中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2015年
2期
277-283
,共7页
郭自景%徐丹%罗瀚文%邓梓辛%钟卫华%汪晖
郭自景%徐丹%囉瀚文%鄧梓辛%鐘衛華%汪暉
곽자경%서단%라한문%산재신%종위화%왕휘
尼古丁%宫内发育迟缓%跨代遗传%糖代谢%脂代谢
尼古丁%宮內髮育遲緩%跨代遺傳%糖代謝%脂代謝
니고정%궁내발육지완%과대유전%당대사%지대사
nicotine%intrauterine growth retardation%transgenerational inheritance%glucose metab-olism%lipid metabolism
目的:探讨孕期尼古丁暴露所致宫内发育迟缓(lUGR)子代大鼠神经内分泌代谢编程改变的跨代遗传效应。方法 Wistar 大鼠孕11 d 起每天 sc 给予尼古丁2 mg??kg-1至分娩。子1代(F1)正常组和尼古丁组 lUGR 交叉配对而得子2代(F2):CC 组(亲氏为正常 F1)、CN 组(父为正常 F1,母为lUGR F1)、NC 组(父为 lUGR F1,母为正常 F1)和 NN 组(亲氏为lUGR F1)。成年 F2给予2周冰水游泳刺激,收集刺激前、后血样,采用放免试剂盒检测血清促肾上腺皮质激素( ACTH)水平, ELlSA 试剂盒检测皮质酮(CORT)水平,生化试剂盒检测葡萄糖、甘油三酯(TG)和总胆固醇(TCH)水平。结果慢性刺激前,NN 组雄性子代血清 CORT 较 CC 组显著降低,为 CC 组的73.9%(P<0.05),CN 和 NC 组雄性子代血清 TG 分别升高到 CC 组的1.43和1.52倍(P<0.05),同时 CN, NC 和 NN 组雌性子代血清 TG 分别升高到 CC 组的1.71,1.80和1.81倍(P<0.05);慢性刺激后,CC 组雄性子代血清 CORT 增加率为-1.67%,而 NN 组雄性子代血清 CORT 增加率为36.0%,NC 组雄性及 CN 组雌性子代血糖显著升高,分别升高至各自 CC 对照组的1.61和1.62倍(P<0.01),同时各尼古丁组雌、雄中子代血清 TG 增加率均较 CC 组显著降低(P<0.05),具体表现为 CN, NC 和 NN 组雄性子代血清 TG 增加率分别降低至 CC 组的46.4%,16.7%和7.7%,而相应雌性子代血清 TG 增加率分别降低至 CC 组的20.6%,4.0%和8.4%。与 CC 组相比,慢性刺激前,NN 组雌、雄性子代血清 TCH 分别下降40.5%和21.9%(P<0.01);慢性刺激后,雌性子代 TCH 增长率升高49.7%(P<0.05)。结论孕期尼古丁暴露致大鼠神经内分泌代谢编程改变具有跨代遗传效应,且具有一定的性别和亲源性差异。
目的:探討孕期尼古丁暴露所緻宮內髮育遲緩(lUGR)子代大鼠神經內分泌代謝編程改變的跨代遺傳效應。方法 Wistar 大鼠孕11 d 起每天 sc 給予尼古丁2 mg??kg-1至分娩。子1代(F1)正常組和尼古丁組 lUGR 交扠配對而得子2代(F2):CC 組(親氏為正常 F1)、CN 組(父為正常 F1,母為lUGR F1)、NC 組(父為 lUGR F1,母為正常 F1)和 NN 組(親氏為lUGR F1)。成年 F2給予2週冰水遊泳刺激,收集刺激前、後血樣,採用放免試劑盒檢測血清促腎上腺皮質激素( ACTH)水平, ELlSA 試劑盒檢測皮質酮(CORT)水平,生化試劑盒檢測葡萄糖、甘油三酯(TG)和總膽固醇(TCH)水平。結果慢性刺激前,NN 組雄性子代血清 CORT 較 CC 組顯著降低,為 CC 組的73.9%(P<0.05),CN 和 NC 組雄性子代血清 TG 分彆升高到 CC 組的1.43和1.52倍(P<0.05),同時 CN, NC 和 NN 組雌性子代血清 TG 分彆升高到 CC 組的1.71,1.80和1.81倍(P<0.05);慢性刺激後,CC 組雄性子代血清 CORT 增加率為-1.67%,而 NN 組雄性子代血清 CORT 增加率為36.0%,NC 組雄性及 CN 組雌性子代血糖顯著升高,分彆升高至各自 CC 對照組的1.61和1.62倍(P<0.01),同時各尼古丁組雌、雄中子代血清 TG 增加率均較 CC 組顯著降低(P<0.05),具體錶現為 CN, NC 和 NN 組雄性子代血清 TG 增加率分彆降低至 CC 組的46.4%,16.7%和7.7%,而相應雌性子代血清 TG 增加率分彆降低至 CC 組的20.6%,4.0%和8.4%。與 CC 組相比,慢性刺激前,NN 組雌、雄性子代血清 TCH 分彆下降40.5%和21.9%(P<0.01);慢性刺激後,雌性子代 TCH 增長率升高49.7%(P<0.05)。結論孕期尼古丁暴露緻大鼠神經內分泌代謝編程改變具有跨代遺傳效應,且具有一定的性彆和親源性差異。
목적:탐토잉기니고정폭로소치궁내발육지완(lUGR)자대대서신경내분비대사편정개변적과대유전효응。방법 Wistar 대서잉11 d 기매천 sc 급여니고정2 mg??kg-1지분면。자1대(F1)정상조화니고정조 lUGR 교차배대이득자2대(F2):CC 조(친씨위정상 F1)、CN 조(부위정상 F1,모위lUGR F1)、NC 조(부위 lUGR F1,모위정상 F1)화 NN 조(친씨위lUGR F1)。성년 F2급여2주빙수유영자격,수집자격전、후혈양,채용방면시제합검측혈청촉신상선피질격소( ACTH)수평, ELlSA 시제합검측피질동(CORT)수평,생화시제합검측포도당、감유삼지(TG)화총담고순(TCH)수평。결과만성자격전,NN 조웅성자대혈청 CORT 교 CC 조현저강저,위 CC 조적73.9%(P<0.05),CN 화 NC 조웅성자대혈청 TG 분별승고도 CC 조적1.43화1.52배(P<0.05),동시 CN, NC 화 NN 조자성자대혈청 TG 분별승고도 CC 조적1.71,1.80화1.81배(P<0.05);만성자격후,CC 조웅성자대혈청 CORT 증가솔위-1.67%,이 NN 조웅성자대혈청 CORT 증가솔위36.0%,NC 조웅성급 CN 조자성자대혈당현저승고,분별승고지각자 CC 대조조적1.61화1.62배(P<0.01),동시각니고정조자、웅중자대혈청 TG 증가솔균교 CC 조현저강저(P<0.05),구체표현위 CN, NC 화 NN 조웅성자대혈청 TG 증가솔분별강저지 CC 조적46.4%,16.7%화7.7%,이상응자성자대혈청 TG 증가솔분별강저지 CC 조적20.6%,4.0%화8.4%。여 CC 조상비,만성자격전,NN 조자、웅성자대혈청 TCH 분별하강40.5%화21.9%(P<0.01);만성자격후,자성자대 TCH 증장솔승고49.7%(P<0.05)。결론잉기니고정폭로치대서신경내분비대사편정개변구유과대유전효응,차구유일정적성별화친원성차이。
