穴位埋线对血管性痴呆大鼠学习记忆及海马胆碱乙酰转移酶表达的影响

目的探讨穴位埋线对血管性痴呆（VD）大鼠学习记忆的影响及其机制。方法改良Pulsinelli′s 4血管阻断法建立VD大鼠模型;造模后给予穴位埋线治疗;采用Morris水迷宫检测学习记忆能力及免疫组化检测胆碱乙酰转移酶（ChAT）表达。结果穴位埋线VD大鼠学习记忆能力提高;海马齿状回ChAT表达增强。结论穴位埋线可提高VD大鼠学习记忆能力,可能与它增强海马ChAT表达、保护胆碱能神经元有关。     

健脑安对血管性痴呆模型大鼠海马胆碱乙酰转移酶和突触素表达的影响

目的观察健脑安对血管性疾呆(VD)大鼠海马胆碱乙酰转移酶(ChAT)和突触素(Syn)表达的影响。方法健脑安口服给药治疗VD大鼠1月后采用免疫组化技术观测大鼠海马ChAT和Syn表达变化,与都可喜(Duxil)对照。结果①各组大鼠海马ChAT和Syn阳性表达面积比较如下,健脑安组(2 980±786.53)/(2 948.0±811.92)μm2和都可喜组(3 116.6±808.25)/(3 086.5±862.48)μm2均明显高于模型组(1 004±464.4)/(1 704±671.74)μm2)P值均<0.01)。②ChAT免疫组化染色:健脑安组和都可喜组大鼠海马ChAT阳性神经细胞排列较规则,胞浆ChAT阳性染色较明显,可见阳性染色神经纤维,较密集。③Syn免疫组化染色:健脑安组和都可喜组大鼠海马神经细胞周围Syn阳性颗粒密集、染色深,可见少量胶质细胞。健脑安组和都可喜组比较未见有明显差异。结论健脑安具有显著增加VD大鼠海马ChAT和Syn表达的作用,这可能是其改善痴呆认知和记忆障碍的作用机制。     

促红细胞生成素对血管性痴呆大鼠海马CA1区胆碱乙酰转移酶的影响

目的探讨促红细胞生成素(EPO)对血管性痴呆(VaD)大鼠海马CA1区胆碱乙酰转移酶(ChAT)的影响。方法将经行为学筛选合格的Wistar大鼠随机分为假手术组(Sham组)、VaD组、EPO侧脑室注射+VaD组(E1组)和EPO腹部皮下注射+VaD组(E2组),采用永久性结扎双侧颈总动脉的方法建立VaD模型。通过免疫组织化学和RT-PCR方法检测VaD大鼠海马CA1区ChAT蛋白含量以及ChAT mRNA表达水平的变化。结果 EPO能明显改善VaD大鼠认知功能障碍,上调海马CA1区ChAT表达。结论 EPO可能通过增加VaD大鼠海马区ChAT表达改善其认知功能障碍。     

人参皂苷Rg1对痴呆模型大鼠行为学及酪氨酸蛋白激酶A表达的影响

目的探讨人参皂苷Rg1对痴呆模型大鼠学习记忆能力的影响及其对酪氨酸蛋白激酶A（TrkA）阳性细胞的保护作用。方法采用切断成年Wistar大鼠左侧穹窿海马伞（FF）的方法，建立隔-海马胆碱能系统损害的痴呆模型。分为模型组、治疗组和假手术对照组3组。治疗组经腹腔内注射Rg1（5mg／kg），模型组和假手术对照组给予生理盐水。利用Morris水迷宫测定其学习记忆能力，利用免疫组化及图像分析测定大鼠内侧隔核（MS）和斜角带垂直支（VDB）TrkA阳性细胞数及OD值。结果治疗组大鼠的学习记忆成绩优于模型组（P〈0．05），其MS和VDB的TrkA阳性细胞数及OD值与模型组相比也有改善（P〈0．05）。结论人参皂苷Rg1对中枢胆碱能系统有保护作用，能改善学习记忆能力。     

痴呆大鼠模型行为学、脑内胆碱乙酰转移酶及突触素的改变

目的　观察Meynert核损害对大鼠脑内胆碱乙酰转移酶 (ChAT)和突触素 (p38)的影响。 方法　Ibotenicacid定位损伤大鼠脑建立痴呆模型 ,利用水迷宫和跳台观察其行为学改变 ,利用原位杂交、免疫组化及图像分析测定大鼠脑内ChAT和 p38的表达。 结果　胆碱能损害组大鼠的学习记忆能力低于正常对照组和假手术组 ,其脑内ChAT和p38的表达也明显下降。结论　保护中枢胆碱能系统和增加p38水平有助于改善认知记忆能力     

