lactuside B降低脑缺血损伤大鼠海马和纹状体TRPM7 mRNA的表达

目的探讨lactuside B对大鼠脑缺血损伤后海马和纹状体TRPM7 mRNA表达的影响。方法采用大脑中动脉缺血再灌注损伤模型,SD雄性大鼠缺血2 h后再灌,分别于再灌后ip给予lactuside B 12.5,25和50 mg·kg-1,每天2次,每组1/2大鼠给药1 d,另1/2大鼠连续给药3 d,于末次给药后观察神经缺失症状并处死大鼠;RT-PCR技术检测大脑皮质和海马TRPM7 mRNA的表达。结果模型组大鼠各时间段神经缺失症状评分明显升高,海马和纹状体的TRPM7 mRNA表达均显著增加(P<0.01)。给予lactuside B12.5,25和50 mg·kg-11 d后,海马和纹状体TRPM7 mRNA表达分别为0.68±0.02,0.55±0.02和0.56±0.02,及0.32±0.02,0.25±0.01和0.35±0.01,与模型对照组比较均明显降低(P<0.01);给予lactuside B 12.5,25和50 mg·kg-1 3 d,海马和纹状体TRPM7 mRNA分别为0.29±0.02,0.18±0.01和0.26±0.01,及0.28±0.02,0.19±0.01和0.27±0.01,与模型对照组比较均明显降低(P<0.01)。结论lactuside B可降低海马和纹状体TRPM7基因的表达,提示该化合物对脑缺血损伤可能具有治疗作用。     

人脐带间质干细胞对大鼠的免疫毒性研究

目的:研究人脐带间质干细胞(UCMSC)对Wistar大鼠的免疫毒性作用。方法:SPF级Wistar大鼠112只分为4组:溶媒组(给予溶媒5 ml/kg)、低剂量组(给予人UCMSC 1×107个/kg)、高剂量组(给予人UCMSC 5×107个/kg)和对照组(给予大鼠UCMSC 1×107个/kg)。每组28只大鼠,雌雄各14只。大鼠尾静脉注射给药,2周1次,共注射4次。给UCMSC后每周进行受体鼠临床移植物抗宿主病(GVHD)评分,末次注射UCMSC后1、13周检测血IgG、IgM含量,CD3+、CD4+、CD8+T细胞数量,并对大鼠淋巴结、胸腺、脾脏进行脏器系数计算和组织病理学检查。结果:给予UCMSC后,各组大鼠的GVHD评分值均为0。末次给予UCMSC后1周,低、高剂量组雌性大鼠IgG[(0.65±0.12)、(0.63±0.14)g/L]和IgM含量[(0.06±0.01)、(0.06±0.01)g/L]明显高于溶媒组雄性大鼠[(0.41±0.17)g/L、(0.04±0.01)g/L,P<0.01或P<0.05];高剂量组雄性大鼠IgM含量[(0.05±0.01)g/L]明显高于溶媒组雄性大鼠[(0.03±0.01)g/L,P<0.01];对照组雌性、雄性大鼠IgM[(0.06±0.02)、(0.05±0.02)g/L]也明显高于溶媒组(P<0.01或P<0.05)。末次给予UCMSC后13周,各剂量组雌、雄性大鼠IgG、IgM与溶媒组相比差异均无统计学意义(均P>0.05)。末次给予UCMSC后1周,低、高剂量组雌性大鼠的脾脏系数[分别为(0.274±0.016)%、(0.294±0.019)%]明显高于溶媒组[(0.232±0.012)%,P<0.01];高剂量组雄性大鼠的脾脏系数[(0.242±0.027)%]明显高于溶媒组[(0.202±0.012)%,P<0.01];对照组雌、雄性大鼠脾脏系数[分别为(0.261±0.019)%、(0.236±0.014)%]也明显高于溶媒组(P<0.05或P<0.01)。末次给予UCMSC后13周各组大鼠的脾脏和胸腺系数差异均无统计学意义(均P>0.05)。各组大鼠CD3+、CD4+、CD8+T细胞百分比及CD4+/CD8+比值均在正常范围内。各组大鼠胸腺、脾脏和肠系膜淋巴结组织病理学检查均未见明显异常。结论:人脐带间质干细胞可引起正常Wistar大鼠免疫球蛋白含量和脾脏系数的升高,该作用具有一过性和可逆性。     

