甲基汞的行为致畸效应

目的　探讨胚胎期甲基汞暴露对大鼠仔代的行为致畸效应。方法　 3月龄Ｗｉｓｔａｒ雌性大鼠受孕后随机分为 4组 ,采用甲基汞 (0 0 0、0 0 1、0 0 5、2 0 0ｍｇ·ｋｇ- 1 ·ｄ- 1 )于妊娠 6～9ｄ灌胃染毒。 2 8只孕鼠妊娠 19ｄ时进行传统致畸试验。 2 4只孕鼠自然分娩 ,观察 2 0 1只仔鼠出生后的早期神经行为发育 ;79只仔鼠出生 7周时进行迷宫测试 ;32只仔鼠出生 10周时进行自动化操作行为测试。分娩 5周的 2 4只母鼠及出生10周的 2 4只仔鼠进行脑组织检查。结果　胚胎期甲基汞暴露对大鼠的母体毒性十分微弱 ;但低剂量就对胎仔体重及尾长…     

豆腐果甙的神经行为致畸效应

目的　应用神经行为畸胎学方法评价豆腐果甙对大鼠仔代的神经行为的毒性。方法　健康 3月龄Ｗｉｓｔａｒ雌性大鼠受孕后期随机分为 4组 ,于妊娠后 6～ 15ｄ采用 0、2 7、2 70、135 0ｍｇ·ｋｇ- 1 ·ｄ- 1 剂量豆腐果甙连续灌胃染毒 ,观察 17只孕鼠妊娠及分娩后的变化 ,以及 16 0只仔鼠出生后的早期神经行为发育指标 ;随机选择 32只仔鼠于 10周龄时进行自动化操作行为测试。此外 ,对 10周龄的 2 4只仔鼠进行脑组织检查。整个实验采用双盲法。结果　未观察到胚胎期不同剂量豆腐果甙暴露对大鼠明显的母体毒性 ;3个暴露组仔鼠的体重增长、早期…     

弓形虫RH强毒株对大白鼠中枢神经系统影响的研究

目的 探讨弓形虫感染对中枢神经系统的影响.方法 对不同孕期的大鼠腹腔感染弓形虫,观察其产仔及仔鼠生长存活情况,用迷宫实验检测仔鼠学习分辨及记忆能力,并对死亡的仔鼠大脑进行病理切片. 结果 早期感染弓形虫者其仔鼠在迷宫测试中,学习分辨能力及记忆能力显著低于对照组(P＜0.001);不同孕期感染各组学习成绩超过对照组算术均数3.21天的仔鼠数中,早期感染组所产仔鼠与对照组差异有显著性(P＜0.05);早期、中期感染组所产仔鼠在学习中的电击次数超过对照组算术均数4.41次的仔鼠数与对照组差异呈显著性(P＜0.05);晚期感染组其仔鼠6～7周死亡数显著高于对照组(P＜0.01)且大脑病理切片结果显示:大脑皮质空洞,大量嗜酸性细胞增生、集聚,提示寄生虫感染.结论 不同孕期感染弓形虫均可导致胎儿的先天性感染,造成中枢神经系统的损害.     

