胚胎期不同药物诱导大鼠隐睾模型的比较

目的 比较氟他胺(flutamide,Flu)、邻苯二甲酸二丁酯(dibutyl phthalate,DBP)、己烯雌酚(diethylstilbestrol,DES)诱导建立隐睾大鼠模型的病理表现,选择适宜研究隐睾生殖母细胞发育缺陷的动物模型.方法 SD孕鼠于妊娠12～21 d分别给予Flu(25 mg·kg-1·d-1)、DES(1.5μg·kg-1·d-1)皮下注射,DBP(500 mg·kg-1·d-1)灌胃建立隐睾模型,设立空白无干预组及玉米油皮下注射组为对照组,共5组.出生后(postnatal day,PD)20、80天获取睾丸组织,比较各药物诱导后隐睾发生率、睾丸形态学、组织学的差异.结果 Flu及DBP诱导隐睾睾丸体积PD20分别为(123.27±7.09)mm3、(117.39±8.00)mm3,PD80为(0.96±0.26)cm3、(0.79±0.28)cm3.隐睾睾丸脏器系数PD20分别为(2.27±0.09)‰、(2.26±0.09)‰,PD80分别为(1.94±0.62)‰、(2.20±0.87)‰.隐睾平均曲细精管直径(MSTD)PD20分别为(91.50±6.29)μm、(94.74±6.75)μm,PD80分别为(161.26±33.80)μm、(122.20±12.55)μm.隐睾平均曲细精管面积(MSTA)PD20分别为(6.62±0.90)×103μm2、(7.14±1.03)×103μm2,PD80分别为(2.00±1.00)×104μm2、(1.19±0.24)×104μm2.隐睾体积、脏器系数、MSTD及MSTA较对照组有明显差异(P＜0.01).Flu诱导隐睾管腔化延迟,PD20、PD80管腔中央仍可见生殖母细胞(Gonocyte,Go)残留.DES未诱导出SD大鼠隐睾,DBP组睾丸均无Go残留.结论 Flu诱导的隐睾组织中存在Go迁移障碍,曲细精管发育延迟,该模型更适宜于研究临床隐睾Go发育障碍.     

雌二醇诱导的小鼠隐睾模型的建立及形态学观察

目的 建立雌二醇诱导的小鼠隐睾模型,并对其进行组织形态学观察.方法 35只雄性新生BALB/c仔鼠随机分为正常对照组、溶剂对照组和实验组.实验组(n=15)于牛后第3～30天皮下注射17-β雌二醇4 μl(4 μg/d),溶剂对照组(n=10)皮下注射等量丙二醇,正常对照组不给予任何处理.生后第35天,观察各组睾九位置、大小,采用HE染色、透射电镜进行组织形态学观测.结果 实验组隐睾发生率100%,均为双侧隐睾,而正常对照组和溶剂对照组无隐睾发生.与对照组相比,实验组睾丸大小明显缩小,生精小管上皮数日减少,管腔消失,精母细胞和精原细胞核皱缩,支持细胞和问质细胞核仁空泡变性,未见成熟精子.结论 通过雌二醇干预法能成功诱导小鼠隐睾模型,为进一步研究隐睾的发病机制和治疗策略奠定了基础.     