四味甘温归肝肾经中药对性激素致大鼠肾阳虚的影响

目的观察杜仲、何首乌、海马、菟丝子四味归肝肾经中药对性激素致大鼠肾阳虚的影响,认识"甘,温,归肝、肾经"中药药性的现代科学内涵。方法采用腹腔注射苯甲酸雌二醇造成雄性大鼠肾阳虚模型、腹腔注射丙酸睾酮造成雌性大鼠肾阳虚模型。SD大鼠70只,随机分为7组:正常对照组、模型对照组、金匮肾气丸组、杜仲组、何首乌组、海马组、菟丝子组,每组10只,灌胃给药,每日1次,连续12 d。测定大鼠抓力、肛温、睾丸指数、附睾指数、前列腺指数、精囊腺指数、卵巢指数、子宫指数。结果①杜仲、海马、菟丝子三味中药均可提高肾阳虚大鼠抓力,因其均入肝肾经从而改善腰膝酸软。②杜仲、海马、菟丝子三味中药可升高肾阳虚大鼠的肛温,因其性温从而起温煦作用。③杜仲、何首乌可升高雄性肾阳虚大鼠的睾丸指数,海马可提高雄性肾阳虚大鼠精囊腺指数,菟丝子可恢复雄性肾阳虚大鼠前列腺指数,何首乌、菟丝子可改善雌性肾阳虚大鼠的卵巢指数,四味中药能不同程度改善肾阳虚证之性欲减退、肾精亏虚等症状与其入肾经有关。结论杜仲、海马、菟丝子、何首乌四味中药能不同程度改善肾阳虚证之腰膝酸软、畏寒肢冷、性欲减退、肾精亏虚等症状相关作用,这为探讨"甘温归肝肾经"中药的共同作用规律提供了新内容。     

新生小鼠小脑提取液对成年小鼠神经干细胞分裂与增殖的影响

目的:探讨新生小鼠小脑提取液(ECNM)对成年小鼠脑内神经干细胞分裂与增殖的影响.方法:采用脑立体定位给药技术,将ECNM注入前脑和海马,应用Nestin单抗做免疫组化染色,显示神经干细胞.结果:给予ECNM后7d和14d,在前脑和海马均可见密集的神经干细胞,对照组未见阳性染色.结论:ECNM可诱导成年小鼠神经干细胞分裂与增殖.     

胸腺和性激素对大鼠肝脏脂质过氧化的调节作用(英文)

本文应用成年去胸腺或去性腺Wistar大鼠研究了胸腺对肝脏脂质过氧化(LPO)的影响及其与性激素有关的中间途径,结果表明,雌性成年去胸腺(ATx)大鼠肝匀浆丙二醛(MDA)含量增高,但雄性ATx大鼠肝脏MDA无明显变化;同时雌性ATx大鼠血浆雌二醇水平下降,雄性ATx大鼠血浆睾酮浓度降低,雌性大鼠卵巢切除术后肝脏MDA的变化与胸腺切除术后的变化相似,给予雌二醇可逆转去卵巢大鼠肝脏MDA的增高,在雄性大鼠中,无论是切除睾丸还是睾丸切除后补充睾酮对肝脏MDA均无明显影响,此外,给雌性ATx大鼠注射雌二醇可逆转其肝脏MDA的增高,这些结果提示胸腺在调节雌性大鼠肝脏抗氧化功能中起着重要作用,这种作用可能通过雌激素介导,因此我们设想在体内可能存在:胸腺-雌激素-肝脏通路”,它参与对肝脏抗氧化功能的调节。     