1-(2-氯)苯基-9-丁基-β-咔啉对小鼠的神经毒性作用

目的: 探讨去氢骆驼蓬碱衍生物1-(2-氯)苯基-9-丁基-β-咔啉(简称"DH-330")对小鼠神经行为损伤的影响及可能机制,为系列衍生物的开发提供依据。方法: 将昆明小白鼠随机分为4组,分别为空白对照组(0.9% NaCl溶液)、低剂量组(69.44 mg·kg^-1 DH-330)、中剂量组(208.33 mg·kg^-1 DH-330)和高剂量组(347.22 mg·kg^-1 DH-330),连续灌胃给药28 d,采用Morris水迷宫实验测试神经行为;通过免疫吸附测定法(ELISA)测定小鼠脑组织中ROS、GSH、MAO、AChE、5-HT含量,同时采用透射电镜对小鼠海马组织超微结构进行观察。结果: Morris水迷宫实验:高剂量DH-330对小鼠的空间学习记忆能力造成影响,主要表现为高剂量组小鼠的逃避潜伏期及总行程显著长于对照组(P＜0.05),而穿台次数及靶象限停留时间显著少于对照组(P＜0.05)。生化指标结果:与对照组比较,DH-330高剂量组小鼠脑内ROS、5-HT水平显著升高(P＜0.05);GSH、AChE、MAO含量显著降低(P＜0.05)。海马超微结构:高剂量DH-330可导致海马组织中细胞结构损伤,主要表现为异染色质多黑、线粒体出现空泡化等现象。结论: DH-330可致小鼠神经行为系统损伤,其机制可能是通过抑制小鼠脑内AChE、MAO及GSH含量,促使ROS、5-HT水平升高,导致氧化平衡状态改变及单胺类神经递质含量升高,从而诱导神经行为毒性。     

出生后接触氰戊菊酯对仔鼠神经行为发育及学习记忆的影响

目的 观察出生后早期有限次数氰戊菊酯(FEN)染毒对ICR仔鼠神经发育毒性影响,尤其是对成年后学习记忆的影响.方法 仔鼠自出生第3天开始腹腔注射染毒,隔天一次,连续6次,分5、0.5和0.05 mg/kg 3个FEN染毒组及二甲基亚枫(DMSO)和生理盐水2个对照组,DMSO 11只,其余各组均为16只.观察仔鼠的一般生理和神经行为发育情况,进行旷场实验、平衡木实验、学习记忆功能测试--包括新物体识别、水迷宫.结果 染毒期间,仔鼠躯体感觉运动发育受影响,但至青年期在平衡木测试中,各组已无差异;在旷场实验中,反映自发性活动和焦虑情绪的指标在各组间均无差异;成年后在Morris水迷宫空间探索实验中,高剂量组小鼠在60 s内穿越平台次数减少(P＜0.05).结论 出生后早期有限次数接触低剂量FEN在染毒期间会影响仔鼠躯体感觉运动功能发育,发育至青年期,小鼠的感觉运动功能得以恢复;但出生后早期接触低剂量氰戊菊酯,会影响小鼠成年后的空间记忆能力.     

白苏油改善自然衰老小鼠学习记忆的可能机制

目的:研究白苏油改善自然衰老小鼠学习记忆的可能机制.方法:使用超临界CO2萃取法提取的白苏油,按照0.8,1.6,2.4 g·kg-1·d-1的剂量给22月龄的老年小鼠灌胃给药,qd,连续灌胃10周后,使用开场实验,避暗实验和通道式水迷宫实验方法测定小鼠的学习记忆功能,再测定小鼠脑组织中抗氧化指标[超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、丙二醛(MDA)]和部分单胺类神经递质等指标[一氧化氮(NO)、乙酰胆碱酯酶(AchE)、单胺氧化酶(MAO)、多巴胺(DA)].实验同时设立22月龄老年小鼠的模型对照组和5月龄青年小鼠的正常对照组,均灌胃给予等体积的菜籽油(白苏油的溶剂).结果:与正常对照(青年小鼠)比较,模型组(老年溶剂对照组)小鼠的学习和记忆能力显著降低(P＜0.01),脑组织中SOD,GSH-Px和CAT酶活性均显著降低(P＜0.01),MDA含量显著增加(P＜0.01),脑组织DA和NO含量明显减少(P＜0.01),AchE和MAO活性明显增加(P＜0.01).白苏油能逆转老年小鼠的学习和记忆能力的下降,以及小鼠脑组织中抗氧化酶(SOD,GSH-Px)和单胺类神经递质[NO,AchE,MAO,DA]等相关指标的改变,并呈现一定的剂量依赖性(P＜0.05或P＜0.01).结论:白苏油改善自然衰老小鼠的学习记忆能力与其增强抗氧化酶的活性和提高部分单胺类神经递质的含量有关.     

