吗啡成瘾戒断对大鼠海马CA1区P-CREB表达的影响

目的探讨吗啡成瘾戒断后大鼠海马CA1区P-CREB的表达变化。方法48只健康雄性成年SD大鼠,随机分为实验组和对照组:实验组腹腔注射吗啡起始剂量5mg/kg,1d2次,逐日递增,连续10d;对照组:以生理盐水代替吗啡。停药后7d、14d和21d处死。用免疫组织化学方法(ABC法)检测海马CA1区P-CREB的表达,图像分析系统测定阳性反应产物的平均灰度值。结果P-CREB表达在7d、14d实验组与对照组相比表达上调(P<0.05),21d与对照组比较无显著差异(P>0.05)。结论海马CA1区CREB磷酸化在吗啡依赖的形成中发挥作用。     

大鼠空间辨别性学习记忆活动对海马结构Ephrin-A3表达的影响

为了探讨大鼠获得空间辨别性学习记忆活动对导向分子ephrin-A3表达的影响,本研究采用免疫组织化学染色和Western blot方法对模型组、游水组和对照组大鼠海马内ephrin-A3的表达部位和表达量进行对比研究。免疫组织化学染色结果显示模型组、游水组和对照组海马结构内各亚区和各层内均可见ephrin-A3样免疫阳性产物分布,模型组大鼠海马CA3区辐射层和腔隙层尤为明显;Western blot方法检测模型组大鼠海马结构内ephrin-A3阳性产物平均积分光密度值明显高于游水组和对照组。模型组内训练14d的大鼠海马结构内ephrin-A3阳性产物平均积分光密度值高于训练7d和21d。以上研究结果提示eph-rin-A3的表达与大鼠空间辨别性学习记忆活动有密切关系。     

酒精处理影响青春期大鼠海马CA1区BDNF和TrkB的表达

为探讨青春期饮酒致学习记忆力下降的可能机制,本研究观察了青春期大鼠酒精处理后海马CA1区脑源性神经营养因子(BDNF)和酪氨酸激酶受体B(TrkB)的表达变化。实验选用30d龄SD雄性大鼠,以25%的酒精按8g/kg/d灌胃,连续灌7d,动物分别在停酒后0d,3d,7d和14d处死;对照组以等量生理盐水代替酒精按同样方法处理。用免疫组织化学方法(ABC法)检测海马CA1区BDNF和TrkB的表达,Motic3.2图像分析系统测定免疫阳性产物的平均灰度值。结果显示,BDNF的表达在停酒后0d和14d,实验组与相应对照组相比差异无显著性(P>0.05);3d显著升高(P<0.05);7d明显下降(P<0.05)。TrkB的表达在停酒后0d,3d,7d,实验组与相应对照组相比差异无显著性(P>0.05);14d显著下降(P<0.05)。以上结果提示,BDNF表达的相对不足可能是青春期饮酒致学习记忆力持续性下降的原因之一。     

Caspase-9在生后小鼠海马发育中的表达

目的观察小鼠海马发育过程中凋亡相关基因caspase-9的表达变化。方法取出生后1d、3d、7d、14d、21d和28d的小鼠海马,应用免疫组织化学技术、免疫印迹技术及图像分析技术检测caspase-9的表达变化。结果 P1 d海马CA区锥体细胞层和齿状回颗粒细胞层caspase-9阳性表达产物平均光密度最高,P3 d~P21 d caspase-9阳性表达产物平均光密度逐渐降低,P28表达水平最低。结论凋亡相关基因caspase-9在生后小鼠海马发育过程表达水平呈逐渐降低的趋势。     

