胰岛淀粉样多肽、葡萄糖转运蛋白2在海洛因戒断、脱毒和复吸大鼠胰岛β细胞中的表达

目的探讨在大鼠海洛因戒断、脱毒治疗和复吸期间,胰岛淀粉样多肽(IAPP)和葡萄糖转运蛋白2(GLUT2)在胰岛β细胞内表达的变化。方法正常雄性SD大鼠32只,随机分为实验组(n=24)和正常对照组(n=8),实验组又分为海洛因依赖戒断组、美沙酮脱毒治疗组和海洛因复吸组。各组大鼠取胰腺组织,采用免疫组织化学SABC法及图像分析方法进行研究。结果海洛因戒断时IAPP和GLUT2阳性细胞免疫染色较正常对照组变深,平均灰度值均低于正常组(P0.05),IAPP面数密度增大(P0.05);美沙酮脱毒期间,IAPP和GLUT2免疫阳性细胞染色变浅,平均灰度值较戒断时升高,与正常组差异无统计学意义,IAPP面数密度于正常组比较差异不显著(P0.05);海洛因复吸期间,IAPP和GLUT2阳性细胞免疫染色又加深,平均灰度值降低(P0.05),IAPP面数密度再次增大(P0.05)。结论在海洛因戒断和复吸期间,表达于大鼠胰岛β细胞的IAPP和GLUT2合成增加,美沙酮脱毒期间合成减少,两者变化规律一致,提示在海洛因戒断,脱毒和复吸过程中,两者的合成同步,可能参与调节海洛因戒断,美沙酮脱毒治疗及复吸大鼠机体能量代谢过程,与调节大鼠摄食、体重及保护胰岛细胞功能有关。     

亮氨酸脑啡肽、胆囊收缩素在海洛因戒断、复吸大鼠脑VTA、NAc区神经元的表达

目的:观察海洛因戒断、复吸大鼠脑VTA、NAc内亮氨酸脑啡肽(leucine-enkephalin,Leu-Enk)和胆囊收缩素(cholecystokinin,CCK)的变化,探讨CCK和内源性阿片肽在海洛因戒断、脱毒和复吸过程中的作用及其相互关系。方法:正常雄性SD大鼠63只,随机分为实验组、盐水对照组和正常对照组。实验组大鼠又分海洛因戒断组、美沙酮脱毒组和海洛因复吸组。取实验各组及对照组大鼠脑组织,定位VTA和NAc,用免疫组化SABC法显示VTA,NAc区Leu-Enk,CCK阳性细胞并用图像分析法测定平均光密度值。结果:(1)Leu-Enk在实验各组大鼠VTA和NAc内的表达与对照组比较均显著降低(P<0.05)。(2)与对照组比较,海洛因戒断、复吸组大鼠VTA和NAc中CCK阳性细胞免疫反应增强,差异有显著性(P<0.05);经美沙酮脱毒后恢复正常。结论:海洛因戒断造成的机体应激及阿片类药物均抑制了VTA和NAc中Leu-Enk的分泌;CCK分泌增加,参与了对脑神经的保护。     

BDNF和GDNF在海洛因诱导条件性位置偏爱大鼠mPFC的表达

目的:研究大鼠边缘前区(PrL)和下边缘皮层(IL)BDNF和GDNF在海洛因诱导条件性位置偏爱(CPP)及戒断状态的表达变化.方法:SD大鼠随机分为对照组(control)和海洛因诱导组,海洛因诱导组分为海洛因诱导CPP状态(heroin)和戒断状态(withdrawal).小剂量递增法行海洛因诱导CPP建模,并自然...     

TH和DβH在海洛因戒断、复吸大鼠脑VTA、NAc区神经元的表达

目的　观察海洛因戒断、复吸对大鼠脑VTA、NAc神经元表达酪氨酸羟化酶（TH）和多巴胺β羟化酶（DβH）的影响,探讨多巴胺（DA）和去甲肾上腺素（NE）在海洛因戒断、复吸过程中的调节机制及相互关系。 方法　将正常雄性SD大鼠63只,随机分为实验组21只、盐水对照组21只和正常对照组　21只,实验组大鼠又分海洛因戒断组、美沙酮脱毒组和海洛因复吸组。取正常对照组、盐水对照组及实验各组大鼠的脑组织,用免疫组化SABC法显示VTA、NAc区TH、DβH阳性神经元并用图像分析法测定平均光密度值。 结果　与正常及盐水对照组比较：（1）海洛因戒断组和复吸组大鼠VTA、NAc内TH表达均增强,经美沙酮脱毒之后恢复正常;（2）DβH的表达在戒断组大鼠VTA、NAc内有所增强,但在脱毒组和复吸组均减弱。 结论　在海洛因戒断、脱毒和复吸期间,VTA、NAc区神经元的DA和NE相互调节,是产生奖赏效应的重要神经递质。     