健脾生血颗粒对围产期大鼠的毒性研究

目的:考察健脾生血颗粒对围产期大鼠的毒性作用。方法:将受孕大鼠按体质量随机分为阴性对照组和健脾生血颗粒低、中、高剂量组(0.77、2.31、6.93 g/kg),每组21只,从妊娠第15天开始至分娩后第21天止每天ig相应药物1次。观察健脾生血颗粒对母代大鼠一般毒性和生育能力的影响,对F1代仔鼠运动能力、学习记忆能力、生育能力以及对F2代仔鼠早期发育能力的影响。结果:对母代的毒性作用方面,健脾生血颗粒高剂量组母代大鼠妊娠天数较阴性对照组显著延长(P<0.05),给药初期体质量显著降低(P<0.01)。对子代的毒性作用方面,健脾生血颗粒高剂量组F1代仔鼠初生体质量较阴性对照组显著降低(P<0.05),第4、5次发现水下平台时间较阴性对照组显著缩短(P<0.01);对F1代仔鼠生育能力及F2代仔鼠早期发育能力均未见明显影响(P>0.05)。健脾生血颗粒中、低剂量组子代大鼠各指标均未见受到明显影响。结论:健脾生血颗粒对母代及子代大鼠均未见毒性反应的剂量为2.31 g/kg。     

褶合曲线分析法同时测定氯麻滴鼻剂中两组分的含量

盐酸丁螺环酮是一种新抗焦虑药，大鼠致畸胎试验结果表明，给药剂量达到７５ｍｇ／ｋｇ时，产生一定的母体毒性和胚胎毒性。但未同凶致畸胎作用。对仔鼠出生存活率、出生生长发育、学习能力、神经行为发育和生殖能力等无影响，无作用剂量水平为２ｍｇ／ｋｇ。     

蒲公英总黄酮提取液对衰老模型小鼠脑组织单胺氧化酶及单胺类神经递质含量的影响

目的:探讨蒲公英总黄酮提取液对衰老模型小鼠脑组织单胺氧化酶(MAO)及单胺类神经递质含量的影响.方法:采用小鼠注射D-gal制成衰老模型,蒲公英总黄酮提取液灌胃30d,测定小鼠脑组织MAO活性及单胺类神经递质的含量.结果:蒲公英总黄酮提取液能降低衰老模型小鼠脑组织内MAO活性(P＜0.05),提高去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)含量(P＜0.05).结论:蒲公英总黄酮提取液可降低衰老模型小鼠脑组织MAO活性并能提高单胺类神经递质的含量,具有一定的抗衰老作用.     

钙蛋白酶抑制剂Ⅲ MDL 28170对大鼠甲基汞急性神经毒性的拮抗作用

目的为寻找治疗甲基汞急性中毒作用药物新靶点,探讨钙蛋白酶抑制剂ⅢMDL28170对甲基汞急性神经毒性的拮抗作用。方法大鼠随机分为正常对照组、MDL28170(50mg.kg-1,ip)对照组、甲基汞(10mg.kg-1,ig)中毒模型组与MDL28170干预组(同时ig甲基汞和ip MDL28170)。Morris水迷宫检测大鼠学习记忆能力,免疫组织化学法观察脑μ-钙蛋白酶免疫阳性神经元,Western蛋白印迹法检测脑μ-钙蛋白酶表达,TUNEL法观察脑神经元凋亡,免疫荧光染色法观察脑皮质神经元微管相关蛋白2(MAP2)含量。结果大鼠ig给予甲基汞3或7d,中毒模型组出现神经系统损害行为学表现,水迷宫逃避潜伏期明显延长(P<0.01);脑皮质神经元内μ-钙蛋白酶的表达和活性明显升高(P<0.01);脑皮质神经元凋亡显著增加(P<0.01);神经元MAP2含量明显降低。同时给予MDL28170可明显减轻上述改变。结论μ-钙蛋白酶可能参与甲基汞中毒导致的神经细胞凋亡。MDL28170可明显抑制甲基汞的神经毒性损害,可能对甲基汞中毒具有治疗作用。     

