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1.
目的研究雌性大鼠脑老化过程中脑内类固醇受体辅助活化因子(SRC-1)表达的变化。方法硫酸镍铵增强显色的免疫组化SP法。结果SRC-1免疫阳性产物广泛分布于脑内,免疫阳性产物主要位于细胞核,但是在个别主要与运动有关的核团则明显位于细胞胞膜或胞浆。在成年,最高表达见于大脑皮质大部、海马、桥核、前嗅核、网状外侧核、小脑蒲肯野细胞等部位;中等强度的表达见于隔区、丘脑和脑干,较低水平的表达见于某些下丘脑和脑干的核团。和成年的表达水平相比,老年大鼠的前嗅核、斜角带垂直部、基底神经节、杏仁皮质后核、黑质、脑桥、网状外侧核和小脑浦肯野细胞等部位的表达显著下降,但是在大脑皮质、下丘脑和丘脑以及脑干的很多部位基本保持不变,在极个别核团甚至有所上升。结论SRC-1在大鼠脑内的表达比较广泛,可能参与了对多种重要脑功能的调节;老年脑内主要与运动调控和学习记忆有关脑区内SRC-1表达的降低提示SRC-1可能在脑老化导致的学习记忆障碍以及帕金森综合征等神经退行性疾病中有重要意义。核外SRC-1主要见于与运动有关的核团,提示SRC-1有可能通过第二信使途径发挥对运动功能的快速调节。  相似文献   

2.
目的研究类固醇受体辅助活化因子(steroid receptor coactivator-1,SRC-1)在成年雄性大鼠脑内的表达。方法采用硫酸镍铵增强显色的免疫组化技术研究大鼠海马内SRC-1的表达情况。结果SRC-1主要在细胞核内表达,但是在某些核团,尤其是与运动调节有关的核团,可以在细胞核外表达,如胞浆、胞膜甚至突起内。最强表达见于基底前脑的斜角带垂直部、下丘脑弓状核与网状外侧核;高水平的表达见于前嗅核、海马、丘脑和下丘脑部分核团、桥核、脚间核与小脑浦肯野细胞;中等水平的表达见于大部分大脑皮质结构和杏仁复合体以及丘脑,低水平的表达见于中脑、脑桥和延髓大部份。结论SRC-1在成年雄性大鼠脑内的表达比较广泛,可能参与了对多种重要脑功能的调节,如学习记忆、神经干细胞分化发育、神经内分泌与神经免疫、生殖、信息整合与感觉和运动。另外,在大部分脑区SRC-1可能以经典的基因型方式发挥作用,但是,在部分核团也能以通过第二信使的非基因型方式发挥作用。  相似文献   

3.
目的观察姜黄素对糖尿病脑病大鼠胰岛素样生长因子1(IGF-1)、胰岛素样生长因子受体(IGF-1R)表达的影响,分析姜黄素的脑保护作用机制。方法实验动物分为4组:正常对照组(A组)、正常姜黄素组(B组)、糖尿病脑病组(C组)和姜黄素治疗组(D组)。以大鼠一次性腹腔注射链脲佐菌素(STZ)建立糖尿病脑病模型,姜黄素持续灌胃12周。观察大鼠的体质量、血糖、糖化血红蛋白变化,采用免疫组化、RT-PCR法检测IGF-1及IGF-1R表达的变化。结果与A组和B组大鼠相比,C组大鼠血糖、糖化血红蛋白明显增高,体质量下降,海马区IGF-1表达明显减少(P<0.05),同样海马神经元IGF-1R表达减少(P<0.05)。经姜黄素治疗后,D组大鼠糖化血红蛋白下降,体质量增加,血糖变化不大,海马神经元IGF-1表达增多(P<0.05),随之海马神经元IGF-1R表达增多(P<0.05)。结论大鼠海马IGF-1/IGF-1R表达的减少可能在糖尿病脑病发病机制中发挥着重要的作用,姜黄素有脑保护作用,其机制可能是通过调控IGF-1信号通路调节实现的。  相似文献   