胚胎期氟他胺暴露对睾丸Connexin43基因表达的影响

目的 探讨胚胎期雄激素受体阻滞剂氟他胺(flutamide,Flu)暴露对睾丸间隙连接蛋白43 (Connexin43,Cox43)基因表达的影响.方法 在胚胎期12～21 d,给予SD孕鼠氟他胺25 mg·kg-1·d-1皮下注射.应用免疫组织化学法和Real-time PCR技术,分析出生后13、15、17、20 d SD幼鼠睾丸Cox43 mRNA表达及蛋白质定位分布情况.结果 出生后(postnatal day,PD) 13、15d,Flu暴露组睾丸Cox43 mRNA和蛋白表达均明显低于正常对照组及玉米油对照组(P＜0.01);PD17 Flu暴露组与正常对照组及玉米油对照组相比,睾丸Cox43 mRNA表达差异无统计学意义(P＞0.05),而生精小管基底膜精原细胞层有Cox43蛋白异常表达分布;PD20 Flu暴露隐睾组Cox43 mRNA表达明显低于正常对照组(P＜0.05)、玉米油对照组(P＜0.05)和非隐睾组(P＜0.01),并且PD20 Flu暴露各组生精小管基底膜精原细胞层均有Cox43蛋白异常分布.结论 胚胎期Flu暴露导致睾丸Cox43mRNA转录下降,生精小管内Cox43蛋白表达分布异常.     

不同缝线行睾丸固定复位术对隐睾模型大鼠生精能力的影响

目的建立内分泌型双侧隐睾大鼠模型,通过手术复位睾丸,检测、对比应用不同缝线固定睾丸对隐睾模型大鼠生精能力的影响。方法取孕SD大鼠10只,自然分娩产仔鼠,随机选取新生雄性仔鼠40只为正常对照组,并选取80只为双侧隐睾模型组。双侧隐睾模型组大鼠从出生第3天起皮下注射17-β雌二醇,第26天观察双侧睾丸均未降入阴囊内为隐睾模型制作成功。将双侧隐睾大鼠随机分为1号丝线手术组(采用1号丝线固定睾丸)和6-0可吸收线手术组(采用6-0可吸收线固定睾丸),各40只。于日龄45 d、56 d时采集血清后处死。采用ELISA间接法测定其血清抗精子抗体(AsAb)水平。睾丸切片苏木精-伊红染色光镜下观察曲细精管生育力指数(TFI)、平均曲细精管直径(MTD)。结果 1号丝线手术组隐睾大鼠45 d、56 d时TFI、MTD水平均低于6-0可吸收线手术组(Pa<0.05);45 d、56 d时1号丝线手术组大鼠血清AsAb IgG、IgA、IgM水平均显著高于6-0可吸收线手术组(Pa<0.01)。结论采用6-0可吸收线固定睾丸可以减少AsAb的产生。     

绒毛膜促性腺激素对双侧隐睾大鼠睾丸生殖细胞凋亡的影响

目的探讨绒毛膜促性腺激素(HCG)对双侧隐睾生殖细胞凋亡的影响。方法SD雄性幼鼠于日龄22d制备双侧隐睾模型(模型组)后开始隔日肌注HCG20U,共7次。假手术组作为对照。日龄35、60d时处死取睾丸,采用生物素-dUTP/酶标亲和素(TUNEL)法检测生殖细胞凋亡情况。结果模型组双侧隐睾睾丸凋亡指数(AI)高于假手术组。35d假手术HCG治疗组AI高于假手术HCG未治疗组(P<0.05)。60d各HCG治疗组睾丸的AI高于相应HCG未治疗组,组间比较无显著差异(P>0.05)。结论隐睾时睾丸生殖细胞凋亡增加;HCG可增加生殖细胞的凋亡。     

不同日龄隐睾复位大鼠睾丸组织结构观察

目的 观察不同13龄隐睾复位大鼠睾丸组织结构的变化.方法 72只21 d雄性SD大鼠随机分为单侧隐睾组、双侧隐睾组、假手术对照组各24只.建立单、双侧隐睾动物模型.2周后行隐睾大鼠睾丸下降固定术,于日龄40、60 d处死取睾丸,采用苏木素.伊红染色光镜下观察各组大鼠精曲小管生育力指数(TFI)和平均精曲小管直径(MTD);生物素-dUTP/酶标亲和素法(TUNEL法)检测睾丸生殖细胞凋亡情况.结果 隐睾侧睾丸MTD、TFI显著低于阴囊内睾丸,而隐睾生殖细胞凋亡指数(AI)明显增高于阴囊内睾丸(P＜0.05);单侧隐睾组阴囊内睾丸TFI低于相应日龄的假手术对照组,但无统计学意义(P＞0.05).40 d时单侧隐睾组隐睾侧睾丸生殖细胞AI较双侧隐睾组低(P＜0.05),日龄60 d,各组隐睾侧睾丸AI较40 d时明显降低(P＜0.05),但单侧隐睾和双侧隐睾AI比较无统计学差异(P＞0.05).结论 实验隐睾复位大鼠睾丸AI升高,同时单侧隐睾鼠对侧睾丸组织存在不同程度的损害.随着复位时间的延长,隐睾组织的病理损害有恢复的趋势.     

