Nogo—p4与NgR结合抑制神经干细胞分化为双极形星形胶质细胞的突起生长

目的观察Nogo—p4是否通过与NgR结合的途径对大鼠脊髓来源神经干细胞分化形成双极形星形胶质细胞突起长度产生抑制。方法取4只出生24h内的Wistar大鼠,悬浮培养法培养大鼠脊髓来源的神经干细胞。把神经干细胞分为A、B、C、D四组,A组加入血清,B组加入血清和Nogo—p4,C组神经干细胞经RNA干扰沉默NgR基因后加入血清分化,D组神经干细胞经RNA干扰沉默NgR基因后加入血清和Nogo—p4。分化第7d,GFAP抗体标记星形胶质细胞,使用Image—ProPlus5．0软件测量双极形星形胶质细胞突起长度。结果神经干细胞分化第7d,四组均可形成双极形星形胶质细胞。B组中双极形星形胶质细胞的突起长度明显短于其它各组。A、C、D组中双极形星形胶质细胞的突起长度没有显著差异。结论Nogo—p4经与NgR结合途径显著抑制脊髓来源神经干细胞分化成的双极形星形胶质细胞的突起生长。     

奖励性操作式条件反射任务在大鼠学习记忆研究中的应用

目的将奖励性操作式条件反射方法应用于学习记忆研究。方法首次采用奖励性操作式条件反射方法,设置单次操作训练、连续多次操作训练、信号辨识与消退四种检测模式,研究Wistar大鼠和SHR大鼠学习记忆能力。结果奖赏训练中,SHR组鼻触次数显著增多（vs.Wistar＆Donepezil,P〈0.05）;单次操作训练中,三组动物对操作反应的获得无显著差异;连续多次操作学习任务中,SHR组错误操作次数增多（vs.Wistar,P〈0.05）,奖赏获得次数减少（vs.Donepezil,P〈0.001）,反应准确率显著降低（vs.Wistar＆Donepezil,P〈0.05）;信号辨识任务中SHR组错误反应次数显著增多（vs.Wistar＆Donepezil,P〈0.05）,而反应准确率降低,组间差异有显著性（vs.Wistar＆Donepezil,P〈0.05）;消退实验中,三组动物差异无显著性。神经递质检测发现,SHR组大鼠谷氨酸[（1.0639±0.07086）mg/g]、乙酰胆碱[（2.7760±0.2609）μg/g]与五羟色胺[（1.2200±0.1137）μg/g]含量均显著低于Wistar组大鼠（P〈0.05）,多奈哌齐组大鼠乙酰胆碱含量显著增加[（3.9344±0.2747）μg/g]（vs.Wistar,P〈0.05;vs.SHR,P〈0.001）。结论奖励性操作式条件反射方法可作为一种正性增强条件反射检测新方法应用于大鼠学习记忆研究。     

Fe bioavailability from Fe-enriched yeast biomass in growing rats

The Fe content in animal feeds is highly variable. The availability of Fe in feeds varies with the feed and the form in which Fe is present. The present study reports the effect of the addition of different concentrations of Fe from yeast biomass on Fe bioavailability and Fe level in rat liver, compared with a diet containing Fe-sulphate (Fe-sulphate) addition (control) and with a diet without any addition of Fe. Male Wistar rats were fed ad libitum for 10 days a diet with different levels of Fe-enriched yeast biomass (20, 35 and 50 mg of Fe), or Fe-sulphate diet (50 mg of Fe) or without Fe addition. Faeces and urine were collected for Fe analyses during the last 5 days of the test period. The results clearly showed a highly significant (P < 0.001) better bioavailability of Fe from Fe-enriched yeast biomass, independent of the level of Fe in the diet. This was on average 36% higher than the availability of Fe from the Fe-sulphate-enriched diet. Liver Fe storage depended on the level of Fe in the diet from yeast biomass. A significantly lower amount of Fe was found to be incorporated in the liver in the group with an inorganic source of Fe (Fe-sulphate) in the diet.     