慢性吗啡处理及戒断后大鼠前额皮质、海马和杏仁核中Parvalbumin的表达变化

为了观察慢性吗啡处理及戒断后大鼠前额皮质、海马和杏仁核中parvalbumin(PV)的表达变化,为其功能的研究提供形态学依据,本实验将30只雄性SD大鼠随机分为吗啡依赖组和生理盐水对照组。吗啡依赖组大鼠腹膜腔注射吗啡,2次/d,起始剂量为5mg/kg,逐日递增5mg,至第10d为50mg/kg;对照组注射同体积的生理盐水。于末次注射后动物分别存活3h、3d和14d。用免疫组化方法和相对平均灰度值检测前额皮质、海马和杏仁核内PV的表达。结果显示:在生理盐水处理组各存活时间点,前额皮质、海马和杏仁核内PV的表达相同。和生理盐水对照组相比,3h时海马和杏仁核内PV的表达明显增加(P<0.05),但前额皮质内PV的表达减少。第3d时,海马CA1、CA3、CA4、齿状回和杏仁核内PV的表达减少,但CA2区PV表达继续增加,而前额皮质的表达开始恢复。至第14d时,CA2区PV的表达开始恢复,但CA1、CA4和杏仁核内PV的表达又开始增加,明显高于第3d组(P<0.05)。以上结果提示慢性吗啡处理及戒断后PV的表达具有区域特异性和时相特异性;这种变化在戒断早期可能主要与躯体依赖相关,而戒断晚期主要与精神依赖相关。     

慢性脑缺血大鼠海马CA_1区中的BDNF表达

为了观察慢性脑缺血时海马CA1区中BDNF的表达变化,探讨缺血性脑损伤及修复机制。我们将Wistar大鼠双侧颈总动脉结扎制成慢性脑缺血动物模型。分为三组:正常对照组、慢性脑缺血30d和120d组。分别于术后30d和120d处死动物,行BDNF免疫组化染色,计数各组大鼠海马CA1区中的阳性神经元数。结果显示:(1)在对照组的海马CA1区可见BDNF较强的表达;(2)在慢性脑缺血30d时,海马CA1区BDNF的表达高于缺血120d组及对照组(P<0.05)。而120d时,海马CA1区BDNF的表达与对照组无显著性差异(P>0.05)。结果提示:(1)在正常大鼠海马CA1区有BDNF表达,能维持神经元的存活;(2)慢性脑缺血时,BDNF在海马CA1区的表达先升后降。     

吗啡依赖小鼠海马神经元c-fos的表达

目的:探讨吗啡依赖小鼠海马不同亚区神经元c-fos表达的差异。方法:以剂量递增法皮下注射吗啡建立吗啡依赖小鼠模型,腹腔注射纳洛酮诱发戒断症状。根据小鼠戒断反应中出现的跳跃次数、体重下降等指标评定戒断反应强度。采用免疫组织化学法显示吗啡依赖小鼠和正常对照组小鼠海马神经元c-fos的表达。结果:吗啡依赖组海马CA1区和齿状回Fos阳性神经元数目明显增加(P<0.05),CA3区无明显改变(P>0.05)。纳洛酮催促戒断组海马CA1和CA3区Fos阳性神经元数目明显增加(P<0.05),齿状回Fos阳性神经元数目增加更为明显(P<0.01)。吗啡依赖组与纳洛酮催促戒断组CA3区阳性神经元数目有显著性差异(P<0.05)。结论:海马神经元c-fos的表达增强可能与吗啡依赖对神经元的损伤有关。     