人绒毛膜促性腺激素对单侧隐睾大鼠睾丸生殖细胞凋亡的影响

目的探讨人绒毛膜促性腺激素（HCG）对单侧隐睾大鼠睾丸生殖细胞凋亡的影响。方法将sD雄性大鼠40只随机分为单侧隐睾组和假手术组，各20只，于日龄21d制备单侧隐睾模型。单侧隐睾组和假手术组各又分为HCG治疗组和未治疗组。日龄22d时HCG治疗组开始肌肉注射HCG20U，隔日1次，共7次。日龄35、60d时处死大鼠，取其睾丸，采用生物素-dUTP／酶标亲和素法（TUNEL法）检测其生殖细胞凋亡水平。结果单侧隐睾组隐睾睾丸生殖细胞凋亡指数（AI）高于假手术组，但无统计学差异（P〈0．05）；单侧隐睾各组对侧睾丸生殖细胞AI高于假手术未治疗组（P〉0．05）。假手术和单侧隐睾模型HCG治疗组阴囊内睾丸生殖细胞AI高于相应未治疗组，且35d假手术组治疗组与未治疗组间差异有统计学意义（P〈0．05）。60d单侧隐睾HCG治疗组大鼠隐睾侧睾丸生殖细胞AI高于相应未治疗组，但无统计学差异（P〉0．05）。结论单侧隐睾时不仅患侧睾丸生殖细胞凋亡增加，而且隐睾对侧阴囊内睾丸生殖细胞凋亡也增加；HCG的应用可加重睾丸生殖细胞凋亡，且停用后仍存在着一些不可逆的病理损害，故临床应用HCG要慎再，应尽早手术治疗。     

冷诱导RNA结合蛋白在小鼠隐睾中的表达及与生精细胞损害的关系

目的 探讨冷诱导RNA结合蛋白(cold inducible RNA-binding protein,CIRP)在小鼠隐睾睾丸中的表达,及其与隐睾生精细胞损害的关系.方法 雄性BALB/c小鼠20只用手术的方法建立左侧隐睾模型,分别于术后第7天和第10天取双侧睾丸称重,光镜下观察睾丸组织学变化,RTPCR法检测睾丸CIRP mRNA的表达水平,Western-blot检测睾丸CIRP蛋白的表达水平,并用Annexin V-FITC/PI双染流式细胞仪检测生精细胞凋亡.结果 CIRP强表达于正常小鼠睾丸中,隐睾模型建立后,隐睾睾丸CIRP mRNA和蛋白的表达水平均明显降低(P<0.05),术后第10天隐睾睾丸CIRP表达水平明显低于第7天(P<0.05).同时隐睾侧睾丸重量较对侧睾丸明显减轻(P<0.05),术后第10天对侧睾丸重量明显重于第7天(0.102±0.006)g比(0.080±0.005)g(P<0.05);而术后第7天和第10天隐睾睾丸重量相比,(0.072±0.007)g比(0.062±0.004)g(P>0.05),差异无统计学意义.另外生精细胞的凋亡明显增加(P<0.05),术后第10天隐睾侧睾丸的生精细胞凋亡率明显高于第7天(29.2%±1.3%)比(20.2%±1.6%)(P<0.05);而对侧睾丸生精细胞凋亡率无明显差异(5.8%±1.5%)比(5.6%±1.8%)(P>0.05).组织切片显示隐睾侧睾丸生精上皮变薄,生精细胞排列紊乱.结论 小鼠隐睾中CIRP的表达明显降低,CIRP表达的降低可能在隐睾生精细胞损害中起着重要的作用.     