Effects of maternal exposure to picrotoxin during lactation on physical and reflex development,square crossing and sexual behavior of rat offspring

The effects of maternal exposure during the first 10 days of lactation to picrotoxin (0.75 mg/kg sc) on maternal behavior, offspring physical and neurobehavioral development as well as sexual behavior were studied. Results showed that (1) dam food and water consumption, maternal behavior and body weight were not different between control and experimental animals, (2) male and female pup body weight and the development of physical landmarks did no differ between control and experimental groups, (3) negative geotaxis was improved in female experimental offspring and palmar grasp reflex did not differ between groups, (4) at 75 days of age the square crossing by female rats of the experimental group was increased in relation to the control group; no differences were observed between male control and experimental animals, (5) male experimental rats exhibited a significant increase in the number of mounts, intromissions and ejaculations parallel to a decrease in latency to first mount, intromissions and ejaculation as well as in the latencies of first postejaculatory mount and intromission and (6) the intromission frequency per minute (hit rate) was increased in these animals. These results suggest that postnatal exposure to picrotoxin improved the sexual behavior of rats. Three hypotheses were proposed to explain the mechanisms underlying this effect: (1) the development of subsensitivity of GABAergic receptors, (2) an interference with early receptor development or (3) with neurotransmitter balance, mainly involving the dopaminergic system.     

Developmental and neurobehavioral effects of perinatal exposure to polychlorinated biphenyls in mice

Because behavioral deficits associated with gestational exposure to polychlorinated biphenyls (PCBs) have been a concern, we studied the developmental and neurobehavioral effects of perinatal exposure to Aroclor 1254 (A1254), a commercial mixture of PCBs, in mice. The PCB mixture (A1254; 0, 6, 18, and 54 mg/kg body weight) was administered to pregnant mice (C57BL/6Cr) every 3 days by gavage from gestational day (GD) 6 to postnatal day (PND) 20. Compared with the control, treatment with A1254 did not alter the maternal body weight during the gestation and lactation periods. The body weight of the offspring did not differ among treatments. To assess the effects on offspring following such exposure, physical and neurobehavioral development (i.e., pinna detachment, hair growth, eye opening, incisor eruption, grasp reflex, righting reflex, walking, negative geotaxis, and cliff avoidance) was observed before weaning. At PND 7, poor adult-like responses in negative geotaxis were observed in all exposed groups. When the offspring were at 8-week old, the PCB-treated (18 mg/kg body weight) mice showed a decreased walking speed in the open-field test, and a prolonged time to reach the platform in the water maze test. Spontaneous locomotion activity was not affected by PCB exposure at 9 weeks . These results showed that perinatal exposure to PCBs produces several behavioral alterations in mice. Although dose-dependent changes were not observed, the neurobehavioral effects such as a decreased walking speed in the open-field test and a prolonged time to reach the platform in the water maze test remained in adulthood after the seeming recovery from the transient delay in development before weaning.     

Neurobehavioral effects of combined prenatal exposure to low-level mercury vapor and methylmercury

