雌激素对阿尔茨海默病大鼠模型MAPK蛋白表达的影响

目的探讨雌激素对阿尔茨海默病(AD)大鼠模型学习记忆能力及丝裂霉原活化的蛋白激酶(MAPK)蛋白表达的影响。方法30只大鼠行卵巢切除术(OVX)后,均分成OVX组和雌激素替代治疗组(ERT),然后采用1μlofAβ1～40(10μg/μl)立体定位单侧海马内注射建立AD动物模型,通过水迷宫实验检测动物模型的学习、记忆能力;免疫组化检测MAPK蛋白表达情况。结果ERT组AD动物模型的水迷宫逃避潜伏期较OVX组明显缩短(P<0.05),同时ERT组AD动物模型的海马CA1、CA3区的MAPK表达上调(P<0.05)。结论雌激素可以改善AD动物模型的认知功能,其神经保护作用可能与上调海马MAPK表达有关。     

雌激素对阿尔茨海默病去势雌性SD大鼠学习记忆能力的影响

目的观察雌激素对阿尔茨海默病(AD)大鼠学习记忆能力的影响。方法首先采用Aβ1～40,1μL(10μg/μL)立体定位SD大鼠单侧海马内注射建立AD动物模型,二周后双侧卵巢切除术(OVX)制备去卵巢大鼠模型后给予雌激素替代治疗(ERT),最后通过Morris水迷宫观察动物模型的学习、记忆能力变化情况。结果 ERT组AD动物模型的水迷宫逃避潜伏期和目标象限游泳时间比OVX组明显缩短(P0.05)。结论雌激素具有改善AD大鼠模型认知功能的作用。     

雌激素对SAMP8小鼠学习记忆及海马CA1区神经元的影响

目的 观察雌激素对SAMP8鼠学习记忆及海马神经元的影响. 方法 将6月龄SAMP8鼠45只分为假手术组(sham组)、去卵巢组(OVX组)和去卵巢+雌激素组(OVX+E组)3组,并用同龄正常老化SAMR1小鼠作为同源对照组.采用Morris水迷宫实验检测小鼠学习记忆能力,苏木素-伊红染色和免疫组织化学显示海马CA1区神经元及神经型一氧化氮合酶(nNOS)阳性神经元的变化,流式细胞术检测其nNOS的表达量. 结果 OVX组与sham组相比,逃避潜伏期明显延长(P<0.05),跨越平台次数显著减少(P<0.05).雌激素补充治疗能改善学习记忆能力,与sham组比较差异无统计学意义(P>0.05);OVX组海马CA1区神经元病变严重,且CA1区nNOS阳性神经元的数量、吸光度和海马nNOS荧光指数(FI)值均低于sham组(P<0.05);给予雌激素后,OVX+E组各项实验结果与OVX组相比差异有统计学意义(P<0.05),与sham组相比,差异无统计学意义(P>0.05). 结论 雌激素能够改善小鼠的学习记忆能力,有效保护海马CA1区的神经元,提高海马CA1区nNOS阳性神经元的表达.     

雌激素及其拟似物对去卵巢大鼠海马Synaptophysin、Parvalbum in及Galbindin-D28K的影响

雌激素(E)替代疗法(ERT)在AD防治过程中取得良好的效果,其机制可能对海马皮层等有影响作用。采用卵巢切除术(OVX)动物模型,观察E及其拟似物(ZR)对海马Synaptophysin(Syn)及Parvalbumin(PV)、Calbindin-D28K(CaBP)的影响。实验用雌性Wistar大鼠(3月龄,体重240±10g),行OVX,假手术组只暴露卵巢而不切除,大鼠在OVX术后两周开始给药(给药5周,3d一次,im,200μg/只)。动物分组如下:1假手术组 橄榄油;2OVX 橄榄油;3OVX E;4OVX ZR。给药结束后,心脏灌流固定,取脑冰冻切片(20μm或40μm),进行Syn、PV、CaBP免疫组化和图像分析。…     