3,4-亚甲基二氧基甲基苯丙胺对大鼠的神经毒性及维生素C的保护作用

目的:探讨3,4-亚甲基二氧基甲基苯丙胺(MDMA)的神经毒性机制及抗氧化剂维生素C是否具有MDMA神经毒性的保护作用.方法:雄性Wistar大鼠随机分为正常对照组、MDMA组、MDMA给药前30 min给予维生素C组、MDMA给药后3 h给予维生素C组、MDMA给药后5 h给予维生素C组,MDMA和维生素C均为单剂量腹腔注射,剂量分别为20和250 mg·kg-1.1周后采用高效液相色谱法测定海马、枕叶皮层5-羟色胺(5-HT)的含量,原位杂交方法检测SERTmRNA,免疫组织化学法检测GFAP蛋白.结果:与正常对照组比较,MDMA组大鼠枕叶皮层、海马5-HT含量均明显下降(P<0.05),大鼠海马SERTmRNA的表达明显下降(P<0.05),而脑组织GFAP蛋白的表达显著升高(P<0.05).与MDMA组比较,提前30 min和MDMA后3 h给予维生素C两组的5-HT含量和海马SERTmRNA的表达无明显改变(P>0.05),而给予MDMA后5 h给予维生素C组的5-HT含量和海马SERTmRNA的表达明显增加(P<0.05);不同时间给予维生素C的3组大鼠脑组织GFAP蛋白的表达均较MDMA组显著降低(P<0.05).结论:MDMA对中枢5-HT系统具有明显的神经毒性;在给予MDMA后5 h给予维生素C对5-HT能系统有保护作用.     

复脑苏I段生殖毒性研究

目的：观察复脑苏对SD大鼠的I段生殖毒性。方法：采用SD大鼠，雌雄各80只，分为3个剂量组（7．5、15．0和30mg／kg）和一个对照组（0．85％生理盐水），每组20只大鼠。雄鼠于交配前28d给药；雌鼠于交配前14d给药，给药至妊娠后第6天。实验组和对照组给药容量为1mL／100g体重，均采用尾静脉给药。雄鼠于交配后剖杀；1／2孕鼠于妊娠第14天剖杀，另1／2自然分娩。观察雄鼠、雌鼠和F1代仔鼠的相关指标。结果：复脑苏在各受试剂量下，对雄性大鼠的精子发生无明显影响，表现为活精子数、精予畸形率、脏器系数与对照组比较无统计学差异（P〉0．05）；病理学检查显示，未引起睾丸、附睾明显的病理学改变。复脑苏在各受试剂量下，对雌性大鼠的生殖功能也未见明显影响，表现为交配率、受孕率、流产率、活胎率、吸收胎率与对照组比较差异无统计学意义（P〉0．05）；也不影响仔鼠的出生存活率和哺育存活率。结论：在受试剂量下复脑苏对雄性和雌性大鼠无生殖毒性。     

羟基脲对大鼠睾丸和附睾的毒性作用

目的 观察羟基脲(HU)对大鼠睾丸和附睾的毒性作用特点.方法 雄性大鼠分别连续10 d腹腔注射100、200和400 mg/kg羟基脲,分别于停药第9、23天处死动物.结果从给药第7天起,200、400 mg/kg组雄性大鼠体重明显下降.停药第9时,病理组织形态学观察显示曲细精管内生精细胞缺失、脱落明显,400 mg/kg组部分管腔甚至出现大量多核巨细胞,附睾出现脓肿.睾丸和附睾组织的病理损害,在停药第23天较第9天更为严重.无论停药第9、23天,前列腺和精囊腺未见明显组织病理学变化.睾丸病理切片TUNEL染色的结果显示给予HU后,各剂景组发生凋亡的细胞明显增多.结论雄性大鼠连续10 d腹腔注射HU 100 mg/kg以上,可以引起睾丸和附睾明显的病理损害,表明HU生殖毒性作用的靶器官是睾丸和附睾,而且停药后一段时间内毒性表现具有延迟性.     