胰岛素样生长因子-1研究进展

胰岛素样生长因子 1(IGF 1)是一类促进细胞生长、具有胰岛素样代谢效应的因子。IGF 1受营养状态、激素、遗传等多因素的调节 ,在心血管疾病、内分泌代谢病及肿瘤等的病理生理过程中发挥重要作用。研究和利用这一因子 ,解决与之密切相关的多种疾病 ,将为临床医学提供新的思路     

卒中时胰岛素样生长因子-1的表达和作用

胰岛素样生长因子 1(IGF 1)是一种重要的神经生长因子 ,对神经组织的生长、发育和分化具有重要的促进作用 ,对各种原因引起的脑损伤具有营养和保护作用。卒中时 ,IGF 1在脑组织中的表达和分布发生明显变化 ,显示其参与了卒中的病理生理学过程。深入研究IGF 1与卒中的关系 ,探索其在卒中中的作用和机制 ,有可能为卒中的治疗提供一条新途径。     

倍美力对去卵巢痴呆模型大鼠行为学及不同脑区胆碱乙酰转移酶的干预作用

目的 观察去卵巢痴呆大鼠行为学及额叶皮质、基底前脑、海马CA1区胆碱乙酰转移酶(ChAT)的变化及倍美力对其影响,探讨倍美力的脑保护机制.方法 采用穹窿海马伞切除术及双侧卵巢切除制备痴呆及雌激素缺乏复合模型鼠,采用Morris水迷宫观察其行为学变化,利用RT-PCR法观察大鼠额叶皮质、基底前脑、海马CA1区ChAT mRNA的变化.结果 倍美力干预组大鼠学习、记忆能力增强,额叶皮质、基底前脑、海马CA1区ChAT mRNA表达增加(均P＜0.01).结论 倍美力可通过增加额叶皮质、基底前脑、海马CA1区ChAT mRNA表达,改善模型鼠学习及记忆能力.     

神经保护肽慢病毒对老年性痴呆模型大鼠行为学及海马胆碱乙酰转移酶mRNA表达的影响

目的观察神经保护肽慢病毒（rLent／NT4-NAP）对老年性痴呆模型大鼠行为学及海马胆碱乙酰转移酶（ChAT）原位杂交的影响，进一步研究神经保护肽（NAP）对老年性痴呆疾病的治疗作用。方法建立β-淀粉样蛋白（Aβ）大鼠海马注射联用转移因子β1（TGFβ1）脑内注射改良的老年性痴呆大鼠模型。实验分成对照组，假手术组，痴呆组，rLent／NT4-NAP组，空病毒组。空病毒组和rLent／NT4．NAP组通过滴鼻给药方式给予。应用水迷宫试验观察各组大鼠行为学的改变，采用原位杂交技术观测各组大鼠海马神经元胆碱乙酰转移酶（ChAT）mRNA的表达变化。结果各组大鼠水迷宫的学习和记忆成绩比较，rLent／NT4-NAP组优于痴呆组（P〈0．05）；对照组，假手术组，NAP组，空病毒组无显著差别。rLent／NT4-NAP组海马ChATmRNA表达也明显增高。各组海马ChATmRNA阳性神经元面密度之比较，痴呆组ChATmRNA阳性神经元面密度值（0．0698&#177;0．0182），低于对照组（0．12170&#177;0．0165），假手术组（0．1130&#177;0．0154）及rLent／NT4-NAP组（0．1083&#177;0．01718），空病毒组（0．1193&#177;0．01118）（P〈0．05），对照组，假手术组，rLent／NT4-NAP组，空病毒组间无明显差别。结论NAP改善老年性痴呆模型大鼠记忆成绩与其恢复大鼠海马低水平的ChATmRNA表达有关。     