雌二醇对去卵巢大鼠下丘脑5-HT_(1A)和5-HT_(2A)受体亚型mRNA表达的影响

观察17β-雌二醇(17β-estradioI,E2)对去卵巢大鼠下丘脑5-HT1A和5-HT2A受体mRNA表达的影响的时间效应。实验动物分为假去卵巢对照组(OVX+S组)和去卵巢组(OVX)。去卵巢组大鼠又分为雌激素处理组(OVX+E+组)和无雌激素处理组(OVX+E-组),分别在处理后3、6、9和12 d时,采用反转录-聚合酶链式反应(RT-PCR)方法观察5-HT1A和5-HT2A受体mR-NA在大鼠下丘脑的表达。结果显示:5-HT1A和5-HT2A受体mRNA在所有大鼠下丘脑均有表达;5-HT1A受体mRNA在3、6和9 d的OVX+E-组大鼠下丘脑的表达水平明显高于同时间点的OVX-E+组,而5-HT2A受体mRNA在6、9和12 d的OVX+E-组下丘脑的表达量也显著高于同时间点的OVX+E+组。本文结果表明去卵巢后大鼠下丘脑5-HT1A和5-HT2A受体亚型mRNA表达水平升高,17β-雌二醇可下调两种受体的表达。     

雌激素改善卵巢切除合并慢性铝中毒对大鼠心脏Cx43表达和金属元素变化的影响

目的 探讨雌激素治疗卵巢切除合并慢性铝中毒大鼠,对心脏间隙连接蛋白43(Cx43)表达和金属离子含量的影响. 方法 40只6月龄雌性SD大鼠,随机分为卵巢假切除组(Sham组),卵巢切除组(OVX组)、卵巢切除合并慢性铝中毒组(OVX+Al组)和卵巢切除合并慢性铝中毒及尼尔雌醇灌胃组(OVX+Al+E2组).于术后3个月,利用离子体发射光谱仪测定心脏金属元素含量,采用免疫组织化学和图像分析法观测心肌细胞Cx43表达.结果 1. Cx43表达:Sham组心房肌Cx43遍布于心肌细胞侧面连接和端闰盘处.心室肌分布于心肌闰盘处.OVX组心房肌的Cx43颗粒部分由细胞侧-侧连接处移至闰盘处或杂乱排列,心室肌Cx43由闰盘处移至细胞侧-侧连接处或杂乱地无序排列,少部分出现在细胞质中,OVX+Al组Cx43排列类似于OVX组,且更加紊乱.OVX+Al+E2组心房肌Cx43回复正常分布,但心室肌未发现回复.2.图像分析结果,各组大鼠心肌细胞Cx43的面积构成比比较无显著差异.3.金属元素含量:在Sham组,金属元素在心脏含量的排列顺序如下:Mg＞Ca＞Fe＞Zn＞Al＞Si＞Cu＞Mn＞Se和Cd.各组间比较具有显著差异的是:与Sham组比较,OVX组Zn降低;OVX+Al+E2组Al、Cd、Si、Se均升高;OVX+Al组与OVX组比较,Si升高、Zn降低.OVX+Al+E2组与OVX+Al组比较, Cd、Mn、Se升高. 结论雌激素改善卵巢切除及加铝后引起的心脏金属元素含量改变和心肌细胞间隙连接蛋白Cx43重构.     

雌激素对卵巢摘除大鼠心内神经节细胞Bcl-2和Bax表达的影响

本实验建立了去卵巢和雌激素替代疗法动物模型,用免疫组织化学SABC法结合图象分析方法,观察大鼠心内神经节细胞中Bcl-2和Bax的变化,探讨雌激素对卵巢摘除大鼠心内神经节细胞中Bcl-2和Bax表达的影响。去卵巢(OVX)大鼠心内神经节细胞中Bcl-2的表达较正常对照组明显减弱(P<0.05),雌激素替代治疗组大鼠心内神经节中Bcl-2的表达与正常对照组相比无显著性差异(P>0.05),而较卵巢摘除组显著增高(P<0.05);卵巢摘除后同时给予特异性雌激素受体阻断剂(TAM)和17β-雌二醇(OVX+TAM+ERT)组大鼠心内神经节中Bcl-2的表达较正常对照组显著减弱(P<0.05),但与OVX组无显著性差异(P>.05)。各组中Bax的表达无显著性差异(P>0.05)。实验结果提示雌激素能上调大鼠心内神经节细胞中Bcl-2的表达,但对Bax的表达无影响。     