We evaluated the effects of prenatal exposure to low-level mercury (Hg(0)) or methylmercury (MeHg) as well as combined exposure (Hg(0) + MeHg exposure) on the neurobehavioral function of mice. The Hg(0) exposure group was exposed to Hg(0) at a mean concentration of 0.030 mg/m(3) for 6 hr/day during gestation period. The MeHg exposure was supplied with food containing 5 ppm of MeHg from gestational day 1 to postnatal day 10. The combined exposure group was exposed to both Hg(0) vapor and MeHg according to above described procedure. After delivery, when their offspring reached the age of 8 weeks, behavioral analysis was performed. Open field (OPF) tests of the offspring showed an increase and decrease in voluntary activity in male and female mice, respectively, in the MeHg exposure group. In addition, the rate of central entries was significantly higher in this group than in the control group. The results of OPF tests in the Hg(0) + MeHg exposure group were similar to those in the MeHg exposure group in both males and females. The results in the Hg(0) exposure group did not significantly differ from those in the control group in males or females. Passive avoidance response (PA) tests revealed no significant differences in avoidance latency in the retention trial between the Hg(0), MeHg, or Hg(0) + MeHg exposure group and the control group in males or females. Morris water maze tests showed a delay in the latency to reach the platform in the MeHg and Hg(0) + MeHg exposure groups compared with the control group in males but no significant differences between the Hg(0), MeHg, or Hg(0) + MeHg exposure group and the control group in females. The results of OPF tests revealed only slight effects of prenatal low-level Hg(0) exposure (0.03 mg/m(3)), close to the no-observable-effect level (NOEL) stated by the WHO (0.025 mg/m(3)), on the subsequent neurobehavioral function. However, prenatal exposure to 5 ppm of MeHg affected exploratory activity in the OPF test, and, in particular, male mice were highly sensitive to MeHg. The MeHg and Hg(0) + MeHg exposure groups showed similar neurobehavioral effects. Concerning the effects of prenatal mercury exposure under the conditions of this study, the effects of MeHg exposure may be more marked than those of Hg(0) exposure.     

Behavioural effects of prenatal metallic mercury inhalation exposure in rats

The effects of administration by inhalation of metallic mercury vapour (Hg⁰) to pregnant rats, approximately corresponding to doses of 0.2 mg Hg⁰/kg /day (high dose) or 0.07 mg Hg⁰/kg/day (low dose), on the developmental and behavioural repertoire of the offspring were studied. Exposure occurred during days 11–14 plus 17–20 of gestation. The dose levels were selected so as not to induce maternal toxicity. Maturation variables such as surface righting, negative geotaxis, pinna unfolding, and tooth eruption revealed no differences between Hg⁰-treated offspring and controls. Tests of spontaneous motor activity showed that the Hg⁰-treated offspring were hypoactive at 3 months of age but hyperactive at 14 months. In spatial learning tasks the prenatally exposed offspring showed retarded acquisition in the radial arm maze but no differences in circular swim maze. A simple test of learning, habituation to a novel environment (activity chambers), indicated a reduced ability to adapt. These data suggest that prenatal exposure to Hg⁰ vapour results in similar behaviour changes in the offspring as reported for methylmercury.     

Persistent neurobehavioral effects of early postnatal domoic acid exposure in rats

Domoic acid (DA) is a marine biotoxin, produced by the diatom Pseudo-nitzchia spp., which has been shown to cause cognitive impairment in adults who are exposed via contaminated seafood. The neurobehavioral consequences of developmental exposure are much less well understood. In a previous study, we showed that a single prenatal exposure to DA in rats at mid-gestation caused neurobehavioral changes that persist into adulthood including increased susceptibility to the benchmark amnestic drug scopolamine. In the current study, we examined the lasting neurobehavioral consequences of DA exposure on the first day of postnatal life, a time in rats marking the completion of the major phase of neuroproliferation and corresponding to week 24 of human gestation. The effects of DA exposure at doses from 0.025–0.1 mg/kg (s.c.) twice per day on each of postnatal days 1 and 2 were compared with vehicle-treated controls and rats treated by the same protocol with 1 mg/kg of kainic acid. Following kainic acid exposure, a sex-selective effect was seen with females but not males showing a significant slowing of response latency in the radial-arm maze. The high DA dose of 0.1 mg/kg was quite toxic causing lethality in all of the offspring exposed and this group was excluded from further analysis. When the offspring in the 0.05 mg/kg DA dose group were tested, significant hypoactivity in the Figure-8 maze was observed during adolescence. No significant DA effects were seen in response latency or choice accuracy on the radial-arm maze during either acquisition or with challenge of the amnestic drug scopolamine. Early postnatal DA exposure in the rat can be lethal and sublethal exposure can cause neurobehavioral effects manifest in modest hypoactivity during the adolescent period. However, the sublethal persistent neurobehavioral toxicity appears to be less pervasive than reported effects following DA administered mid-gestation.     