孕烯醇酮对老年大鼠记忆相关脑区胆碱乙酰转移酶表达的影响

目的观察孕烯醇酮对老年大鼠记忆相关脑区胆碱乙酰转移酶(ChAT)表达的影响。方法雄性老年大鼠40只,随机分为空白组、溶剂组、小剂量孕烯醇酮组、大剂量孕烯醇酮组,每组10只。隔日腹腔注射1个月,通过免疫组织化学技术分别检测各组大鼠额叶、颞叶、海马皮质区ChAT表达情况。结果与空白组比较,大剂量孕烯醇酮组大鼠额叶、颞叶、海马皮质区ChAT免疫阳性细胞明显增加,差异有统计学意义(P<0.05);而溶剂组和小剂量孕烯醇酮组ChAT阳性细胞数无明显增加,差异无统计学意义(P>0.05)。结论大剂量孕烯醇酮可以显著改善老年大鼠胆碱能系统活性。     

老年颈动脉粥样斑块与胰岛素样生长因子-1及血脂的相关性研究

目的探讨胰岛素样生长因子1(IGF1)对老年颈动脉斑块(CAP)的影响及其在脂代谢中的作用。方法检测48例经颅多普勒超声确诊的老年CAP患者的血清IGF1水平和血脂指标,并与40例无CAP的老年人对照,并将两组的数据进行相关性分析。结果老年CAP组血清IGF1水平明显低于对照组(P<0.05);而TC、TG、LDL水平均较对照组高(P<0.01);HDL水平无显著差异。斑块组TC、TG、LDL均与IGF1呈负相关;HDL与IGF1无相关性。结论脂代谢紊乱是动脉粥样斑块形成的主要危险因素,IGF1作为一种重要的循环内分泌多肽,参与CAP的形成及脂代谢的调节。     

Caloric restriction promotes the reproductive capacity of female rats via modulating the level of insulin-like growth factor-1 (IGF-1)

The insulin-like growth factor-1 (IGF-1) plays an important role in the regulation of reproductive function. In the present study, we examined the effects of caloric restriction (CR) on the reproductive lifespan in rats and investigated the potential role of IGF-1. After 10 weeks of treatment, we determined the distribution of the ovarian follicles at various stages and measured the plasma level of IGF-1, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrogen (ESG). Our results show that IGF-1 level was decreased after CR and correlated with the decrease in the levels of LH, FSH and ESG. Moreover, a higher percentage of primordial follicles and surviving follicles was observed in CR rats than in control rats (P < 0.05). Immunohistochemical analysis showed that IGF-1 was extensively expressed in the cytoplasm of granulosa cells in the surviving follicles at different stages but not in the atretic follicles. Taken together, these results suggest that caloric restriction promotes the reproductive capacity of female rats via modulating the level of IGF-1, which then regulate pituitary gonadotrope cells to reduce the release of LH, FSH and ESG, and modulate follicular development.     

Intracerebroventricular insulin-like growth factor-1 decreases feeding in diabetic rats

Insulin-like growth factor-1 (IGF-1) is a hormone that is important in the regulation of growth processes and additionally has been demonstrated to modulate metabolic and autonomic responses. Some of its effects are mediated by the central nervous system (CNS), and there are IGF-1 receptors dispersed throughout the CNS. Both IGF-1 and insulin alter peripheral metabolic and autonomic nervous activity by a central mechanism, and the well-defined role of insulin in the regulation of feeding, especially in diabetes, led us to investigate the effect of chronic central administration of IGf-1 on metabolic and feeding parameters in normal and diabetic rats. Normal and diabetic rats with intracere-broventricular cannulas were given IGF-1, insulin (0.5 nmol/animal), or artificial cerebrospinal fluid via cannula twice daily for 4 d. Blood samples were collected on d 2 and 4, and the body weights and food intake were recorded daily. IGF-1 administered intracere-breventricularly did not alter plasma glucose, insulin, body weight, or food intake in normal rats. However, in diabetic animals, IGF-1 decreased food intake but did not alter blood glucose or plasma insulin. In correlated studies, intracerebroventricular insulin decreased food intake in both normal and diabetic animals. From these studies, we conclude that IGF-1 may act centrally to decrease food intake in the hyperphagic diabetic animals but not in normal animals. This suggests that diabetic animals have an increased sensitivity to CNS IGF-1.     