Lactuside B增加大鼠脑缺血后海马和纹状体GRP78 mRNA的表达

目的:探讨高翅果菊提取物Lactuside B对大鼠脑缺血后海马和纹状体GRP78mRNA表达的影响。方法:清洁Ⅱ级SD雄性大鼠,体质量280～320g,随机分为6组,即:模型组、假手术组、阳性药物对照组(尼莫地平1mg·kg-1)、Lactuside B12.5、25和50mg·kg-1组,每组8只。采用大鼠大脑中动脉阻塞法复制脑缺血再灌注损伤模型,所有大鼠均阻塞2h再灌注。各组动物于再灌注后给予腹腔注射相应的实验药物(模型组、假手术组动物给予等体积的纯化水),bid,给药1d和3d后分别处死各组的4只动物取脑备用。神经缺失症状评分法进行神经功能测定;RT-PCR技术分别检测大鼠海马和纹状体不同时间段GRP78mRNA的表达。结果:给药1d和3d后,Lactuside B各剂量组动物的神经行为学评分均降低,与模型组比较均有显著性差异(P<0.05或P<0.01);Lactuside B各剂量组动物海马和纹状体的GRP78mRNA表达均明显增多,与模型组比较差异有显著性(P<0.05或P<0.01);除用药1d时纹状体GRP78mRNA的表达在各组间有量效关系外,其余各组的高剂量组作用较差;海马的Lactuside B各剂量组GRP78mRNA的表达优于阳性对照组(P<0.05或P<0.01),而纹状体只有用药3d时此种作用才明显。结论:Lactuside B的抗脑缺血作用与其持续上调海马和纹状体的GRP78mRNA表达有关。     

转Bt基因大米对大鼠雄性子代生精功能及相关激素水平的影响

目的研究亲代转Bt基因TT51大米暴露对大鼠雄性子代生精功能及相关激素水平的影响。方法亲代雌雄大鼠连续给予含60%对照市售稻花香大米、亲本明恢63大米和转Bt基因TT51大米饲料70 d后,交配产生子代,各组母鼠孕期和哺乳期继续给予相应受试大米饲料。子代雄信大鼠断乳后各组继续给予相应受试饲料70 d后,测定各组子代大鼠睾丸、附睾、前列腺、精囊腺等脏器系数,进行附睾尾精子数量、精子活率和精子畸形率以及血清中性激素水平检测。结果 TT51大米组与亲本明恢63大米组和市售大米组比较,子代雄性大鼠精子各项指标以及血清性激素水平差异均无统计学意义,病理学检查显示各组动物前列腺、睾丸和附睾结构完整清晰,睾丸各级生精细胞排列整齐,未见出血、坏死及精细胞发育异常。结论与对照和亲本相比转Bt基因大米暴露对雄性子代大鼠生精功能和血清性激素水平的影响差异无统计学意义。     

Pharmacokinetics of baicalin-phospholipid complex in rat plasma and brain tissues after intranasal and intravenous administration

The aim of this study is to determine whether baicalin can be transferred along the olfactory pathway to the brain after nasal administration of baicalin phospholipid (BP) complex to rats, thereby circumventing the blood brain barrier. The concentration of baicalin in plasma and different brain tissues (olfactory bulb, cerebral cortex, striatum and cerebellum) were measured by high-performance liquid chromatography (HPLC). The ratios of the area under the concentration-time curve (AUC) values of intranasal to intravenous administrations were 54.21%, 240.59%, 374.71%, and 114.54% in plasma, cerebral cortex, striatum, and cerebellum, respectively. In the olfactory bulb, the AUC values of intranasal to intravenous administrations were 3355.4 +/- 378.8 microg/g-min versus 0 microg/g x min following intravenous administration. The ratios of AUC values of intranasal to intravenous administrations were72.75 %, 240.59 %, 374.71%, 114.54% in plasma, cortex, striatum, cerebellum respetively. The proportion of baicalin in the brain tissues from the olfactory transfer was also calculated, and the result shows that, following intranasal administration, approximately 52.36%-100% baicalin content at 8 h was transported to the brain via the olfactory pathway. In conclusion, the BP complex is transferred into the olfactory bulb via the olfactory pathway in rats, and the BP complex intranasal delivery is a promising approach to protect against cerebral ischemic injury.     