BDNF对体外培养的大鼠脊髓前角神经元内突触素Ⅰ与突触囊泡素表达的影响

探讨BDNF对体外培养的大鼠脊髓前角神经元内突触素I与突触囊泡素(SYN)表达的影响。取孕14d大鼠子宫内胎鼠的脊髓腹侧部分神经元,体外有血清培养。在培养7d后,随机分成对照组、BDNF组和抗BDNF组。BDNF组培养液中加入BDNF(20ng/ml),抗BDNF组培养液中加入BDNF抗体(20μg/ml),对照组加入等量Hanks液。3d后在倒置显微镜下计数三组神经元存活数,并用NF200、MAP2、NSE的免疫组化反应对神经细胞进行鉴定。行突触素I与SYN免疫组化反应,对部分细胞行突触素ImRNA原位杂交反应,运用图像分析系统对突触素I与SYN免疫组织反应阳性产物以及突触素I原位杂交反应阳性产物作光密度分析。结果发现有血清培养时各组脊髓前角神经元的存活数无显著差异(P>0.05);BDNF组突触素I与SYN免疫反应阳性产物的平均光密度值高于其它两组,抗BDNF组最低(P<0.01)。BDNF组突触素ImRNA阳性产物的平均光密度值明显高于其它两组,抗BDNF组突触素ImRNA阳性产物的平均光密度值最低(P<0.01)。本研究结果提示BDNF对有血清培养时脊髓前角神经元的存活没有明显影响,但BDNF可明显上调培养的脊髓前角神经元内突触素I与SYN的表达。     

金雀异黄酮对去卵巢大鼠海马突触体素表达的影响

目的：研究金雀异黄酮对去卵巢大鼠海马突触体素的影响,以探讨金雀异黄酮对女性更年期后中枢神经系统退行性变的作用机制。方法：用免疫组化结合图像分析的方法,测量分析去卵巢后不同时间点以及给予金雀异黄酮替代治疗后海马CA1～3区辐射层和齿状回分子层突触体素免疫阳性产物的平均光密度变化。结果：去卵巢后大鼠CA1～3区辐射层和DG分子层突触体素免疫阳性产物的平均光密度值逐渐降低,4周后与假手术组和苯甲酸雌二醇组相比有显著差异;金雀异黄酮组治疗后海马突触体素免疫阳性产物平均光密度恢复。结论：金雀异黄酮能恢复去卵巢大鼠海马突触密度,延缓女性更年期后中枢神经系统的退行性变。     

人参皂甙Rb1对血管性痴呆大鼠认知功能及突触素表达的影响

目的:研究人参皂甙Rb1 (GSRb1)对血管性痴呆大鼠认知功能与海马突触素表达的影响.方法:将36只大鼠随机分为对照组、模型组和治疗组.以双侧颈总动脉结扎法制作血管性痴呆大鼠模型.造模后治疗组大鼠腹腔注射GSRb1(30mg·kg-1·d-1).Y型迷宫和免疫组织化学法结合图像分析检测各组大鼠认知功能和海马突触素免疫阳性产物的平均光密度.结果:与对照组大鼠相比,模型组大鼠Y型迷宫中错误次数增加,模型组大鼠学习记忆能力减退,其海马区突触素免疫反应阳性产物平均光密度降低;与模型组相比,治疗组大鼠出错次数减少,而海马区突触素免疫阳性产物平均光密度升高.结论:人参皂甙Rb1可增加血管痴呆性大鼠海马区突触素表达,显著改善其认知功能.     

Modes of reinforcement and gender and culture of experimenter and subject: effects of "alien" and external reinforcement for Japanese and American men and women

In this study, we examined external and "alien" reinforcement (ER and AR. respectively) as a factor in social learning, and studied the combined effects of culture and reinforcement mode. A female (Experiment 1) and a male (Experiment 2) experimenters conducted experimental sessions. Both men and women, who grew up in the same culture as the experimenter, participated and performed the experimental task. A three-way interaction effect of experimenter gender, culture, and reinforcement mode was found on task performance. And the effect was more pronounced for a Japanese experimenter. A female and a male experimenters conducted Experiments 3 and 4, respectively; however participants this time were men and women who grew up in different cultures than the experimenter. Results indicated that the pattern of the subject gender and reinforcement mode interaction effect, when the experimenter was Japanese with American subjects, was exactly opposite to that when the experimenter was American. These experiments showed that AR was as effective for social learning as ER, and that the cultural backgrounds of experimenter and subject influenced AR and ER effectiveness.     