己烯雌酚建立尿道下裂大鼠模型的实验研究

目的　尝试用己烯雌酚 (DES)建立尿道下裂大鼠模型。方法　孕鼠 2 0只 ,随机分成 2组 :生理盐水对照组 (CG) 10只 ,DES组 10只。在大鼠怀孕 12～ 17d期间 ,每组每天分别给予管喂生理盐水 1.5ml/d ,DES 10 0 μg·kg-·d-1。待孕大鼠分娩完毕 ,即对新生大鼠计数并在放大镜及解剖显微镜下观察雄性新生鼠的阴茎包皮外观、尿道口位置、排尿情况 ,测量肛生殖距离 (AGD)和称体重。结果　①DES成功诱导出了雄性大鼠尿道下裂畸形 ,对照组大鼠的生殖器未见异常改变 ;②DES组新生大鼠的AGD缩短 ,但无统计学差异 ,DES组体重明显减轻 ,有显著统计学差异。结论　①成功建立的尿道下裂大鼠模型 ,较国外尿道下裂小鼠更直观 ,更规范 ;②尿道下裂大鼠模型可以为研究尿道下裂病因学和防治措施提供基础。     

DEHP诱导的隐睾鼠胰岛素样因子3基因CpG岛甲基化状态研究

目的 研究胰岛素样因子3(insulin-like factor 3,INSL3)基因在邻苯二甲酸二已酯(DEHP)致小鼠隐睾中DNA甲基化的状态.方法 运用"MethPrimer"软件对INSL3基因进行分析.预测CpG岛,通过甲基化特异性PCR(methylation-specific PCR,MS-PCR)检测INSL3基因CpG岛的甲基化状况,并应用RT-PCR检测INSL3基因在正常组与实验组睾丸组织中的表达情况.结果实验组INSL3基凶第一外显子区存在CpG岛甲基化;实验组INSL3基因mRNA表达显著下降.结论 INSL3基因第一外显子区CpG岛的异常甲基化导致INSL3在隐睾鼠睾丸中表达降低,可能与隐睾的发生密切相关.     

Prenatal alcohol exposure and cryptorchidism

AIM: A recently published study reported markedly increased risk of cryptorchidism among boys whose mothers had an average gestational alcohol intake of five or more drinks per week. The aim of this study is to follow up on this finding by estimating the association between prenatal alcohol exposure and persistent cryptorchidism. METHODS: We used prospectively collected information on prenatal exposures and obstetric information on the birth of 5716 boys, collected from 1984 to 1987. During the 16-19 years of follow-up in a nationwide patient register, 270 cases of cryptorchidism were diagnosed and 185 of these boys underwent orchiopexy. RESULTS: No positive association between the mothers' average weekly alcohol consumption and persistent cryptorchidism was observed. Binge drinking was nonsignificantly associated with an excess risk of orchiopexy (adjusted RR = 1.4; 95% CI 0.9-2.1), but not with having a diagnosis of cryptorchidism without orchiopexy. CONCLUSIONS: Mothers' average weekly alcohol intake was not associated with persistent cryptorchidism, but binge drinking may be a risk factor.     

