目的 探讨功夫菊酯(LCT)是否干扰雌激素作用而影响海马突触发育.方法 出生后28 d(PND28)的健康雌性ICR小鼠随机分为假手术和卵巢切除两大组,假手术组分为假手术对照组、假手术LCT组(3.0 μg/g)、假手术来曲唑组(1.0 μg/g)及假手术LCT+来曲唑组,卵巢切除组分为卵巢切除对照组、卵巢切除雌激素组(10.0 μg/g)、卵巢切除LCT组、卵巢切除来曲唑组、卵巢切除雌激素+LCT组、卵巢切除雌激素+来曲唑组、卵巢切除LCT+来曲唑组、卵巢切除雌激素+LCT+来曲唑组,共12小组,每组10只,经腹腔注射给药,连续2d,末次给药24 h后对各组半数动物进行行为学测试,余下动物麻醉取脑做冰冻切片,用免疫荧光组织化学技术检测突触后致密蛋白95(PSD 95).结果 行为学测试发现,与假手术对照组比较,卵巢切除对照组小鼠在旷场第1格潜伏期和水迷宫登台潜伏期明显延长,差异有统计学意义(P＜0.05);与卵巢切除对照组比较,卵巢切除雌激素组小鼠在旷场中跨越的总格数增加,水迷宫登台潜伏期缩短,差异有统计学意义(P＜0.05);与卵巢切除雌激素组比较,卵巢切除雌激素+LCT组总格数和站立次数明显减少,登台潜伏期延长,差异有统计学意义(P＜0.05);与假手术对照组比较,假手术LCT小鼠登台潜伏期延长,差异有统计学意义(P＜0.05);与卵巢切除对照组比,卵巢切除LCT组小鼠第1格潜伏期及登台潜伏期缩短,差异有统计学意义(P＜0.05);与假手术来曲唑组比较,假手术LCT+来曲唑组小鼠在旷场第1格潜伏期延长,跨越总格数和站立次数减少,差异有统计学意义(P＜0.05).免疫荧光组织化学检测发现,与假手术对照组比较,卵巢切除对照组海马CA1、CA3和DG区PSD95表达明显降低,差异有统计学意义(P＜0.05);与卵巢切除对照组比较,卵巢切除雌激素(或LCT)组PSD95表达有所上调,差异有统计学意义(P＜0.05);与假手术对照组比较,假手术LCT组PSD95表达下调,差异有统计学意义(P＜0.05);与卵巢切除雌激素组比较,卵巢切除雌激素+LCT组PSD95表达下调,差异有统计学意义(P＜0.05);与卵巢切除雌激素+来曲唑组比较,卵巢切除雌激素+LCT+来曲唑组CA3区PSD95表达下调,差异有统计学意义(P＜0.05);与卵巢切除来曲唑组比较,卵巢切除LCT+来曲唑组DG区PSD95表达上调,差异有统计学意义(P＜0.05).结论 在体内雌激素极低或被清除的条件下,LCT可模拟雌激素对海马突触发育的促进作用;循环雌激素存在时,LCT可干扰雌激素的效应,抑制海马突触发育.这很可能是LCT神经发育毒性的重要作用机制.