雌激素对大鼠血管平滑肌细胞囊泡素-1基因表达的影响

目的:探讨雌激素对血管平滑肌细胞囊泡素-1基因表达的影响。方法:取Wistar雌性大鼠,分为3组:假手术组,卵巢切除后皮下埋植雌激素组 (OVX+E组)及卵巢切除后皮下埋植安慰剂组(OVX+V组)。用药2周后处死大鼠,剥离主动脉平滑肌组织,提取总RNA进行半定量RT-PCR分析,检测雌激素对囊泡素-1(caveolin-1)基因表达的影响。为进一步明确雌激素是否直接调节血管平滑肌细胞caveolin-1基因表达,又采用100 nmol/L 17β-雌二醇(17β-E₂)处理培养的大鼠血管平滑肌细胞24 h,通过Northern blot分析检测雌激素对细胞caveolin-1 mRNA表达的影响。结果:OVX+E组大鼠主动脉平滑肌组织caveolin-1基因表达量明显高于OVX+V组,17β-E₂处理的培养细胞中caveolin-1基因mRNA表达量高于未用药的培养细胞。 结论:雌激素可促进血管平滑肌细胞caveolin-1基因表达,反映了雌激素心血管作用机理的一个方面。     

雌激素对阿尔茨海默病模型大鼠学习记忆的影响

目的:探讨雌激素对阿尔茨海默病(Alzheimer’s disease,AD)模型大鼠学习记忆能力的影响。方法:选取雌性SD大鼠24只,随机分为假手术组、卵巢切除组(ovariectomy,OVX)、OVX+苯甲酸雌二醇组(estradiolbenzoate,EB),每组8只。于海马注射Aβ1-42建立AD大鼠模型,通过Morris水迷宫观察大鼠的学习记忆能力,同时用ELISA检测脑组织超氧化物歧化酶(super oxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)、乙酰胆碱酯酶(acetylcholine esterase,ACh E)的活性,用免疫组化分析神经元型一氧化氮合酶(n NOS)并测定其OD值。结果:与OVX组比较,OVX+EB组逃避潜伏期明显缩短(P0.05),原平台象限活动时间明显增加(P0.05),穿越原平台次数明显增多(P0.05)。雌激素作用还提高大鼠脑组织SOD、ACh E和n NOS活性,降低MDA活性(P0.05)。结论:研究表明雌激素可改善AD模型大鼠的学习记忆能力,其机制可能通过提高脑组织SOD、ACh E和n NOS活性,降低MDA活性有关。     

梓醇通过上调p-Akt表达抑制慢性脑缺血诱导的大鼠脑白质损伤

目的 探讨梓醇对慢性脑缺血诱导的大鼠脑白质损伤的保护作用及其与Akt通路之间的相关性.方法 成年雄性Wistar大鼠18只,随机分为假手术组(Sha组),生理盐水处理组(Veh组)和梓醇处理组(Cat组),每组6只.以永久性结扎双侧颈总动脉诱导大鼠慢性脑缺血,Veh组和Cat组大鼠分别腹腔注射生理盐水和梓醇(5 mg/kg),连续10d.慢性缺血30 d后,采用卢卡斯快蓝(LFB)染色法和免疫组织化学染色法检测梓醇对脑白质少突胶质细胞凋亡、髓鞘损伤及p-Akt表达的影响.结果 在Veh组的脑白质中,少突胶质细胞凋亡和髓鞘损伤程度明显增加,与Sha组比较有显著性差异(P＜0.01).梓醇治疗后能明显降低少突胶质细胞凋亡和髓鞘损伤,上调p-Akt表达,其结果与Veh组比较均有显著性差异(P＜0.05).结论 梓醇可通过上调p-Akt的表达抑制慢性脑缺血诱导的脑白质损伤.     