Cardiovascular malformations induced by prenatal exposure to phenobarbital in rats

The effects of prenatal exposure to phenobarbital (PB) on the cardiovascular system were examined in rat fetuses and pups. PB was administered at a dose of 80 or 120 mg/kg/day by gavage to Sprague Dawley (SD) rats on two consecutive gestational days (GD): 7-8, 8-9, 9-10, or 10-11. Fetuses were examined for cardiovascular malformations on GD 20. In addition, pups were examined for PB-induced cardiovascular malformations. Incidences of ventricular septal defect (VSD), overriding aorta, double outlet right ventricle and transposition of great arteries were significantly increased in the fetuses whose dams were administered PB at 120 mg/kg on GD 8-9, 9-10 or 10-11. GD 8-11 was the critical period for the cardiovascular malformations associated with administration of PB in rats. Various types of cardiovascular malformations were detected in pups from the PB-administered dam. Severe cardiovascular malformations induced by PB caused deaths on early postnatal days. However, slight malformations such as isolated VSD persisted until weaning, and did not affect postnatal viability.     

维甲酸诱导大鼠脊髓脊膜膨出动物模型的建立及相关蛋白表达的研究

目的 探索利用全反式维甲酸(ATRA)诱导大鼠胎鼠脊髓脊膜膨出(MMC)建立神经源性膀胱(NBD)的大鼠动物模型,并观察相关病理表现及蛋白表达.方法 探索在不同给药时间及不同ATRA剂量下,大鼠胎鼠MMC的发生情况,得到最佳诱导致畸时间及ATRA剂量,建立动物模型;所得胎鼠分为MMC组(胎鼠出现MMC,不合并其他严重畸形)、RA组(胎鼠外观正常,无明显畸形)、OIL组(母鼠同期灌胃2ml橄榄油,得到正常胎鼠).观察该模型胎鼠相关组织的病理表现,并通过免疫组化方法测定脊髓组织GFAP、膀胱组织α-SMA、膀胱tubulin-β-Ⅲ和nNOS表达情况.结果 在母鼠孕10d(E10)以120 mg/kg的剂量灌胃ATRA能获得最佳建模效果;MMC组胎鼠脊髓组织病理表现存在异常,膀胱组织病理表现基本正常;MMC组胎鼠脊髓组织GFAP蛋白表达(5.5±1.6)×1 04,较RA组的(2.5±2.0)×104增加,膀胱组织α-SMA蛋白无明显差异,MMC组膀胱组织tubulin-β-Ⅲ和nNOS蛋白表达分别为(22.4±2.7)×104、(16.1±4.1)×104,较RA组的(28.4±8.3)×104、(25.6±7.1)×104减少.结论 ATRA能诱导大鼠胎鼠产生MMC,得到MMC相关NBD动物模型;其MMC胎鼠具有典型的脊髓损伤表现,尽管膀胱肌层发育正常但存在明显的神经分布异常.     

The effect of in utero insulin exposure on tissue iron status in fetal rats.

Newborn infants of diabetic mothers have serum biochemical signs of iron deficiency in cord blood directly related to elevations of cord erythropoietin and Hb concentrations. In sheep, chronic fetal hyperinsulinemia results in fetal hypoxemia, expansion of the red cell mass, and decreased iron concentrations, most likely due to increased iron utilization for Hb synthesis. To determine whether fetal insulin exposure also results in reduced tissue iron concentrations, we measured liver, skeletal muscle, small intestine, heart, and brain iron concentrations in newborn rat pups after s.c. fetal injection of insulin or diluent alone on d 19 of gestation. The fetuses of 11 pregnant rats were exteriorized, injected with 2 U neutral protamine Hagedorn insulin or diluent, replaced in utero, and delivered on d 22. To determine dose dependency, the fetuses of six pregnant rats were injected with 3 U of longer-acting protamine zinc insulin and delivered on d 21. At delivery, the insulin-treated groups had higher birth weights than the placebo-treated group, although plasma insulin concentrations were not different. The 2 U neutral protamine Hagedorn insulin-treated fetuses had significantly lower mean +/- SEM liver iron concentrations than the control fetuses (910 +/- 34 versus 1014 +/- 43 micrograms/g dry tissue weight; p less than 0.05), but had similar skeletal muscle iron concentrations. The 3 U protamine zinc insulin-treated fetuses had significantly lower liver and skeletal muscle iron concentrations compared to control and to 2 U neutral protamine Hagedorn insulin-treated fetuses (p less than 0.05). No differences in small intestine, heart, or brain iron concentrations were seen among groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Family studies in fetal phenytoin exposure