4.
 目的: 研究RNA干扰(RNAi)介导的胰岛素样生长因子1受体 (IGF1R) 基因沉默对肝癌细胞生长、迁移与侵袭的影响。方法: 设计并筛选抑制IGF1R mRNA表达效率最高的siRNA序列,构建该序列的慢病毒表达载体,转染293T细胞进行病毒包装。将包装好的慢病毒感染Huh7和Hep3B肝癌细胞,筛选沉默 IGF1R 基因表达的稳定细胞株。将上述稳定细胞株扩大培养,检测细胞IGF1R mRNA表达变化,细胞生长、迁移与侵袭能力变化,以及Ki-67、p-AKT、p-ERK1、Gli1、β-catenin、cyclin D1、p21、BCL-XL的蛋白表达水平变化。结果: 与空白及阴性对照组比较,感染携带 IGF1R 干扰序列慢病毒的Huh7和Hep3B肝癌细胞IGF1R mRNA表达水平显著下调,细胞增殖活性明显降低,细胞凋亡显著增加,细胞迁移和侵袭能力明显受到抑制,细胞中IGF1R、Ki-67、p-AKT、p-ERK1、Gli1、β-catenin、cyclin D1、p21及BCL-XL蛋白表达水平均显著降低。结论: RNAi介导的 IGF1R 基因沉默可明显抑制Huh7和Hep3B肝癌细胞生长及恶性生物学特征,这可能与IGF1R表达水平显著下调而引起上述调控细胞增殖、抗凋亡基因以及相关信号通路基因的蛋白表达水平显著降低有关。  相似文献   

5.
目的:探讨慢病毒介导的靶向沉默胰岛素样生长因子1型受体(IGF-1R)的siRNA对人子宫内膜癌细胞迁移和侵袭功能的影响和可能机制。方法:针对IGF-1R基因设计siRNA,筛选出最有效的siRNA进行慢病毒包装扩增。转染人子宫内膜癌HEC-1B细胞后分别用real-timePCR和Westernblotting方法验证其沉默效率,平板克隆法检测其克隆形成情况,Transwell小室方法检测细胞迁移和侵袭情况,real-timePCR检测基质金属蛋白酶2(MMP-2)和MMP-9mRNA水平的变化。结果:筛选有效siRNA转染子宫内膜癌HEC-1B细胞后,IGF-1R的mRNA水平下降81%,蛋白表达水平下降91.5%。沉默IGF-1R基因后,HEC-1B细胞克隆形成能力下降,迁移和侵袭能力下降,与对照组和转染阴性组相比有显著差异(P<0.05);MMP-2和MMP-9mRNA表达水平下降(P<0.05)。结论:在人子宫内膜癌HEC-1B细胞中下调IGF-1R水平能降低MMP-2和MMP-9mRNA表达,抑制细胞迁移和侵袭能力。  相似文献   

6.
背景:受体相互作用蛋白140基因敲除小鼠可通过增加线粒体生物功能、脂肪酸氧化、氧化磷酸化等代谢途径来抵抗高脂饮食诱导的肥胖。 目的:构建高脂饮食致肥胖模型小鼠,观察脂肪组织受体相互作用蛋白140 mRNA表达水平变化及胰岛素抵抗的关系。 方法:将C57BL/6J雄性小鼠随机分为对照组和高脂饮食组,分别喂养14周后,测量2组小鼠体质量,选取高脂饮食组中体质量大于对照组小鼠平均体质量20%的小鼠作为肥胖组小鼠。 结果与结论:高脂饮食组小鼠中有12只符合标准计入肥胖组。肥胖组小鼠三酰甘油、总胆固醇、空腹血糖、空腹胰岛素水平和胰岛素抵抗指数均明显高于对照组(P < 0.05或P < 0.01);肥胖组小鼠脂肪组织中受体相互作用蛋白140 mRNA的表达高于对照组(P < 0.05);且小鼠脂肪组织受体相互作用蛋白140 mRNA表达水平与三酰甘油水平、胰岛素抵抗指数呈正相关(r=0.526,P < 0.05;r=0.465,P < 0.05),而与总胆固醇、空腹血糖、空腹胰岛素水平无相关性(P > 0.05)。 中国组织工程研究杂志出版内容重点:肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接:  相似文献   