雌激素对卵巢摘除大鼠心内神经节细胞胆碱乙酰基转移酶和一氧化氮合酶表达的影响

目的：探讨雌激素对卵巢摘除大鼠心内神经节细胞中神经递质的影响。方法：建立去卵巢(OVX)和雌激素替代疗法动物模型，2个月后用免疫组化结合图象分析方法观察大鼠心内神经节细胞中胆碱乙酰基转移酶(ChAT)和一氧化氮合酶(NOS1)的变化。结果：在OVX大鼠心内神经节细胞中ChAT和NOS1较正常对照组明显减少，雌激素(E2)替代治疗组与正常对照组相比无明显变化，OVX 雌激素受体拮抗剂(TAM)组较正常对照组显著减少，但与OVX组无明显差异。结论：雌激素能上调大鼠(OVX)心内神经节细胞中ChAT和NOS1的表达，雌激素可能够通过对心内神经节细胞中神经递质的调节，间接发挥对心血管功能的调节作用。     

三羟异黄酮对去势雌性大鼠主动脉壁NF-κB的表达影响

目的：观察三羟异黄酮(GST)对去势雌性大鼠主动脉壁核因子-Kappa B表达的影响。 方法： 将40只成年雌性大鼠随机分成4组：(1)假手术组，(2)去势组，(3)雌激素组，(4)GST组。给药6周后处死大鼠。免疫组化法检测主动脉壁中NF-κB p65的表达。 结果： 去势大鼠主动脉壁NF-κB p65的表达明显多于假手术组，细胞核呈阳性表达；雌激素组和GST组NF-κB p65的表达明显少。去势组大鼠伴有主动脉血管动脉粥样硬化的病理改变。 结论： GST可抑制NF-κB p65在大鼠主动脉的表达，减轻动脉粥样硬化的病理改变。     

去卵巢和雌激素替代治疗对心肌细胞基因表达谱的影响

目的：本实验通过高通量的cDNA微阵列技术，研究去卵巢和雌激素替代治疗对心肌细胞基因表达谱的影响，寻找雌激素的靶基因。方法:用 1 400 个基因构建的cDNA微阵列检测假手术组（Ⅰ）、去卵巢组（Ⅱ，去势组）和雌激素替代治疗组（Ⅲ，替代组）3组SD雌鼠心肌组织的基因表达差异,随机选2个基因用半定量RT-PCR验证检测结果。结果:假手术组和去势组共检出心肌差异表达的基因177个，其中去卵巢导致上调的基因91个，下调的基因86个；去势组和替代组共检出心肌差异表达的基因164个，其中雌激素替代治疗后导致上调的基因113个，下调的基因54个。Ⅰ/Ⅱ和Ⅲ/Ⅱ比较，相同的差异表达基因54个，雌激素明显影响心肌膜通道和载体（18个）、细胞受体（9个）、信号转导相关基因（7个）和细胞代谢（6个）的mRNA水平。而大部分基因（45个）是在去势组表达下调，在雌激素替代组表达上调。RT-PCR实验证实了cDNA微阵列结果 。结论：长期雌激素替代治疗明显影响心肌细胞膜通道和载体、信号转导、细胞受体和细胞代谢等相关基因的表达。长期雌激素替代治疗可通过增加Na+,K+-ATPase和Na+/H+交换蛋白的基因表达，稳定心肌细胞内Na+和K+的浓度。雌激素还可抑制多巴胺受体基因的表达，预防心肌肥大、充血性心衰等心脏疾病的发生。     

新生大鼠缺氧缺血脑白质损伤模型学习记忆能力的变化

目的通过缺氧、缺血法建立新生大鼠脑白质损伤(WMI)模型,评价大鼠各个生长时期的学习记忆能力及髓鞘碱性蛋白(MBP)表达变化。方法新生4日龄SD大鼠100只随机分为对照组和缺氧、缺血WMI组,应用HE染色法观察脑组织病理学改变。于术后4周、8周与12周分别观察大鼠神经行为学和学习记忆能力改变,并应用免疫荧光染色法和Western blotting法观察MBP在大鼠脑内的定位定量表达变化。结果 HE染色显示,WMI组大鼠出现缺氧、缺血脑白质损伤病理改变。WMI组大鼠神经行为学及学习记忆能力较对照组减弱,差异具有统计学意义(P0.01)。WMI组各时间点的MBP表达量较对照组降低,差异具有统计学意义(P0.01)。结论新生4日龄SD大鼠发生缺氧、缺血脑白质损伤后,各个生长时期的学习记忆能力均减弱,MBP蛋白表达均减少,推测学习记忆能力减弱可能与MBP蛋白表达减少有关。     