9种Na+通道mRNA在5个不同发育阶段大鼠16种组织中表达及变化趋势

电压-门控Na⁺通道由1个可单独发挥作用的α亚单位和2～4个起辅助作用的β亚单位构成,在可兴奋细胞动作电位的产生及传导等过程中起重要作用.采用RT-PCR法对5个不同发育阶段(P1、P9、P40、P80、P120)Wistar大鼠16种不同组织的9种Na⁺通道α亚单位及1种β亚单位的mRNA进行检测发现：同种类型Na⁺通道mRNA在大鼠不同组织中的表达不同,不同类型Na⁺通道mRNA在大鼠同一组织中的表达不同.其中,神经系统和心肌组织中Na⁺通道mRNA的表达最高,随着日龄的增加,Na⁺通道mRNA在不同组织中表达的变化趋势不同.Na⁺通道在全身组织中的广泛分布及随发育周期的不同变化趋势,为离子通道病的研究及治疗提供了理论基础.     

vWF与IL-6预测肾性高血压大鼠经历人工寒潮发生卒中的研究

目的:观察易卒中型肾血管性高血压大鼠(RHRSP)在经历人工寒潮中风前血液中vWF与IL-6含量变化从而预测中风的发生.方法:双肾双夹法制作RHRSP模型,经历人工寒潮并于寒潮前取血,酶联免疫吸附测定(ELISA)法检测vWF与IL-6含量.结果:脑梗塞组寒潮前vWF的表达明显高于非卒中组,脑梗死组和脑出血组寒潮前的IL-6含量明显高于非卒中组.结论:高血压患者血液中IL-6和vWF的含量可能预测经历寒潮时发生脑卒中的情况.     

The cholesterol lowering properties of the complex compound simvastatin with glycyrrhizic acid (simvaglyzin) in experimental models

A molecular complex of simvastatin (SV) and glycyrrhizic acid (GA) (at their ratio of 1 : 4) has been synthesized. The complex named “simvaglyzin” (SVG) was stable in aqueous and aqueous-alcohol solutions at GA concentrations exceeding 0.2 mM. In vitro SVG acted as an uncompetitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA (3-HMG-CoA) reductase (Ki of 94 nM). Appearance of this inhibitory activity is associated with cytochrome P450-dependent conversion of SVG, because the addition of 1 mM metyrapone to the incubation medium fully prevented the inhibition of 3-HMG-CoA reductase. SV and SVG (used at 300 nM concentration) inhibited mevalonate synthesis rate by 39.15±8,27 and 38.85±3,04%, respectively. In vivo SVG showed a dose-dependent cholesterol lowering effect. In rats the cholesterol lowering effect of SVG used at daily doses equivalent to 66 and 100 mg/kg of SV was the same as the effect of SV administered at the daily dose of 200 mg/kg. The decrease in total cholesterol of blood serum was 7% and 9% (p < 0.05) and 8%, respectively. Myotoxicity of these SVG doses estimated by blood serum creatine phosphokinase (CPK) activity was lower than that of SV. In rats treated with SV the activity of CPK increased by 79% (p < 0.01), while in SVG treated rats it decreased by 30% and 36% (p < 0.05). Any increase of the hepatotoxicity markers alanine aminotransferase or aspartate aminotransferase in blood serum was not observed. The data suggest pharmacological synergism attributed to the SV-GA complex formation and increased safety of the resultant complex compared with a parent compound.     