Rates of oxygen consumption and of anaerobic glycolysis in renal cortex and medulla of adult and new-born rats and guinea-pigs

1. Rates of oxygen uptake and of anaerobic glycolysis were estimated in slices from the renal cortex and medulla (a) of adult rats and guinea-pigs, (b) of new-born (1-, 5- and 21-day-old) rats and of guinea-pigs of 1, 12, 21, 24 and 120 hr age.2. In the adult rat, Q(O2) values for the cortex were 12.55 +/- 0.20 (22) and for the medulla: 8.56 +/- 0.17 (22) mul./hr.mg dry weight, while in the new-born rat (24 hr old) they were 10.99 +/- 0.46 (12) and 9.33 +/- 0.18 (9) mul./hr.mg dry weight respectively.3. Values for Q(CO2) (N2) (anaerobic glycolysis) in the 14 hr old new-born rat were in the renal cortex 9.65 +/- 0.35 (5) and in the medulla 7.39 +/- 0.43 (5) mul./hr.mg dry weight; while in the adult they were 2.25 +/- 0.08 (16) and 5.76 +/- 0.14 (16) mul./hr.mg dry weight, respectively.4. In the adult guinea-pig values for Q(CO2) (N2) were of the same order as in the adult rat, though the rate of O(2) uptake was for the cortex 8.12 +/- 0.22 (12) and for the medulla 5.02 +/- 0.23 (11) mul./hr.mg dry weight.5. Though the Q(O2) values in the renal cortex and medulla were smaller in the 1 hr old new-born guinea-pig, they were already increasing in the 12 hr old neonate.6. The results are discussed in the light of enzyme changes occurring during the process of maturation of the nephron as indicated by histochemical observations.     

Timing and intensity of early fevers and the development of allergies and asthma

BACKGROUND: Early childhood fevers appear to protect against later allergies and asthma. What is not known is the time in which fevers exert this effect and whether the degree of temperature increase is important. OBJECTIVE: We sought to examine the relationship between the time and degree of early fevers and later allergies and asthma. METHODS: Eight hundred thirty-five children from southeast Michigan were enrolled at birth. Clinic records from their first 2 years were abstracted for episodes of fever. At age 6 to 7 years, children underwent allergy testing. We examined fevers occurring within 6-month intervals in the first 2 years of life and outcomes at age 6 to 7 years. The primary outcome measures were allergic sensitization, asthma, asthma with allergic sensitization, and asthma without allergic sensitization. RESULTS: In the unadjusted analysis each episode of fever between 7 and 12 months of age was associated with a lower odds of allergic sensitization (odds ratio [OR], 0.71; 95% CI, 0.54-0.93) and asthma with allergic sensitization (OR, 0.43; 95% CI, 0.21-0.90) at age 6 to 7 years. Likewise, every 1 degrees C increase in the maximum temperature between 7 and 12 months was associated with a lower odds of allergic sensitization (OR, 0.77; 95% CI, 0.61-0.96) and asthma with allergic sensitization (OR, 0.62; 95% CI, 0.40-0.94). After adjusting for potential confounders, each episode of fever between 7 and 12 months was associated with a lower likelihood of asthma with allergic sensitization (adjusted OR, 0.33; 95% CI, 0.11-0.94) at age 6 to 7 years. CONCLUSIONS: Both the timing and intensity of childhood fevers appear to be important factors in the development of allergies and asthma.     

纳米水平分子成像与诊疗一体化研究进展与挑战

分子成像能以非侵入性的方式重现活体细胞的生理功能和生物学过程,提高疾病的早期和特异性诊断水平。纳米颗粒/材料具有物理性质可控性高、易于表面修饰、血液循环时间长和可功能化等优点,在疾病诊断与治疗中显示出巨大潜力。但如何阐明纳米材料多功能间的内在联系、解决其代谢及安全性等关键机制难题、实现纳米颗粒/材料多功能性到临床多功能...