Sixty-two families with fetal diphenylhydantoin exposure were studied during two or more pregnancies. In 15 of these families at least one of the exposed children had some of the physical effects of DPH exposure ("affected" families); in the remaining 47 families no exposed child was affected ("unaffected" families). Review of 62 family histories and pedigrees was not helpful in differentiating these two groups for counseling purposes. However, mothers who had one affected child appeared to be at much higher risk for having subsequent affected children (9 of 10) if phenytoin use was continued through future pregnancies than were mothers whose first-born child was unaffected despite being exposed to phenytoin during the pregnancy (5 of 52 among all families, or 1 of 48 when only children exposed throughout the entire pregnancy were included). The difference between families with the first exposed child affected and first exposed child unaffected was highly statistically significant (p less than 0.0001). School and learning problems and developmental or mental retardation were present in both groups, and significantly more frequently in affected families. Physical and growth abnormalities were noted in both affected and unaffected family groups, also at a significantly higher rate in affected families.     

Effects of early embryonal exposure to dexamethasone on malformations of neural-crest derivatives induced by nitrofen in rats

Prenatal corticosteroids reverse to some extent lung and heart hypoplasia in nitrofen-exposed rat pups. The present study examines the effects of early exposure to dexamethasone on the neural crest-related malformations of the cardiovascular system, thymus, parathyroids, and thyroid observed in this model. Pregnant rats were exposed on gestational day 9.5 to either 100 mg 2-4-dichlorophenyl-p-nitrophenyl ether (nitrofen) alone or followed on days 10.5 and 11.5 by 0.4 mg/kg dexamethasone (dexa) i.p. Controls were treated with either oil alone or oil+dexa alone. The fetuses were recovered near term and diaphragmatic, lung, heart, and thymic malformations were sought after dissection. The parathyroids and thyroid were histologically investigated. Control fetuses had no malformations whereas 68% of nitrofen and 65% of nitrofen + dexa fetuses had congenital diaphragmatic hernias (CDH). Heart-outflow tract and pharyngeal artery anomalies were seen in 62% and 61%, respectively in both groups. Heart hypoplasia, which was severe in the nitrofen group, was fully reversed in nitrofen+dexa pups. In contrast, thymic hypoplasia was of similar severity in both groups. The hypoplastic thymus was malformed in 29% and 39%, the parathyroids in 50% and 41%, and the thyroid in 25% and 16% of fetuses, respectively. These differences were not significant. Early exposure to dexa in rat fetuses previously treated with nitrofen thus does not produce any benefit on the incidence or severity of malformations of the cardiac outflow tract and pharyngeal derivatives that accompany CDH in rats exposed to nitrofen. However, even administered so early, this medication prevents heart hypoplasia, suggesting a favorable effect on early heart organogenesis.     

The contribution of fetal drug exposure to temperament: potential teratogenic effects on neuropsychiatric risk

BACKGROUND: Preliminary evidence indicates that fetal drug exposure may be associated with alterations in temperament. However, studies often do not dissociate the potential effects of drug exposure from other perinatal or environmental factors that could influence temperament phenotypes. METHODS: High risk children (n = 120) were followed from birth to 6 months of age to determine the effects of fetal drug exposure on temperament, after controlling for the child's gender, gestational age, medical morbidity, ethnicity, and maltreatment as well as the mother's stress, income adequacy, and quality of caregiving. Methods included medical chart review, questionnaires, and videotapes of mother-child interaction. RESULTS: Preliminary analyses indicated that fetal drug exposure was associated with both distractibility and intensity of children's responses to the environment at 6 months of age. After adjusting for potentially confounding variables, drug exposure accounted for 12% of the variance in distractibility but was not a significant predictor in the regression model for intensity. CONCLUSIONS: Findings suggest that drug-exposed children may experience difficulty sustaining their focus of attention and be more easily distracted by environmental stimuli than non-drug-exposed children. Results converge with previous research to implicate cortical hyperarousal, stemming from teratogenic effects on the dopaminergic system during fetal development.     