目的 探討功伕菊酯(LCT)是否榦擾雌激素作用而影響海馬突觸髮育.方法 齣生後28 d(PND28)的健康雌性ICR小鼠隨機分為假手術和卵巢切除兩大組,假手術組分為假手術對照組、假手術LCT組(3.0 μg/g)、假手術來麯唑組(1.0 μg/g)及假手術LCT+來麯唑組,卵巢切除組分為卵巢切除對照組、卵巢切除雌激素組(10.0 μg/g)、卵巢切除LCT組、卵巢切除來麯唑組、卵巢切除雌激素+LCT組、卵巢切除雌激素+來麯唑組、卵巢切除LCT+來麯唑組、卵巢切除雌激素+LCT+來麯唑組,共12小組,每組10隻,經腹腔註射給藥,連續2d,末次給藥24 h後對各組半數動物進行行為學測試,餘下動物痳醉取腦做冰凍切片,用免疫熒光組織化學技術檢測突觸後緻密蛋白95(PSD 95).結果 行為學測試髮現,與假手術對照組比較,卵巢切除對照組小鼠在曠場第1格潛伏期和水迷宮登檯潛伏期明顯延長,差異有統計學意義(P＜0.05);與卵巢切除對照組比較,卵巢切除雌激素組小鼠在曠場中跨越的總格數增加,水迷宮登檯潛伏期縮短,差異有統計學意義(P＜0.05);與卵巢切除雌激素組比較,卵巢切除雌激素+LCT組總格數和站立次數明顯減少,登檯潛伏期延長,差異有統計學意義(P＜0.05);與假手術對照組比較,假手術LCT小鼠登檯潛伏期延長,差異有統計學意義(P＜0.05);與卵巢切除對照組比,卵巢切除LCT組小鼠第1格潛伏期及登檯潛伏期縮短,差異有統計學意義(P＜0.05);與假手術來麯唑組比較,假手術LCT+來麯唑組小鼠在曠場第1格潛伏期延長,跨越總格數和站立次數減少,差異有統計學意義(P＜0.05).免疫熒光組織化學檢測髮現,與假手術對照組比較,卵巢切除對照組海馬CA1、CA3和DG區PSD95錶達明顯降低,差異有統計學意義(P＜0.05);與卵巢切除對照組比較,卵巢切除雌激素(或LCT)組PSD95錶達有所上調,差異有統計學意義(P＜0.05);與假手術對照組比較,假手術LCT組PSD95錶達下調,差異有統計學意義(P＜0.05);與卵巢切除雌激素組比較,卵巢切除雌激素+LCT組PSD95錶達下調,差異有統計學意義(P＜0.05);與卵巢切除雌激素+來麯唑組比較,卵巢切除雌激素+LCT+來麯唑組CA3區PSD95錶達下調,差異有統計學意義(P＜0.05);與卵巢切除來麯唑組比較,卵巢切除LCT+來麯唑組DG區PSD95錶達上調,差異有統計學意義(P＜0.05).結論 在體內雌激素極低或被清除的條件下,LCT可模擬雌激素對海馬突觸髮育的促進作用;循環雌激素存在時,LCT可榦擾雌激素的效應,抑製海馬突觸髮育.這很可能是LCT神經髮育毒性的重要作用機製.
목적 탐토공부국지(LCT)시부간우자격소작용이영향해마돌촉발육.방법 출생후28 d(PND28)적건강자성ICR소서수궤분위가수술화란소절제량대조,가수술조분위가수술대조조、가수술LCT조(3.0 μg/g)、가수술래곡서조(1.0 μg/g)급가수술LCT+래곡서조,란소절제조분위란소절제대조조、란소절제자격소조(10.0 μg/g)、란소절제LCT조、란소절제래곡서조、란소절제자격소+LCT조、란소절제자격소+래곡서조、란소절제LCT+래곡서조、란소절제자격소+LCT+래곡서조,공12소조,매조10지,경복강주사급약,련속2d,말차급약24 h후대각조반수동물진행행위학측시,여하동물마취취뇌주빙동절편,용면역형광조직화학기술검측돌촉후치밀단백95(PSD 95).결과 행위학측시발현,여가수술대조조비교,란소절제대조조소서재광장제1격잠복기화수미궁등태잠복기명현연장,차이유통계학의의(P＜0.05);여란소절제대조조비교,란소절제자격소조소서재광장중과월적총격수증가,수미궁등태잠복기축단,차이유통계학의의(P＜0.05);여란소절제자격소조비교,란소절제자격소+LCT조총격수화참립차수명현감소,등태잠복기연장,차이유통계학의의(P＜0.05);여가수술대조조비교,가수술LCT소서등태잠복기연장,차이유통계학의의(P＜0.05);여란소절제대조조비,란소절제LCT조소서제1격잠복기급등태잠복기축단,차이유통계학의의(P＜0.05);여가수술래곡서조비교,가수술LCT+래곡서조소서재광장제1격잠복기연장,과월총격수화참립차수감소,차이유통계학의의(P＜0.05).면역형광조직화학검측발현,여가수술대조조비교,란소절제대조조해마CA1、CA3화DG구PSD95표체명현강저,차이유통계학의의(P＜0.05);여란소절제대조조비교,란소절제자격소(혹LCT)조PSD95표체유소상조,차이유통계학의의(P＜0.05);여가수술대조조비교,가수술LCT조PSD95표체하조,차이유통계학의의(P＜0.05);여란소절제자격소조비교,란소절제자격소+LCT조PSD95표체하조,차이유통계학의의(P＜0.05);여란소절제자격소+래곡서조비교,란소절제자격소+LCT+래곡서조CA3구PSD95표체하조,차이유통계학의의(P＜0.05);여란소절제래곡서조비교,란소절제LCT+래곡서조DG구PSD95표체상조,차이유통계학의의(P＜0.05).결론 재체내자격소겁저혹피청제적조건하,LCT가모의자격소대해마돌촉발육적촉진작용;순배자격소존재시,LCT가간우자격소적효응,억제해마돌촉발육.저흔가능시LCT신경발육독성적중요작용궤제.