7.
背景:有研究表明胰岛素样生长因子Ⅰ降低是骨丢失的早期标志。 目的:测定大鼠牙槽骨组织中胰岛素样生长因子Ⅰ的活性,探讨丹参素防治牙槽骨骨质疏松症的可能机制。 方法:SD大鼠随机分为对照组、去卵巢组和丹参素组,后两组行双侧卵巢切除,对照组和去卵巢组用蒸馏水灌胃,丹参素组用丹参素12.5 mg/(kg•d)灌胃。给药90 d后取大鼠牙槽骨,检测牙槽骨量、牙槽骨组织中胰岛素样生长因子Ⅰ活性。 结果与结论:与对照组相比,去卵巢组骨小梁面积百分数减少33.88%(P < 0.05),骨小梁分离度增加43.58%(P < 0.05),牙槽骨骨量明显减少,牙槽骨组织中胰岛素样生长因子Ⅰ表达变少、变弱(P < 0.05)。与去卵巢组相比,丹参素组骨小梁面积百分数增加了45.45%(P < 0.05),牙槽骨骨量明显增多,牙槽骨组织中胰岛素样生长因子Ⅰ表达增强(P< 0.05)。结果证实,丹参素能促进牙槽骨组织胰岛素样生长因子Ⅰ活性,防止去卵巢大鼠牙槽骨的丢失。  相似文献   

8.
目的: 探讨人胰岛素样生长因子1(hIGF-1)基因转染对大鼠骨骼肌成肌细胞体外缺血再灌注损伤的影响及机制。方法: 分别用pLghIGF-1SN质粒(IGF组)和对照质粒pLgGFPSN(GFP 组)转染大鼠成肌细胞。未转染的成肌细胞(control组)作为细胞对照。转染后用免疫细胞化学、RT-PCR及ELISA检测基因表达。转染后3~14 d检测各组细胞的扩增率。转染的细胞接受缺血再灌注损伤后7 d,TUNEL法检测各组细胞的凋亡百分数,RT-PCR 检测各组细胞的bax和bcl-2 mRNA的表达,Western blotting检测各组细胞caspase-3的表达。结果: 基因转染后免疫细胞化学和RT-PCR 检测发现IGF组细胞有hIGF-1表达,GFP组和control组细胞未见hIGF-1表达;IGF组细胞上清中可检测到hIGF-1的蛋白表达,control组和GFP组细胞上清中未检测到hIGF-1蛋白表达。转染后14 d,IGF组细胞的扩增率显著大于control组和GFP组(P< 0.05);细胞经缺血再灌注损伤后,TUNEL染色检测结果显示:与GFP组相比,IGF组细胞的凋亡百分比显著降低(P< 0.05);RT-PCR 检测结果显示:与GFP组相比,IGF组细胞的bax mRNA表达显著降低,bcl-2 mRNA的表达显著增加(P< 0.05);Western blotting检测结果显示:与GFP组相比,IGF组细胞caspase-3蛋白表达显著降低。结论: IGF-1基因转染可增加成肌细胞的抗凋亡能力,其机制可能和降低Bax和caspase-3表达,增加Bcl-2的表达有关。  相似文献   

9.
目的 通过对大鼠肺组织中Toll样受体4(TLR-4)和转化生长因子β1 (TGF-β1)表达影响的研究及对大鼠肺组织病理形态的观察,评价青蒿琥酯对哮喘大鼠的药理作用.方法 清洁级SD雄性大鼠32只,随机分为对照组、哮喘组、地塞米松组和青蒿琥酯组,采用激发和雾化吸入的方法建立哮喘模型.观察各组大鼠肺组织病理改变;取相关...  相似文献   