Survival and differentiation of transplanted neural stem cells in mice brain with MPTP-induced Parkinson disease

AIM: To determine survival and differentiation of cultured neural stem cells (NSCs) into viable and functional neurons upon transplantation into mice brain of MPTP-induced Parkinson disease (PD). METHODS: Mouse model of PD was established with two subcutaneous (sc) injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 40 mg/kg) twice, 16h apart. NSCs isolated from rat embryo midbrain were cultured in clonal density. After labeled with 5-bromo-2'-deoxyuridine (BrdU), the NSCs were transplanted into the uni-or bi-lateral striatum of PD mouse. Tyrosine hydroxylase (TH) immunofluorescence was used to evaluate the toxicity of MPTP on the neural cells in the substantia nigra. Immunohistology and laser confocal microscope were used to detect the survival and differentiation of transplanted NSCs. RESULTS: The cultured NSCs generated neurospheres and differentiated into neuron and astrocyte. It indicated that the cultured NSCs were multipotent and self-renewal in vitro. TH-positive neural cells were     

移植的神经干细胞在MPTP诱导的帕金森病小鼠脑内的存活与分化

AIM: To determine survival and differentiation of cultured neural stem cells (NSCs) into viable and functional neurons upon transplantation into mice brain of MPTP-induced Parkinson disease (PD). METHODS: Mouse model of PD was established with two subcutaneous (sc) injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP,40mg/kg) twice, 16h apart. NSCs isolated from rat embryo midbrain were cultured in clonal density.After labeled with 5-bromo-2'-deoxyuridine (BrdU), the NSCs were transplanted into the uni-or bi-lateral striatumof PD mouse. Tyrosine hydroxylase (TH) immunofluorescence was used to evaluate the toxicity of MPTP on the neural cells in the substantia nigra. Immunohistology and laser confocal microscope were used to detect the survival and differentiation of transplanted NSCs. RESULTS: The cultured NSCs generated neurospheres and differentiated into neuron and astrocyte. It indicated that the cultured NSCs were multipotent and self-renewal in vitro.TH-positive neural cells were significantly reduced in the substantia nigra. Immunohistology showed that the uni-or bi-lateral transplanted NSCs survived in the brain of PD model mouse. Laser confocal microscope indicated that some transplanted NSCs could properly differentiate into targeted TH-positive neural cells in vivo. CONCLUSION:The transplanted multipotent NSCs could survive and differentiate into functional dopamine neurons.     

Drug brain distribution following intranasal administration of Huperzine A in situ gel in rats

AIM: To determine the uptake extent of Huperzine A (Hup A) into the brain after intranasal administration of Hup A in situ gel to rats, and to compare the pharmacokinetic parameters between intranasal administration and iv and po. METHODS: Hup A was administered to male Sprague-Dawley rats via nasal, iv and oral routes at the dose of 166.7, 166.7, and 500 mug/kg, respectively. Blood and brain tissue samples including the cerebrum, hippocampus, cerebellum and olfactory bulb were collected, and the concentrations of Hup A in the samples were assayed by HPLC. The area under the concentration-time curve (AUC(0-->6 h)) and the ratio of the AUC(brain) to the AUC(plasma) (drug targeting efficiency, DTE) were calculated to evaluate the brain targeting efficiency of the drug via 3 administration routes. RESULTS: The AUC(0-->6 h) of the drug in the cerebrum, hippocampus, cerebellum, left olfactory bulb and right olfactory bulb after intranasal administration of the Hup A in situ gel were 1.5, 1.3, 1.0, 1.2, and 1.0 times of those after iv administration of the injection, and 2.7, 2.2, 1.9, 3.1, and 2.6 times of those after administration of the oral formulation. The AUC (brain0-->6 h)/AUC(plasma0-->6 h) of Hup A in the cerebrum, hippocampus and left olfactory bulb following the intranasal administration dose were significantly higher (P<0.05) than the iv dose. CONCLUSION: Intranasal delivery showed a viable, non-invasive strategy for delivering the drug into brain.     

Pharmacological characterization of binding sites identified in rat brain following in vivo administration of [3H]-spiperone.