Effects of prenatal methamphetamine exposure on fetal growth and drug withdrawal symptoms in infants born at term

To determine fetal growth and the incidence of withdrawal symptoms in term infants exposed to methamphetamine in utero, we retrospectively identified neonates whose mothers used methamphetamine during pregnancy and matched them to unexposed newborns. Exclusion criteria included multiple and preterm gestations. Although there were no differences in infant growth parameters between the methamphetamine-exposed and methamphetamine-unexposed neonates, methamphetamine exposure throughout gestation was associated with decreased growth relative to infants exposed only for the first two trimesters. In addition, there were significantly more small for gestational age infants in the methamphetamine group compared with the unexposed group. Methamphetamine-exposed infants whose mothers smoked had significantly decreased growth relative to infants exposed to methamphetamine alone. Withdrawal symptoms (as determined by a previously reported scoring system) requiring pharmacologic intervention were observed in 4% of methamphetamine-exposed infants. These preliminary findings indicate that methamphetamine use is associated with growth restriction in infants born at term.     

外源性甲状腺素对胎儿酒精效果出生后大鼠小脑发育的改善作用

目的 研究胎儿酒精效果对大鼠小脑皮质中脑源性神经营养因子(BDNF)和酪氨酸激酶B(TrkB)的影响及外源性甲状腺素(T4)的效应.方法 选择怀孕第6天的SD孕鼠随机分为酒精组、正常组、酒精 + T4组以及代理母鼠组.酒精组孕鼠摄取1 475 J/d的酒精;正常组孕鼠摄取与酒精组同热卡的奶粉;酒精 + T4组孕鼠摄取与酒精组同量的酒精,同时皮下注射5 μg/(kg·d)甲状腺素;代理母鼠组摄取正常鼠食.酒精组、正常组、酒精 + T4组母鼠分娩6 h后处死采血,测试血中酒精浓度和甲状腺素含量.三组仔鼠由代理母鼠养育,并分别于生后第7、14、21、28、60、90天麻醉处死,采用免疫组织化学染色法,观察小脑皮质中BDNF和TrkB阳性浦肯野细胞的分布及形态,并测算小脑4/5小叶中单位面积所含的BDNF或TrkB阳性浦肯野细胞数.结果 三组18只母鼠(每组6只)及其所生仔鼠中144只(每组均选择48只)纳入分析.酒精组、酒精 + T4组母鼠的血液酒精浓度高于正常组,差异有统计学意义(P ＜ 0.05);酒精 + T4组母鼠血液甲状腺素含量高于酒精组,差异有统计学意义(P ＜ 0.05).酒精 + T4组仔鼠从第14天开始,小脑皮质中出现分布及形态与正常组类似的BDNF和TrkB阳性浦肯野细胞,酒精组仔鼠小脑皮质中始终未出现BDNF和TrkB阳性浦肯野细胞.酒精 + T4组仔鼠小脑中BDNF和TrkB阳性浦肯野细胞数,从第14天起与正常组无差异(P ＞ 0.05);酒精组仔鼠小脑中BDNF和TrkB阳性浦肯野细胞数,从第28天起较正常组及酒精 + T4组显著减少(P ＜ 0.01),并持续到第90天.结论 外源性甲状腺素能促进小脑皮质中BDNF和其特异性受体TrkB的合成,促进BDNF-及TrkB-阳性浦肯野细胞的发育,进而改善胎儿酒精效果致低甲状腺素所引起的小脑发育障碍.