OBJECTIVE To investigate the transgenerational effect of neuroendocrine metabolic programmed alteration in adult intrauterine growth retardation (lUGR) offspring rats with prenatal nicotine exposure. METHODS Pregnant Wistar rats were administered daily with nicotine (2 mg.kg-1 ) by sc from gestational day 11 until delivery. F1 offspring was fed with a standard diet before four groups in F2 were set up according to the cross-mating between F1 normal adult rats and nicotine-induced lUGR adult rats. CC group was mated by F1 normal adult rats, CN group by F1 normal adult male rats and lUGR adult female rats, NC group by F1 lUGR adult male rats and normal adult female rats, while NN group was mated by F1 lUGR adult rats. F2 adult rats were subjected to a fortnight ice water swimming stimulus. Blood samples were collected before and after stress and then detected for the levels of adrenocortico-tropic hormone ( ACTH), corticosterone ( CORT), glucose, triglycerides ( TG) and total cholesterol (TCH). RESULTS Before stress, the level of serum CORT in F2 male rats of NN group was decreased to 73.9% of that of the CC group (P<0.05),while the level of serum TG in F2 male rats of CN and NC groups was increased to 1.43 and 1.52 times that of the CC group, respectively ( P<0.05). Meanwhile, the level of serum TG in F2 female rats of CN, NC and NN groups was increased to 1.71, 1.80 and 1.81 times that of the CC group, respectively (P<0.05). After stress, the serum CORT gain rate in F2 male rats of CC group was -1.67%, but was 36.0% in NN group. The serum glucose level in male NC group and in female CN group was increased to 1.61 and 1.62 times that of the corresponded CC groups, respectively (P<0.01). Furthermore, the serum TG gain rate in F2 rats of each nicotine group was decreased markedly in comparison with their corresponding controls (P<0.05), ie, the serum TG gain rates in F2 male rats of CN, NC and NN groups were decreased to 46.4%, 16.7% and 7.7% of the CC group, while the serum TG gain rates in F2 female rats of these groups were decreased to 20.6%, 4.0% and 8.4% of the CC group, respectively. Compared with CC group, TCH level of females and males in NN group was decreased by 40.5% and 21.9%(P<0.01) before stress, respectively, and the TCH gain rate of females in NN group was increased by 49.7%(P<0.05) after stress. CONCLUSION The reproductive and developmental toxicities and the neuroendocrine metabolic programming alterations induced by prenatal nicotine exposure are transgenerated to F2 offspring and these effects exhibit gender and parental differences.