妊娠期母體亞臨床甲狀腺功能減退(甲減)是否可以導緻後代仔鼠海馬胰島素樣生長因子Ⅰ (IGF-Ⅰ)、胰島素樣生長因子Ⅰ受體(IGF-Ⅰ R)和燐痠化蛋白激酶B(p-Akt)的錶達降低,進而影響後代空間學習和記憶能力.方法 60隻SPF級雌性Wistar大鼠隨機分成3組,正常對照組(CON)20隻,亞臨床甲減組(SCH)20隻,甲減組(CH)20隻.仔鼠齣生後的第3天和第7天冰上斷頭,分彆取海馬組織,以實時定量PCR方法檢測IGF-Ⅰ mRNA錶達,以ELISA方法檢測IGF-Ⅰ、IGF-Ⅰ R蛋白錶達,以Western印跡方法檢測蛋白激酶B(Akt)及p-Akt蛋白錶達.仔鼠齣生後第40天行Morris水迷宮行為學檢測及海馬興奮性突觸後電位長時程增彊檢測.結果 與正常對照組仔鼠相比,亞臨床甲減組仔鼠海馬IGF-Ⅰ mRNA水平的錶達在第3天和第7天時降低幅度分彆為27％ (P＜0.01)和21％ (P＜0.01),IGF-Ⅰ蛋白含量的錶達降低幅度分彆為29％(P＜0.01)和25％ (P＜0.01),IGF-Ⅰ R蛋白的錶達在第3天和第7天時降低幅度約為23％ (P＜0.01)和19％ (P＜0.05),p-Akt蛋白的錶達在第3天和第7天時降低幅度約為19％(P＜0.01)和11％ (P＜0.05).與甲減組相比,仔鼠IGF-Ⅰ mRNA水平的錶達和IGF-Ⅰ蛋白含量的錶達在第3天和第7天時均增高(P＜0.05),而IGF-Ⅰ R和總Akt蛋白含量的錶達在第3天時高于甲減組(P＜0.05),而在第7天時與甲減組錶達無統計學差異(P＞0.05).第40天時,對仔鼠進行Morris水迷宮定位航嚮檢測,各組仔鼠的逃避潛伏期均隨訓練天數的增加而縮短.甲減組的逃避潛伏期始終長于正常對照組.亞臨床甲減組的逃避潛伏期在第1、2天與正常對照組無明顯差異(P＞0.05),第3、4天逃避潛伏期長于正常對照組,有統計學差異(P=0.034;P=0.047).在第40天時對仔鼠進行興奮性突觸後電位長時程增彊檢測,海馬經彊直刺激後各組仔鼠興奮性突觸後電位的斜率均增加,亞臨床甲減組仔鼠電位斜率增加百分比低于正常對照組(P＜0.05),高于甲減組(P＜0.05).結論 妊娠期母體亞臨床甲減可能和仔鼠海馬與長時程增彊相關蛋白IGF-Ⅰ、p-Akt蛋白含量的錶達降低有關,減弱瞭長時程增彊的產生,進而損害仔鼠空間學習和記憶能力.
목적 탐구임신기모체아림상갑상선공능감퇴(갑감)시부가이도치후대자서해마이도소양생장인자Ⅰ (IGF-Ⅰ)、이도소양생장인자Ⅰ수체(IGF-Ⅰ R)화린산화단백격매B(p-Akt)적표체강저,진이영향후대공간학습화기억능력.방법 60지SPF급자성Wistar대서수궤분성3조,정상대조조(CON)20지,아림상갑감조(SCH)20지,갑감조(CH)20지.자서출생후적제3천화제7천빙상단두,분별취해마조직,이실시정량PCR방법검측IGF-Ⅰ mRNA표체,이ELISA방법검측IGF-Ⅰ、IGF-Ⅰ R단백표체,이Western인적방법검측단백격매B(Akt)급p-Akt단백표체.자서출생후제40천행Morris수미궁행위학검측급해마흥강성돌촉후전위장시정증강검측.결과 여정상대조조자서상비,아림상갑감조자서해마IGF-Ⅰ mRNA수평적표체재제3천화제7천시강저폭도분별위27％ (P＜0.01)화21％ (P＜0.01),IGF-Ⅰ단백함량적표체강저폭도분별위29％(P＜0.01)화25％ (P＜0.01),IGF-Ⅰ R단백적표체재제3천화제7천시강저폭도약위23％ (P＜0.01)화19％ (P＜0.05),p-Akt단백적표체재제3천화제7천시강저폭도약위19％(P＜0.01)화11％ (P＜0.05).여갑감조상비,자서IGF-Ⅰ mRNA수평적표체화IGF-Ⅰ단백함량적표체재제3천화제7천시균증고(P＜0.05),이IGF-Ⅰ R화총Akt단백함량적표체재제3천시고우갑감조(P＜0.05),이재제7천시여갑감조표체무통계학차이(P＞0.05).제40천시,대자서진행Morris수미궁정위항향검측,각조자서적도피잠복기균수훈련천수적증가이축단.갑감조적도피잠복기시종장우정상대조조.아림상갑감조적도피잠복기재제1、2천여정상대조조무명현차이(P＞0.05),제3、4천도피잠복기장우정상대조조,유통계학차이(P=0.034;P=0.047).재제40천시대자서진행흥강성돌촉후전위장시정증강검측,해마경강직자격후각조자서흥강성돌촉후전위적사솔균증가,아림상갑감조자서전위사솔증가백분비저우정상대조조(P＜0.05),고우갑감조(P＜0.05).결론 임신기모체아림상갑감가능화자서해마여장시정증강상관단백IGF-Ⅰ、p-Akt단백함량적표체강저유관,감약료장시정증강적산생,진이손해자서공간학습화기억능력.
Objective To investigate the effect of subclinical hypothyroidism during pregnancy on hippocampus insulin-like growth factor Ⅰ (IGF-Ⅰ) signaling pathway in rat offspring.Methods A total of 60 female Wistar rats were evenly divided into control(CON),subclinical hypothyroidism(SCH),and clinical hypothyroidism (CH) groups.The hippocampus of progenies were collected on the postnatal day 3,postnatal day 7 to measure protein kinase B (Akt) and phosphorylated-Akt (p-Akt) by Western blot,IGF-Ⅰ and insulin-like growth factor Ⅰ receptor (IGF-Ⅰ R) by Elisa.Morris water maze and field excitatory postsynaptic potential long-term potentiation were measured at the postnatal 40 day.Results Western blot and Elisa revealed that levels of IGF-Ⅰ,IGF-Ⅰ R,and p-Akt of pups from SCH group were lower than that of CON group and were higher than CH group on day 3 (P ＜ 0.05).On day 7,the levels of IGF-Ⅰ,IGF Ⅰ R,and p-Akt of pups from SCH group were lower than CON group (P＜ 0.05),but no difference was observed in p-Akt and IGF-Ⅰ R level between SCH group and CH group (P ＞ 0.05).Latencies of all groups had shortened in Morris water maze test with increasing of training trials.The slope of field excitatory postsynaptic potenial was increased in all groups after Theta burst stimulation.The amplification percentage of slope of field excitatory postsynaptic potenial in SCH group's was lower than control group's but was higher than CH group's(all P values＜0.05).Conclusions Maternal subclinical hypothyroidism impairs long-term potentiation induction in hippocampus of rat might be associated with the levels of IGF-Ⅰ,IGF-Ⅰ R,and p-Akt.