10.
背景:多种肿瘤中胰岛素样生长因子1受体及其配体表达异常,且胰岛素样生长因子1是多种细胞的有丝分裂原和抗细胞凋亡的因子,控制多种细胞的增殖、分化和凋亡的进程。 目的:观察胰岛素样生长因子1及胰岛素样生长因子1受体在病理性瘢痕中的表达。 方法:收集中山大学附属第一医院烧伤外科收治患者增生性瘢痕、瘢痕疙瘩及其正常皮肤等手术切除标本,荧光定量实时PCR检测不同组织中胰岛素样生长因子1及其受体mRNA的表达水平。 结果与结论:瘢痕疙瘩及增生性瘢痕中胰岛素样生长因子1 mRNA表达水平均高于正常皮肤(P < 0.05),且在瘢痕疙瘩及增生性瘢痕组织中胰岛素样生长因子1表达水平差异无显著性意义(P > 0.05),胰岛素样生长因子1受体在增生性瘢痕表达水平与正常皮肤接近(P > 0.05);而瘢痕疙瘩中胰岛素样生长因子1受体明显高于瘢痕周围正常皮肤(P < 0.05)。说明胰岛素样生长因子1及其受体在病理性瘢痕的形成过程中起重要作用。  相似文献   

11.
Androgens are known to regulate gene expression in the renal proximal tubule. Whether the distal parts of the nephron, in particular the cortical collecting duct (CCD), where sodium reabsorption is controlled tightly by aldosterone, are also targets for these hormones is unknown. Real-time PCR on rat isolated renal tubules showed that androgen receptor mRNA is not only, as expected, expressed in the proximal tubule, but also in the CCD. We examined the effects of adrenalectomy (ADX) plus castration and in-vivo administration of the active metabolite of testosterone, dihydrotestosterone (DHT), on the intrarenal expression of N-myc downstream regulated gene 2 (NDRG2), an early aldosterone-induced gene located specifically in the CCD. NDRG2 belongs to a newly identified family of differentiation-related genes; although the function of these genes remains elusive, regulation of NDRG1 by androgens has been suggested. Castration plus ADX increased NDRG2 expression (RNase protection assay) significantly in the whole kidney, and a single i.p. injection of DHT caused a significant decrease in NDRG2 expression 4 h afterwards (up to 24 h). Furthermore, real-time PCR on microdissected tubules revealed that the decrease in NDRG2 expression caused by DHT is restricted to the CCD. Thus, aldosterone and androgens have opposite effects on NDRG2 expression in the renal CCD. These results are the first demonstration of androgen-dependent gene regulation in the rat renal CCD.  相似文献   

12.
A double-blind, randomized, placebo-controlled study was conducted in 46 postmenopausal women with established osteoporosis in order to assess the long-term effects of nandrolone decanoate on the bone mineral density (BMD) of the lumbar vertebrae and of the distal third of the radius and on the biochemical markers of bone turnover. The patients received intramuscular injections of placebo or 50 mg nandrolone decanoate every 3 weeks for 18 months. Thirty-two of the initial 46 patients completed 1 year of study and 25 completed the whole study period of 18 months. Overall, vertebral BMD increased by 2.9% in the nandrolone decanoate group and fell by 2.3% in the placebo group. Radial BMD showed a slight but transient improvement, with a subsequent return to basal levels in the nandrolone decanoate group, whereas there was a progressive decrease in the placebo group. Patients treated with nandrolone decanoate also complained less of bone pain. Urinary hydroxyproline decreased significantly in treated patients, whereas osteocalcin tended to increase, but the change was not significant. HDL cholesterol concentrations decreased only slightly and haemoglobin increased significantly in the nandrolone decanoate group. Two patients treated with nandrolone decanoate withdrew from the study because of hirsutism and hoarseness. The results indicate that nandrolone decanoate exerts positive effects on vertebral BMD and on bone pain in patients with established postmenopausal osteoporosis.  相似文献   