[3H]-spiperone is commonly used to label dopamine receptors in vitro in brain tissue. However, spiperone also interacts with brain 5-hydroxytryptamine and noradrenaline receptors. In vivo, [3H]-spiperone has been used for identifying dopamine receptors in both animals and man but the nature of the sites identified is unknown. The in vivo administration of [3H]-spiperone to rats leads to a selective accumulation of radioactivity in the olfactory lobes, tuberculum olfactorium, nucleus accumbens, striatum, substantia nigra, hippocampus, frontal cortex and hypothalamus, when compared to the cerebellum. In vivo drug displacement studies suggest that the binding of [3H]-spiperone in these areas may be to dopamine, 5-HT or noradrenaline receptors. [3H]-spiperone in vivo mainly labels dopamine receptors in striatum, tuberculum olfactorium, hypothalamus, substantia nigra and olfactory lobes. However, in the frontal cortex and nucleus accumbens specific binding involves not only dopamine receptors but also 5-HT and/or noradrenaline receptors. Interpretation of in vivo studies in man using radioactive spiperone and its derivatives must take into account the fact that this ligand only labels dopamine receptors in some brain areas.     

The interaction between ethanol and pregnanolone at induction of anaesthesia investigated with a threshold method in male rats.

1. An anaesthesia threshold was used to investigate the pharmacodynamic and pharmacokinetic interactions between ethanol and pregnanolone in male rats. 2. The criterion to determine threshold doses of pregnanolone was the first burst suppression of 1 s in the EEG. 3. Ethanol (0.5, 1.0, 1.5 and 2.0 g kg(-1)) was injected i.p. 15 min before pregnanolone infusion. Trunk blood, serum, cortex, cerebellum, hippocampus, striatum, brain stem, fat and muscle tissues obtained at criterion were used to determine ethanol (blood) and pregnanolone. Ethanol reduced threshold doses in a dose dependent linear manner. A similar reduction of pregnanolone tissue concentrations was only found in brain stem and striatum. Deviations consisted of larger decreases in serum, cerebellum and hippocampus after 0.5 g kg(-1) ethanol and in cerebellum, cortex and hippocampus after 2.0 g kg(-1) of ethanol. Positive correlations between dose and concentration of pregnanolone was recorded in brain stem, hippocampus, cerebellum and cortex. A kinetic component influenced the concentration in cortex. There was a correlation between dose and serum concentration of pregnanolone only after ethanol. In the muscle 0.5 g kg(-1) ethanol had no influence on pregnanolone concentration. 4. The linear, additive pharmacodynamic interaction could involve the GABA ionophore. A pharmacokinetic interaction was found in cortex. The retained high uptake of pregnanolone in muscle (after 0.5 g kg(-1)) corresponded to losses in other tissues (including serum). The reduced uptake of pregnanolone in cerebellum, cortex and hippocampus (after 2.0 g kg(-1)) was not due to a corresponding change in serum concentration. It was probably due to a reduced blood flow.     

石杉碱甲鼻用原位凝胶的制备及其经鼻脑靶向性评价

目的探索利用鼻腔嗅觉区的鼻-脑通道开发经鼻脑靶向给药系统的可行性。方法用阳离子敏感性成胶辅料结冷胶，采用pH梯度沉淀法制备了石杉碱甲鼻用原位凝胶。以市售片剂和注射液为对照，用小脑延髓池插管法采集脑脊液，股动脉插管取血，测定其在大鼠脑脊液和血中药物动力学参数；用组织匀浆法，测定其在大鼠脑组织中的分布；用Morris水迷宫法、跳台法和避暗法试验其对大鼠和小鼠模型的药效。结果大鼠鼻腔给药血浆AUC_{0→6 h}为静注的0.94倍，但脑脊液AUC_{0→6 h}为静注和灌胃的1.3和2.3倍；大鼠鼻腔给药后大脑、海马、小脑、左右嗅球的AUC_{0→6 h}分别为静注的1.5，1.3，1.0，1.2和1.0倍，为灌胃的2.7，2.2，1.9，3.1和2.6倍。药效学研究表明以1/4～1/2口服剂量鼻腔给药与口服等效，与药动学结果相符。结论石杉碱甲原位凝胶鼻腔给药较静注和灌胃显著增加了药物在脑内，特别在其改善记忆障碍作用的靶部位——大脑和海马的分布，提高了药物的脑靶向性。     