电针对海洛因成瘾大鼠PAG内细胞凋亡和caspase-3表达的影响

目的:研究电针对海洛因成瘾大鼠中脑导水管周围灰质(periaqueductal gray,PAG)的细胞凋亡及caspase-3表达的影响。方法:大鼠被随机分为四组:正常对照组、海洛因成瘾组(成瘾组)、海洛因戒断组(戒断组)和海洛因戒断针刺组(针刺组)。按给药剂量逐日递增的原则皮下注射海洛因建立成瘾模型;针刺组大鼠成瘾后用韩氏穴位神经刺激器(HNAS)针刺双侧"足三里"和"三阴交"穴位,30min,每日1次,连续5d;免疫组织化学染色法测caspase-3的表达;流式细胞仪测细胞凋亡情况。结果:(1)与正常组相比,成瘾组、戒断组和针刺组大鼠PAG内的细胞凋亡和caspase-3的表达均增多(P0.05);(2)针刺组与成瘾组和戒断组相比,针刺组PAG内的细胞凋亡和caspase-3的表达均减少(P0.05)。结论:(1)海洛因成瘾导致大鼠PAG内细胞凋亡和caspase-3的表达增多;(2)HANS针刺对海洛因成瘾引起的大鼠细胞凋亡有抑制作用,并下调大鼠PAG内caspase-3的表达。     

吗啡慢性处理及戒断后不同时期大鼠海马脑源性神经营养因子与trkB表达的变化

目的:观察吗啡慢性处理及戒断后不同时期大鼠海马内脑源性神经营养因子(BDNF)与trkB的表达.方法: 实验组雄性成年SD大鼠以剂量递增的方法连续腹腔注射吗啡10d,每天2次.动物在戒断后0、1、7、14d和21d处死.对照组动物注射等量生理盐水,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与trkB的表达.用Motic 3.2图像分析系统测定免疫阳性产物的平均光密度值.结果: 实验组BDNF免疫阳性产物的平均光密度值在戒断后0、1、7、14d和21d分别低于相应对照组,差异具有统计学意义,以戒断后14d下降最为明显.实验组trkB免疫阳性产物的平均光密度值在戒断后0、1、7、14d和21d分别也低于相应对照组,差异具有统计学意义.结论: 大鼠慢性吗啡成瘾及戒断后不同时间点BDNF与trkB在海马CA1区的表达明显下降,这种下降可能与大鼠吗啡成瘾及戒断后不同时期的行为学变化有关.     

八肽胆囊收缩素在吗啡依赖及戒断大鼠相关脑区的表达变化

目的:探究慢性吗啡依赖及戒断大鼠相关脑区八肽胆囊收缩素(CCK-8)表达的变化。方法:利用Wistar大鼠建立慢性吗啡依赖及戒断模型,分为对照组(control)、吗啡依赖组(MOR)、纳洛酮催促戒断组(NAL)。Gellert-Holtzman评分评价吗啡成瘾及戒断程度,采用免疫组织化学和原位杂交技术分别检测相关脑区CCK-8蛋白及CCK mRNA表达的变化。结果:戒断组Gellert-Holtzman评分与对照组和吗啡依赖组比较显著增加;前额叶皮质(PFC)、黑质致密部(SNc)、中脑腹侧被盖区(VTA)CCK-8及CCK mRNA表达依赖组较对组明显升高,戒断后表达下降;杏仁核、蓝斑(LC)吗啡依赖后CCK-8及CCK mRNA表达较对照组显著增高,海马齿状回(PoDG)、杏仁核、LC戒断后较依赖组表达进一步升高;尾壳核(CPU)、伏隔核(NAc)、中脑导水管周围灰质(PAG)未检测到CCK-8及CCK mRNA的表达。结论:CCK-8参与了大鼠吗啡依赖与戒断过程并具有脑区特异性。     