13.
本文以~(125)I-oPRL为放射催标记配体,利用受体放射分析法,对哺乳期大鼠肝细胞泌乳素受体进行了研究。结果表明。大鼠肝细胞泌乳素受体与泌乳素的结合具有高度特异性和可饱和性,而且受反应时间和pH值大小的影响;这种结合并非简单的双分子反应,大鼠肝细胞泌乳素受体很可能存在两种亲和力高低不同的结合位点(Kd_1=3.20×10~(10)M,Kd_2=1.26×10~(-8)M)或负协同调节。本研究为将来深入开展泌乳素对肝脏机能调节机制的探讨打下了基础。  相似文献   

14.
Associated with acts of violence and polydrug use, abuse of anabolic androgenic steroids (AAS) is an increasing problem in society. The aim of the present study was to elucidate whether sub-chronic treatment with the AAS nandrolone decanoate affects dopamine release and dopamine metabolism in the rat nucleus accumbens shell, before and after an amphetamine challenge. Male Sprague–Dawley rats received daily i.m. injections of nandrolone decanoate (15 mg/kg) or vehicle for 14 days. On day 15, the animals were anaesthetized and a microdialysis probe was implanted into the nucleus accumbens shell. Extracellular fluid was collected 1 h before and 3 h after a single amphetamine injection (5 mg/kg). The samples were then analyzed regarding the content of dopamine, and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), using HPLC with electrochemical detection. Two weeks of nandrolone decanoate administration caused a significant decrease of the basal DOPAC and HVA levels, which remained low during the first hour following the amphetamine challenge. Dopamine levels did not differ significantly between groups, neither after the nandrolone pre-treatment nor the amphetamine challenge. In conclusion, these novel findings indicate that AAS alter the metabolism of dopamine in a brain region involved in the development of drug dependence.  相似文献   

15.
血管紧张素Ⅱ受体在大鼠肝星状细胞上的表达   总被引:3,自引:1,他引:3       下载免费PDF全文
目的: 了解血管紧张素Ⅱ的Ia亚型受体(AT1a)在大鼠肝星状细胞中的表达情况。方法: 大鼠肝脏经链霉蛋白酶和Ⅳ型胶原酶循环灌注后, 以11% Nycodenz密度梯度离心, 分离获得肝星状细胞。提取肝星状细胞的总核糖核苷酸(RNA), 以逆转录-聚合酶链式反应(RT-PCR)技术和PCR产物测序方法检测AT1a表达。结果: 采用RT-PCR技术检测到大鼠肝星状细胞有AT1a mRNA表达, 且PCR产物的测序结果与GenBank上AT1a cDNA序列有94%的一致性。结论: AT1a mRNA在大鼠肝星状细胞上表达, 从而又为探索肝纤维化的发生机制提供了有力的依据。  相似文献   

16.
目的 探讨脂代谢相关基因在低密度脂蛋白受体(LDLR)基因缺失(LDLR-/-)小鼠肝脏中的表达特征及其与血脂紊乱和动脉粥样硬化早期病变的关系.方法 应用RT-PCR技术分析14、30、60和90天龄LDLR-/-与野生型(WT)小鼠靶基因表达差异,并进行血生化及主动脉形态学检测.结果 与同龄WT小鼠相比,LDLR-/-小鼠肝脏中载脂蛋白AⅣ、脂肪酸转运酶和肉碱棕榈酰转移酶Ⅰ的mRNA水平在14天龄时即显著下调(P<0.05);30天龄时载脂蛋白A Ⅰ显著上调,载脂蛋白F则显著下调(P<0.05);60天龄时肝X受体α显著升高(P<0.05),酰基辅酶A氧化酶1在90天龄时显著下调(P<0.05);载脂蛋白A Ⅴ、载脂蛋白E、过氧化物增殖物激活受体α和血管生成素样蛋白3差异无统计学意义(P>0.05).血清总胆固醇、甘油三酯和低密度脂蛋白C含量从14天龄起均显著高于同龄WT小鼠(均P<0.05),并随年龄增长持续升高.结论 上述脂代谢相关基因在幼龄小鼠即发生表达水平的改变,与血脂紊乱及主动脉病变发生过程呈正相关,说明其可能共同参与幼龄小鼠的脂质代谢紊乱,进而影响动脉内皮细胞功能改变乃至动脉粥样硬化早期病变的发生.  相似文献   