胰岛素样生长因子-Ⅰ在哮喘发病中的作用

胰岛素样生长因子-Ⅰ（insulin-like growth factor-1,IGF-Ⅰ）是一种与胰岛素有高度同源性的具有多功能的生长因子。它能够促进气道中成纤维细胞等问质细胞及炎症细胞的增殖并抑制其凋亡。同时,还可以通过完全依赖Rho激酶的途径,导致人类支气管平滑肌细胞的慢性持续收缩引起气道狭窄。目前认为IGF-Ⅰ在哮喘发病的多个环节中发挥作用,本文就其与哮喘发病的关系进行综述。     

胰岛素样生长因子-1在高脂血症发病中的意义

目的　探讨胰岛素样生长因子 - 1(IGF - 1)对脂代谢的影响及其在高脂血症发病中的作用。方法　使用Westerndotblot杂交 ,检测了不同临床类型高脂血症患者的血清IGF - 1水平 ,并与各项血脂指标进行了相关性分析。结果　单纯高胆固醇血症 (Ⅱa型 )及单纯高甘油三酯血症 (Ⅳ型 )患者 ,其血清IGF - 1水平均明显低于健康对照组 (P <0 0 1) ,而混合型高脂血症 (Ⅱb型 )患者则与对照组没有明显差异 (P >0 0 5 ) ;所有受试对象 ,包括健康对照及高脂血症患者 ,分别考察年龄、TC、TG、HDL、LDL、ApoA、ApoB及LDL/HDL等因素与血清IGF- 1水平的相关关系 ,发现TC、TG、LDL、ApoA及LDL/HDL均与IGF - 1呈负相关。 结果　IGF - 1作为一种重要的循环内分泌多肽 ,参与脂代谢的调节。研究为阐明高脂血症的发生机制提供了一条新的线索。     

非霍奇金淋巴瘤患者血清胰岛素样生长因子-1及其结合蛋白-3表达水平的初步观察

目的:探讨非霍奇金淋巴瘤(NHL)患者血清胰岛素样生长因子-1(IGF-1)及其结合蛋白-3(IGFBP-3)表达水平及其临床意义.方法:选择28例诊断初发NHL患者(淋巴瘤组)及28例健康志愿者(对照组),化学发光法测定血清IGF-1及IGFBP-3水平并计算IGF- 1/IGFBP-3值,分析组间的差异.结果:血清IGF-1及IGFBP-3水平淋巴瘤组显著低于正常对照组(均P＜0.01);IGF-1/IGFBP-3淋巴瘤组与正常对照组差异无统计学意义(P＞0.05);不同亚型的淋巴瘤组的血清IGF-1、IGFBP-3水平及IGF-1/IGFBP-3比值的差异均未达到统计学意义(P＞0.05).结论:N HL患者血清IGF-I及IGFBP-3水平明显降低,可能与NHL相关.IGF-1/IGFBP-3比值与NHL无明显相关性,IGF-1及IGFBP-3水平与NHL的分型无明显相关.     

Different binding and degradation of proinsulin,insulin and insulin-like growth factor-1 (IGF-1) in cultured renal proximal tubular cells

Recent studies have reported that elevated proinsulin levels are indicative of an increased cardiovascular risk. Renal proximal tubular cells represent a major site for the metabolism of insulin-like hormones after glomerular filtration into the tubular lumen. To determine the binding and degradation of proinsulin in comparison with insulin and insulin-like growth factor-1 (IGF-1), we have used a rabbit proximal tubular cell line (PT-1). As confirmed by electron microscopy, PT-1 cells exhibit bipolar differentiation, demonstrating apical microvilli and invaginations of the basolateral membrane. To allow selective incubation of both compartments, cells were grown on filter membranes. Performing equilibrium binding assays with¹²⁵I-labelled hormones, severalfold higher binding was found at the apical than at the basolateral cell membrane, with the capacity range IGF-1>insulin>proinsulin. Half-maximal displacement of¹²⁵I-labelled insulin and IGF-1 was observed at 0.6 and 2 nM, respectively, while crossover binding to the alternate receptor occurred with a 10- to 100-fold lower affinity. Half-maximal displacement of¹²⁵I-proinsulin binding was obtained at approx. 8 nM proinsulin and insulin, whereas IGF-1 was 10-fold less potent. The relative degradation of specifically bound tracer was lowest for proinsulin (apical: 10%, basolateral: 13%). IGF-1 was degraded by 20% at the apical cell membrane, and up to 78% at the basolateral membrane. In contrast, almost the total amount of insulin bound was degraded at both membrane sites (apical: 99%, basolateral: 83%). These results suggest separate insulin and IGF-1 receptors, while proinsulin binds with high affinity to a third insulin-like receptor on the apical membrane of PT-1 cells.     