Anti-diabetic Effects of Cesium Aqua (N,N′-ethylene(salicylideneiminato)-5-sulfonato) Oxovanadium (IV) Dihydrate in Streptozotocin-induced Diabetic Rats

The study has been designed to investigate the anti-diabetic effects of cesium aqua (N,N′-ethylene (salicylideneiminato)-5-sulfonato) oxovanadium (IV) dihydrate (VO(salen-SO₃)), an organic vanadium compound, in streptozotocin-induced diabetic rats. VO(salen-SO₃) was orally administrated to diabetic rats at the dose of 0.3 mg/ml through drinking water for 24 days. Blood glucose level was significantly declined, and oral glucose tolerance was improved after VO(salen-SO₃) treatment. Moreover, liver and muscle glycogen concentrations were markedly increased in VO(salen-SO₃)-treated diabetic rats. On the other hand, aspartate amino transferase and blood urea nitrogen in serum were significantly decreased after treatment with VO(salen-SO₃). Take together, these results suggested that VO(salen-SO₃) may be of potential value in the therapy of diabetic symptom and hyperglycemia-induced hepatic and renal dysfunction.     

GDNF prevents TGF-β-induced damage of the plasma membrane in cerebellar granule neurons by suppressing activation of p38-MAPK via the phosphatidylinositol 3-kinase pathway

Transforming growth factor-β (TGF-β) and glial-cell-line-derived neurotrophic factor (GDNF) have been shown to synergize in several paradigms of neuronal survival. We have previously shown that cerebellar granule neurons (CGN) degenerate in low potassium via ERK1/2 (extra-cellular-regulated kinase)-dependent plasma membrane (PM) damage and caspase-3-dependent DNA fragmentation. Here, we have investigated the putative synergistic function of GDNF and TGF-β in CGN degeneration. GDNF alone prevents low-potassium-induced caspase-3 activation and DNA fragmentation but does not affect either low-potassium-induced ERK activation or PM damage. TGF-β alone does not affect low-potassium-induced DNA fragmentation but potentiates low-potassium-induced PM damage. This effect of TGF-β is independent of ERK1/2 activation but dependent on p38-MAPK (mitogen-activated protein kinase) activation. When co-applied with TGF-β, GDNF paradoxically antagonizes TGF-β-induced potentiation of PM damage by inhibiting TGF-β-induced p38-MAPK activation. In addition, PI3K (phosphatidylinositol 3-kinase) inhibitors abolish the GDNF effect. This study thus demonstrates a differential mechanism of action of GDNF and TGF-β on CGN degeneration. GDNF inhibits caspase-3-dependent DNA fragmentation but does not affect ERK-dependent PM damage. However, GDNF can attenuate TGF-β-induced p38-MAPK-dependent PM damage via the PI3K pathway. This work was supported by the Deutsche Forschungsgemeinschaft (STR 616/1–2) and by a fellowship (Young Investigator Award) from the Medical Faculty, University of Heidelberg, Germany to S. Subramaniam.     

Somatostatin-14 influences pituitary–ovarian axis in peripubertal rats

The effects of multiple somatostatin (SRIH-14) administration on the pituitary-ovarian axis were examined in peripubertal rats. Female Wistar rats received subcutaneously, two daily doses of 20 mug SRIH-14 per 100 g body weight (b.w.) for five consecutive days (from the 33rd to the 37th day of life). Follicle-stimulating (FSH), luteinizing (LH) and somatotropic (GH) cells were examined by the peroxidase-anti-peroxidase immunocytochemical method. Changes in cell volumes, volume densities and number per unit area (mm(2)) of FSH-, LH- and GH-immunoreactive cells were evaluated by stereology and morphometry. Serum FSH and LH levels were determined by RIA. Ovaries were analyzed by simple point counting of follicles. The volumes and volume densities of FSH-, LH- and GH-immunoreactive cells were significantly decreased while their numbers per mm(2) remained unchanged. SRIH-14 induced a significant decrease in serum FSH and LH levels. In the ovary, SRIH-14 induced an increase in the number of primordial follicles, followed by a reduction in the number of small healthy growing follicles and absence of preovulatory follicles. The number of atretic follicles was unchanged. We concluded that treatment with SRIH-14 during the peripubertal period markedly inhibited pituitary FSH, LH and GH cells. In the ovary, SRIH-14 acted by inhibiting folliculogenesis without affecting atretic processes.