17.
Dexamethasone treatment in the rat produced depolarization of extensor digitorum longus (EDL) muscle fibers but not soleus (SOL) fibers studies in vitro at 23° C. The depolarization of EDL fibers was most prominent after 1 day of treatment (treated–77.5±1.1 mV, control–87.2±0.8 mV; mean±S.E.), and was associated with elevation of the action potential threshold and reduction of the action potential overshoot. In vivo, or in vitro in chloride-free solution, the resting potential and action potential threshold and overshoot of EDL fibers from glucocorticoid-treated and control rats were similar. Sodium currents were studied with a patch voltage clamp. Glucocorticoid treatment did not alter the voltage dependence of sodium channel activation or inactivation currents at about –29 mV and half-maximal inward currented at about –50 mV. Sodium channels were half inactivated at about –71 mV. Glucocorticoid treatment did not alter the sarcolemmal resistance or capacitance. We conclude that glucocorticoid treatment does not produce muscle weakness or atrophy by altering the excitability of muscle fibers.  相似文献   

18.
目的:阐明糖皮质激素受体(GR)减少对严重烫伤大鼠体内几种炎闰介质水平的影响。方法:以RU38486阻断严重烫伤大鼠体内的GR,观察其血浆磷脂酶A2(PLA2)活性、肿瘤坏在子α(TNFα)和丙二醛(MDA)呈以及脏器组织匀浆中PLA2活性和MDA含量变化。结果:烫伤后8h,大鼠血浆及肺、肾组织匀浆中PLA2活性,MDA和TNF含量均明显高于假处理对照组;烫伤复合GR阻断组以上效应更显著。结论:烫  相似文献   

19.
The kinetics of myosin light chain (LC20) phosphorylation has been studied during in vitro contraction and relaxation of rat uteri. Phosphorylation preceded contraction and continued during tetanus induced by KCl; the degree of phosphorylation was proportional to the percentage of contraction. On the other hand, during relaxation induced by isoproterenol, the level of phosphorylation did not change in the seconds following relaxation. A rapid change in cAMP did not appear to trigger a rapid change in LC20 phosphorylation.In cyclic rats, progesterone decreased the extent of LC20 phosphorylation: 50%–60% of the LC20 was phosphorylated in untreated animals or estrogen treated animals. This value fell to 30% after progesterone treatment of cyclic rats. In ovariectomized rats, steroid hormones did not affect the phosphorylation reaction.Under the same conditions, the level of cAMP-dependent protein kinases did not change during the cycle, or after estradiol-treatment, but in cyclic rats it doubled after progesterone treatment. Hence, the decrease in the level of LC20 phosphorylation observed in cyclic rats trated by progesterone could be due to a decrease in myosin light chain kinase (MLCK) activity, resulting from a higher proportion of the phosphorylated form of this enzyme. The concomitant increase in the proportion of activatable cAMP-dependent protein kinases could favor the maintenance of a higher level of phosphorylated MLCK for longer periods of time.  相似文献   

20.
A 14 d ovarian primordium was transplanted with a fetal testis (13–18 d and 21 d of gestation) or a neonatal testis (15, 20, 30 and 45 d after birth) into the renal subcapsular position of an adult male rat. Two weeks after transplantation, transplants were examined as to the degree of ovarian and testicular differentiation. In the combination of a 14 d ovary and a 13 d testis, there were 3 types of result: either the ovary or the testis alone developed or both gonads developed well. Ovaries transplanted in union with 15–18 d testes did not develop, although the testes developed normally. Some ovaries in union with 21 d testes developed normally. In combination with infantile testes, the incidence of developed ovaries increased as the age of testes advanced. These results suggest that the 13 d fetal testes begin to suppress the development of cotransplanted 14 d ovaries, that 14–18 d fetal testes maintain such suppressive effects and that this effect gradually diminishes in infantile testes as they progress toward 45 d after birth.  相似文献   

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