海洛因戒断、复吸对大鼠十二指肠5-羟色胺、胃泌素、生长抑素免疫反应细胞表达的影响

目的 研究海洛因戒断、复吸期间5-羟色胺（5-HT）、胃泌素(Gas)、生长抑素（SS）在大鼠十二指肠表达的变化,探讨十二指肠5-HT、Gas、SS在海洛因戒断和复吸期间的可能作用。 方法 正常雄性SD大鼠35只,随机分为实验组15只、生理盐水对照组15只和正常对照组5只,实验组大鼠又分戒断组（HAG）、脱毒治疗组（MDG）、复吸组(HRG)。取正常对照组、生理盐水对照组及实验各组大鼠的十二指肠组织,采用免疫组织化学SABC法、细胞计数及图像分析方法进行研究。 结果 与正常对照组及生理盐水对照组比较,戒断及复吸组大鼠十二指肠内的5-HT、Gas、SS免疫反应细胞数量均增加（P<0.05）,图像分析测得5-HT、Gas、SS免疫反应细胞的平均灰度值均低于正常及生理盐水对照组（P<0.05）。脱毒治疗组与正常及生理盐水对照组比较,3种免疫反应细胞的计数及图像分析变化差异均无统计学意义（P﹥0.05）。 结论 在海洛因戒断、复吸期间,5-HT、Gas、SS在十二指肠表达增强,3种免疫反应细胞合成和分泌5-HT、Gas、SS增多,提示机体十二指肠内3种生物活性物质均参与机体对海洛因损伤的调节;用美沙酮脱毒治疗后5-HT、Gas、SS的表达接近正常,提示经美沙酮治疗,海洛因依赖大鼠十二指肠的5-HT、Gas、SS含量变化是可逆的。     

海洛因成瘾大鼠模型的方法建立

目的模仿人类吸毒成瘾的大量临床实例,建立海洛因成瘾大白鼠模型。方法采用递增法人为地给大白鼠皮下注射海洛因造成动物成瘾,动物设对照组和模型组。用纳洛酮促戒断,戒断症状按Maldonado评分法给予评分。结果模型组海洛因成瘾大鼠出现明显的依赖戒断症状,戒断评分值明显高于空白对照组(P<0.01)。结论用递增法皮下注射海洛因建立的海洛因成瘾大鼠模型,可在28天内形成海洛因依赖模型,该模型稳定可靠。     

神经营养因子受体同源物2通过上调proNGF、sortilin、p75NTR表达诱导脑出血后血肿周围脑组织细胞凋亡

目的探讨脑出血后不同时期血肿周围脑组织中神经营养因子受体同源物2(NRH2)、神经生长因子前体(pro NGF)、sortilin、神经营养因子受体p75(p75NTR)表达及与细胞凋亡的关系。方法收集临床脑出血后实施血肿清除术的周围组织标本,根据脑出血距离标本取出时间,分为6h以内(包括6h)、6h以上至24h(包括24h)、24h以上至72h(包括72h)、72h以上4组,同时取10例手术过程中血肿远隔部位掉落的组织块作为对照组,通过末端脱氧核糖核酸转移酶介导的脱氧尿苷三磷酸缺口末端标记法(TUNEL)测定脑细胞的凋亡指数(AI),采用实时荧光定量PCR、Western blot法分别检测脑组织中NRH2、pro NGF、sortilin、p75NTR mRNA和蛋白表达,Western blot法检测脑组织中Bcl-2、Bax的表达。体外培养大鼠皮层星形胶质细胞,经NRH2 siRNA或scramble siRNA转染后,Western blot法检测pro NGF、sortilin、p75NTR蛋白表达。结果与对照组以及6h以内的脑出血组相比,脑出血后6h以上各组AI升高,以24h以上至72h内组为最高,但6h以内的脑出血组AI与对照组无区别。随着脑出血时间的延长,pro NGF、p75NTR mRNA和蛋白表达水平逐渐升高,24h以上至72h达到高峰,72h后仍处于较高水平。与对照组和6h以内的脑出血组比较,脑出血后6h以上至24h内(包括24h),脑组织NRH2、sortilin的mRNA与蛋白表达水平及Bax表达水平即增加,24h以上至72h内达高峰,72h后仍维持在较高水平。但与对照组比较,6h以内的脑出血组上述指标无显著性差异。与对照组相比,6h以内的脑出血组Bcl-2表达水平无明显变化,脑出血后6h以上的脑出血各组脑组织Bcl-2表达水平降低,以24h以上至72h内处于最低值。NRH2 siRNA组pro NGF、sortilin、p75NTR蛋白表达水平明显低于空白对照组、scramble siRNA组。结论 NRH2在脑出血后血肿周围脑组织中表达增加,通过促进pro NGF、sortilin、p75NTR表达增加Bax/Bcl-2比率,从而诱导脑细胞凋亡。     

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...