Expression of ovine insulin-like growth factor-1 (IGF-1) stimulates alveolar bud development in mammary glands of transgenic mice

To determine whether murine mammary growth is modulated by local insulin-like growth factor-1 (IGF-1) production, expression of recombinant IGF-1 was directed to the mammary glands of transgenic mice using an ovine prepro IGF-1 cDNA under control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR) promoter. Bioactivity of recombinant IGF-1 in transgenic mouse milk extracts was demonstrated by a concentration-dependent increase in [³H]thymidine incorporation in clonal bovine mammary epithelial cells (MAC-T) compared with control mouse milk extracts; moreover, addition of excess recombinant human insulin-like growth factor binding protein-3 (rhIGFBP-3) abolished the increase in [³H]thymidine incorporation attributed to recombinant IGF-1 in transgenic mouse milk. Recombinant IGF-1 was produced in mammary tissue of virgin and pregnant transgenic mice, and secreted into milk of lactating mice. However, recombinant IGF-1 was not detected in serum from transgenic mice; and ligand blot analysis of serum insulin-like growth factor binding proteins (IGFBPs) indicated no differences owing to transgene presence. In peripubertal virgin mice at 49 d of age, the frequency of appearance of mammary alveolar buds was significantly higher in MMTV-IGF-1 than in CD-1 mice, and was unaffected by ovariectomy or estradiol treatment. In conclusion, mammary synthesis of recombinant IGF-1 enhances the rate of development of alveolar buds in mammary glands of virgin transgenic mice.     

宫内发育迟缓与胰岛素样生长因子及其结合蛋白关系的研究

为探讨宫内发育迟缓（IUGR）的发生机制,检测了86例新生儿脐血胰岛素样生长因子－1（IGF－1）、胰岛素样生长因子结合蛋白－3（IGFBP－3）水平,并分析上述指标变化与胎儿期生长的关系。将86例新生儿分为两组,IUGR（即小于胎龄儿）组22例,适于胎龄儿（AGA）组64例,采用竞争性放射免疫分析法（RIA）测定两组脐血IGF－1水平,非竞争性免疫放射分析法（IRMA）测定IGFBP－3水平。结果显示,与AGA组相比,IUGR组脐血IGF－1和IGFBP－3水平显著降低（P＜0．001）;IGF－1水平随胎龄及出生体重增加而增加（P＜0．01）;IGFBP－3水平与胎龄及出生体重呈相关（P＜0．01）;IGF－1与IGFBP－3呈正相关（P＜0．01）。认为IUGR与IGF－1及其结合蛋白密切相关,不论何种原因引起的IUGR,其脐血IGF－1、IGFBP－3水平均低,IGF－1水平下降与IGFBP－3下降相伴随;脐血IGF－1、IGFBP－3水平与胎龄及出生体重呈正相关,随着胎龄的增加和出生体重的增长,IGF－1、IGFBP－3水平不断升高。     

The role of insulin-like growth factor-1 (IGF-1) in growth and reproduction in female brown house snakes (Lamprophis fuliginosus)

Insulin-like growth factor-1 (IGF-1) is a peptide hormone critically involved in the regulation of key life-history traits such as growth and reproduction. Its structure and function are well-characterized among diverse mammal, fish, and bird species; however, little is known regarding the activities of IGF-1 in non-avian reptiles, particularly snakes and lizards. Nevertheless, several unique characteristics of reptiles, such as high metabolic flexibility and remarkable diversity in life-history strategy, suggest that they are of great interest in the study of endocrinological mechanisms underlying the regulation and evolution of life-history traits. Here we test for a relationship between IGF-1 and individual feeding rate, growth rate and reproductive stage in lab-reared female offspring of wild-caught oviparous house snakes, Lamprophis fuliginosus. We confirm a positive correlation between IGF-1 and both feeding and growth rates in sexually immature snakes, similar to that reported in other taxa. We also show a family effect on IGF-1, suggesting that IGF-1 levels may be heritable in these snakes, and serve as an important target of selection to produce divergent life-history strategies. Furthermore, we provide evidence that suggests that IGF-1 may peak rapidly after first mating, and subsequently decline prior to egg-laying, a phenomenon not previously reported in other taxa. These findings suggest that further comparative study of IGF-1 in snakes may reveal both the extent to which IGF-1 function is conserved across major taxonomic groups, as well as novel and intriguing roles for IGF-1 in the regulation of reproductive activities.