Methylmercury effects on reproduction and offspring size at birth

This article describes a study of the toxic, reproductive, and developmental effects of chronic methylmercury (MeHg) exposure in Macaca fascicularis monkeys. Adult and infant monkeys were studied using procedures to assess maternal and newborn blood Hg concentrations, menstrual cyclicity, conception rate, reproductive outcome, maternal toxicity, and offspring size at birth. Maternal intakes of 0, 50, 70, or 90 μg/kg/d MeHg hydroxide were studied. Maternal blood Hg concentrations reached equilibrium by 10 weeks of exposure. The half-life of blood Hg for adult females ranged from 15 to 40 days ( ) and did not vary with dose. Maternal MeHg exposure did not affect the length of the menstrual cycle or the conception rate. Maternal MeHg exposure did significantly reduce the number of viable deliveries at blood Hg concentrations above 1.5 ppm. Maternal blood Hg concentrations at delivery were significantly lower than newborn concentrations. No effect of maternal MeHg exposure on offspring size at birth was observed. Maternal toxicity was related to blood Hg concentrations above 2.0 ppm following approximately one year of exposure. Results indicate that MeHg exposure can affect reproductive outcome at levels that do not overt toxicity.     

Developmental neurotoxicity after toluene inhalation exposure in rats.

Rats were exposed to 1200 ppm or 0 ppm toluene (CAS 108-88-3) for 6 h per day from day 7 of pregnancy until day 18 postnatally. Developmental and neurobehavioral effects in the offspring were investigated using a test battery including assessment of functions similar to those in the proposed OECD TG for Developmental Neurotoxicity Study, i.e., physical development, reflex ontogeny, motor function, motor activity, sensory function, and learning and memory. The exposure did not cause maternal toxicity or decreased viability of the offspring. Lower birth weight, delayed ontogeny of reflexes, and increased motor activity in the open field was registered in the exposed offspring. Impaired cognitive function was revealed in the exposed female offspring at the age of 3.5 months, i.e., they used more time to locate the hidden platform in the Morris water maze after platform relocation. The difference was not related to poorer swimming capabilities, because swim speeds were similar to control values. The results show that exposure to 1200 ppm toluene during brain development caused long-lasting developmental neurotoxicity in rats.     

Exposure of pregnant rats to uranium and restraint stress: effects on postnatal development and behavior of the offspring

The effects on postnatal development and behavior were assessed in the offspring of female rats concurrently exposed to uranium (U) and restraint stress. Adult female rats were administered uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 40 and 80 mg/(kg day) for 4 weeks before mating with untreated males, as well as during pregnancy and lactation. One-half of female rats in each group were concurrently subjected to restraint (2h/day). On gestation day 14, one-half of restrained and unrestrained rats were sacrificed in order to evaluate maternal toxicity and gestational parameters. Pups were evaluated for physical development, neuromotor maturation, and behavior. Uranium concentrations were also determined in various tissues of dams and fetuses. In all uranium-treated groups, the highest concentrations of this element were found in kidney and bone, being considerably higher than those in brain. Uranium levels in tissues of dam or fetuses were not significantly affected by restraint. No significant interactions between uranium and restraint could be observed in maternal toxicity. Moreover, no relevant effects of uranium, maternal restraint, or their combination were noted on developmental landmarks in the offspring. In the passive avoidance test, at 40 and 80 mg UAD/(kg day) restraint significantly modified passive avoidance acquisition (T1) and retention time (T2) 24h later. However, no significant differences were observed on the Morris water maze test. The results of the present study indicate that, in general terms, exposure of female rats to UAD before mating with untreated males, as well as during gestation and lactation, did not cause relevant dose-related adverse effects on postnatal development and behavior of the offspring. The influence of stress was very limited.     