Objective To explore the effects of λ-cyhalothrin on hippocampus by intertering with estrogen.Methods The healthy female ICR mice of postnatal 28 days were random divided into 12 groups,4 of those were sham-operation include control,λ-cyhalothrin(LCT,3.0 μg/g),Letrozole (Let,1.0 μg/g),and LCT (3.0 μg/g)+Let(1.0 μg/g); and the last 8 were ovariectomized include OVX,Estradiol (E2,10.0 μg/g),LCT,Let,E2+LCT,E2+Let,LCT+Let,E2 +LCT+Let.10 mice in every group received drugs by intraperitoneal injection for 2 days.Then half of every group initiate the ethological test(open field test and Morris water maze) 24 h later.The last half animals were sacrificed to made frozen section for immunofluorescent assay of postsynaptic density protein 95 (PSD95).Results In ethological test,campared with Sham,OVX can lengthen incubation period in the first grid and to get on the platform (P＜0.05); campared with OVX,OVX+E2 can increase the total numbers of through grid and shorten the incubation period to get on the platform (P＜0.05); campared with OVX+E2,OVX +E2 +LCT can reduce the number of grid and standing,lengthen incubation period to the platform (P＜0.05); campared with Sham,Sham +LCT can lengthen incubation period to the platform of Sham mice (P＜0.05),but campared with OVX,OVX+LCT can shoten incubation period in the first grid and to get on the platform in OVX mice (P＜0.05); campared with Sham+Let,Sham+LCT+Let can lengthen incubation period in the first grid,reduce the the number of grid and standing (P ＜0.05).In the Immunohistochemical fluorescence experiment we find that,campared with Sham,OVX can reduce the expression of PSD95 in CA1,CA3 and DG(P＜0.05); however campared with OVX,E2 or LCT can both inhibit the effect of OVX (P＜0.05); campared with Sham,Sham+LCT can reduce the expression of PSD95,the same result when OVX+E2+LCT campared with OVX+E2 (P＜0.05); campared with OVX+E2+Let,OVX+E2+LCT+ Let can reduce the expression of PSD95 in CA3 (P＜0.05); campared with OVX+Let,OVX+LCT+Let can increase the expression of PSD95 in DG(P＜0.05).Conclusions When few estrogen exist in the body,LCT can show estrogen-like action to promote hippocampal synaptic development; but when circulating estrogen exist,LCT can inhibit synaptic development by interfering estrogen.