脑白质损伤模型中Lingo-1的动态变化

BACKGROUND:Lingo-1 has been identified as a negative regulator of oligodendrocyte differentiation and myelination, which may be closely related to the white matter damage, but there is no systematic report on the dynamic changes of Lingo-1 after white matter damage.  OBJECTIVE: Toexplore the dynamic expression of Lingo-1 at different time points after white matter injury in newborn rats. METHODS:Seventy-eight Sprague-Dawley rats aged 3 days old were equally and randomly divided into sham operation group and model group. In the model group, models of white matter injury were established by unilateral ligation of the right common carotid artery combined with hypoxia. In the sham operation group, the right common carotid artery was isolated only, without ligation or hypoxia.  RESULTS AND CONCLUSION:At 7 days after model induction, hematoxylin-eosin staining and immunohistochemical staining for myelin basic protein showed that a selective white matter injury was seen at the injury site of a rat model, suggesting successful model establishment. Fluorescent quantitative PCR and western blot assay results demonstrated that the expression levels of Lingo-1 mRNA and protein were significantly up-regulated at 1 day and reached a peak at 7 days post-surgery. After 7 days, above expression was gradually decreased and the up-regulation of Lingo-1 protein lasted to the 28 days post-surgery compared to the sham operation group. These results show that Lingo-1 protein was closely related to the brain white matter injury.     

Estrogen replacement reverses ovariectomy-induced vaginal hyperalgesia in the rat

OBJECTIVES: The loss of ovarian function in women through aging or oophorectomy is often associated with the development of vaginal hyperalgesia that can be alleviated with estrogen replacement. This study examined if ovariectomy in rats would similarly give rise to vaginal hyperalgesia, and, if so, whether estrogen replacement would alleviate it. METHODS: Female rats were trained to perform an operant response to escape vaginal distention delivered by inflating a balloon located in mid-vaginal canal. Percent escape responses to eight different volumes of distention measured in normally cycling rats were compared with measures made in the same rats following ovariectomy (OVX) or sham ovariectomy (shamOVX), and then, in the OVX group, estrogen replacement (OVX+E2). Pressures exerted by the eight volumes on the vaginal wall were also measured, thereby permitting assessment of vaginal tone. RESULTS: Whereas overall escape response percentages after OVX, but not shamOVX, were significantly higher to the largest six distention volumes compared with responses during cycling, there were individual differences in the amount of hyperalgesia. Following OVX+E2, escape response percentages decreased in all but one rat. Vaginal tone after OVX, shamOVX or OVX+E2 did not differ from overall vaginal tone in cycling rats. CONCLUSIONS: Ovariectomy in rats evokes a variable amount of vaginal hyperalgesia that can be alleviated by estrogen replacement in most cases. Thus, the ovariectomized rat appears to provide a useful model for the study of mechanisms underlying the dyspareunia that is associated with loss of ovarian function in women.     

Effects of ovariectomy and estrogen on skeletal muscle function in growing rats

This study examined the effect of estrogen replacement on soleus muscle size and contractile function in ovariectomized rats during physiological growth. Seven week old female Sprague-Dawley rats were assigned to one of three treatment groups: (1) control animals (SHAM), (2) ovariectomized animals without estrogen replacement (OVX/CO), and (3) ovariectomized animals with 17 beta-estradiol replacement (OVX/E2). OVX/CO and OVX/E2 animals were pair-fed to SHAM animals to rule out the potentially confounding effect of differences in food intake. Rats were sacrificed 4 weeks after surgery and the soleus muscle was removed for analysis. Estrogen replacement reduced body weight, relative body weight gain, and soleus muscle fiber size despite all groups having a similar food intake. Ovariectomy alone had no effect on any of these parameters suggesting that estrogen may inhibit skeletal muscle growth when it is the only ovarian hormone present. Neither ovariectomy nor estrogen replacement affected maximal specific isometric force. Estrogen replacement increased half relaxation time. Ovariectomy resulted in a reduction in time to peak tension that was reversed with estrogen replacement. This reduction was not accompanied by a change in myosin heavy chain composition implying that calcium handling may have been altered. Results from this study suggest that estrogen affects skeletal muscle growth and twitch kinetics.