奥氮平所致糖脂代谢紊乱对大鼠认知功能的影响

目的：探讨奥氮平所致糖脂代谢紊乱对大鼠认知功能的影响。方法选择健康清洁级SD雄性大鼠40只,用随机数字表法分为正常对照组和奥氮平组,每组10只。奥氮平组大鼠用奥氮平1.1 mg/kg灌胃,1次/d,共4周,复制肥胖模型;正常对照组大鼠用等体积0.9%氯化钠注射液灌胃,1次/d,共4周。灌胃期间每周测量大鼠体重。第4周灌胃结束后,检测大鼠空腹血糖、总胆固醇（ TC）、三酰甘油（ TG）、高密度脂蛋白胆固醇（ HDL-C）和低密度脂蛋白胆固醇（ LDL-C）水平;行Y迷宫实验,记录并比较1组大鼠学习和记忆能力测试中达到＂学会标准＂所需电击次数;行Morris水迷宫实验,记录并比较1组大鼠的逃避潜伏期。迷宫实验结束后观察1组大鼠海马CA1区组织形态学变化。结果奥氮平组大鼠灌胃第1、3、4周体重均高于同期正常对照组（均 P﹤0.05）,第4周时体重超过正常对照组平均体重的10%（P﹤0.05）。灌胃4周后,奥氮平组大鼠空腹血糖和血清TG、TC、LDL-C水平明显高于对照组,HDL-C明显低于正常对照组,差异均有统计学意义（均P﹤0.05）。Y迷宫实验显示奥氮平组大鼠所需电击次数明显多于正常对照组[（81.65±0.11）次比（50.15±0.01）次,P﹤0.05];Morris水迷宫实验显示奥氮平组大鼠逃避潜伏期明显长于正常对照组[（61.10±0.10）s比（13.54±0.11）s,P﹤0.05]。灌胃4周后奥氮平组大脑海马CA1区神经细胞出现排列不齐、缺失和水肿等变化。结论奥氮平可致大鼠血糖和血脂水平升高并影响认知功能。     

七氟醚麻醉对子代大鼠海马神经元自噬的影响

目的探讨七氟醚麻醉对子代大鼠海马神经元自噬的影响。方法孕5~7 d的SD雌鼠18只,采用随机数字表法将其分为3组(n=6):对照组(C组)、七氟醚组(S组)、七氟醚+自噬抑制剂wortmannin组(SW组)。C组母鼠仅置于麻醉箱内,通入相同流量氧气暴露4 h,S组和SW组母鼠给予2.8%七氟醚吸入麻醉4 h。SW组子代大鼠于出生后1~3 d腹腔注射0.5 mg/kg自噬抑制剂wortmannin,C组和S组于相同时点腹腔注射等量的生理盐水对照。于出生后22 d,对各组子代大鼠进行水迷宫实验,测定其学习记忆功能,出生后28 d,完成水迷宫测试后处死子代大鼠,并取其海马组织。采用TUNEL染色测定子代大鼠海马组织内神经元的凋亡率,采用Western blot法检测子代大鼠海马组织内微管相关蛋白l轻链3(LC3)Ⅱ/LC3Ⅰ比值作为自噬活性的指标。结果 S组、C组子代大鼠逃避潜伏期较C组,穿越平台次数比较差异无统计学意义(P>0.05),SW组子代大鼠逃避潜伏期较C组延长,穿越平台次数较C组减少(P<0.05)。与C组比较,S组和SW组子代大鼠海马神经元的凋亡率和LC3Ⅱ/LC3Ⅰ比值均升高(P<0.05);与S组比较,SW组子代大鼠海马神经元的LC3Ⅱ/LC3Ⅰ比值降低(P<0.05)。结论大鼠孕期七氟醚麻醉对子代学习记忆功能无影响,其机制与激活生理性自噬对抗神经元凋亡有关。