Brain pharmacokinetics and tissue distribution of tetrahydropalmatine enantiomers in rats after oral administration of the racemate

Tetrahydropalmatine (THP), a racemic mixture, is a biologically active ingredient isolated from a traditional Chinese herb Rhizoma Corydalis (yanhusuo). The main objective of this study was to determine the brain pharmacokinetics and tissue distribution of THP enantiomers in rats after oral administration of racemic THP (rac-THP). Rats (5 animals/group/per time) were given a single oral dose of rac-THP and killed after different post-treatment times. The concentrations of THP enantiomers in plasma, cortex, cerebellum, diencephalon, brain stem, striatum and hippocampus were measured using a validated chiral high performance liquid chromatographic (HPLC) method coupled with an achiral column. The pharmacokinetic profiles of the two enantiomers in six brain regions were significantly different. The peak concentrations (Cmax) and AUC(0-infinity) values of the (-)-enantiomer were significantly greater than the corresponding values for the (+)-enantiomer while the striatum contained the highest peak concentrations compared with the plasma and other brain regions. The tissue distribution studies also revealed significant differences between the two enantiomers in all tissues except the lung. The highest concentrations of both enantiomers were found in the liver. The (-)/(+)-THP ratios in six brain regions and other tissues were consistent with that observed in plasma indicating that the stereoselective disposition of THP in rat brain and other tissues reflects the situation in plasma.     

慢性吗啡处理对大鼠不同脑区前强啡肽原mRNA表达水平的下调作用

目的·· :观察慢性腹腔注射(ip)吗啡对大鼠下丘脑、海马、纹状体中前强啡肽原mRNA(PPDmRNA)表达的影响。方法·· :20只SD大鼠随机分为吗啡依赖组和对照组;依赖组大鼠ip 吗啡12d,建立吗啡依赖模型 ,对照组注射生理盐水。于d13断头处死大鼠 ,取出下丘脑、海马、纹状体组织,以NorthernBlot印迹杂交检测其中PPDmRNA的表达水平。结果·· :依赖组大鼠下丘脑、海马、纹状体中PPDmRNA的表达水平分别下降至51.5 %±s4.7 %、81.3 %±s4.5 %、62.3%±s4.5 % ,明显低于生理盐水对照组 (P<0.05)。结论·· :吗啡依赖大鼠下丘脑、海马、纹状体中PPDmRNA的表达水平较生理盐水对照组有显著下降,不同脑区PPDmRNA的表达水平与吗啡耐受和依赖的神经生物学机制有关     

白藜芦醇对慢性帕金森病6-OHDA模型大鼠iNOS mRNA及HO-1 mRNA表达的影响

目的观察白藜芦醇能否通过抑制诱导型一氧化氮合成酶(iNOS)mRNA及血红素加氧酶-1(HO-1)mRNA的表达对慢性帕金森病(PD)6-羟基多巴胺(6-OHDA)模型大鼠产生保护效应。方法经筛选无旋转行为的SD大鼠60只,随机选20只分为假手术组及正常给药组(白藜芦醇20 mg.kg-1.d-1);应用6-OHDA纹状体内注射制作PD模型大鼠40只,随机分为模型组和白藜芦醇10、20和40 mg.kg-1.d-1组,每日灌胃给药1次,连续10 wk。电镜下观察黑质神经元超微结构的改变,real-time PCR法检测大鼠黑质部iNOS mRNA及HO-1 mRNA的表达。结果电镜结果显示白藜芦醇治疗组能改善6-OHDA导致的大鼠黑质多巴胺能神经元超微结构的损伤。与模型组比较,白藜芦醇治疗组iNOS mRNA、HO-1 mRNA的表达均明显降低(P<0.01)。结论白藜芦醇对慢性帕金森病6-OHDA模型大鼠具有保护作用,其机制与抑制iNOS mRNA和HO-1 mRNA的表达有关。