蓝斑核在帕金森病发病中的病理改变及其作用

目的帕金森病是一种常见的神经变性性疾病,其病理特征为中脑黑质多巴胺能神经元的选择性和进行性变性。而近来的临床资料提示,在帕金森病早期,脑桥蓝斑核的去甲肾上腺素能神经元先于黑质发生病变。实验室研究也发现,蓝斑变性后,黑质多巴胺能神经元的电生理状态、神经递质代谢活动会发生改变,对损伤因素的易感性增高,促进了帕金森病的发病。其原因可能为蓝斑通过调节递质释放、摄取毒物、分泌营养物质等方式影响黑质多巴胺能神经元以及该区域的神经胶质细胞,对多巴胺系统起到保护作用。本文综述了帕金森病临床资料中蓝斑的病理表现、以及基础研究中蓝斑与黑质的关系以及蓝斑对黑质起保护作用的可能机制。本综述应能为深入研究帕金森病的发病机制提供参考。     

Hypertension and Exercise

A sedentary lifestyle may be a risk factor for hypertension, according to the results of both cross sectional and longitudinal studies. However, exercise may reverse the adverse effects of lack of activity. Many controlled studies have shown that exercise lowers systolic/diastolic blood pressure by at least 10/5 mmHg. Exercise not only improves blood pressure, but also attenuates other risk factors for cardiovascular complications. Dynamic isotonic exercise (e.g., walking) is more effective than static isometric exercise(e.g., weight lifting). Milder (e.g., brisk walking for 30–60 minutes/day) rather than moderate to severe exercise (e.g., running) is also recommended because of similar effectiveness and better compliance. The underlying mechanism of action of exercise on blood pressure seems to be multifactorial involving a decrease in pressor factors such as plasma norepinephrine, the serum Na/K ratio, endogenous ouabain-like substance and erythrocyte mean corpuscular volume, as well as an increase in depressor factors such as plasma prostaglandin E, serum taurine and urinary dopamine excretion.     

Postsynaptic αAl-Adrenoceptors in the Hypertensive Rat: Studies on Vascular Reactivity In Vivo and Receptor Binding In Vitro

An increase in vascular responsiveness (increase in diastolic blood pressure) to phenylephrine (PE), noradrenaline (NA) or angiotensin (AII) was seen in pithed SHR when compared with normotensive controls (WKY). This increase in vasoconstrictor effect was not seen with the postsynaptic α₂-adrenoceptor agonists BHT 933 or TL 99. In SHR and DOCA-salt hypertensive rats prazosin was significantly more potent as an antagonist of α₁-receptor mediated vasoconstriction (PE, or the endogenous release of NA by electrical stimulation of the spinal cord), and was also more potent against NA administered by i.v. injection, compared with normotensive controls. The potency of yohimbine against the postsynaptic α₂-receptor mediated pressor responses to TL 99 was not significantly different in SHR or normotensive rats. Although these results indicate an apparent shift in the ratio of postsynaptic α₁/α₂-receptor mediated effects in hypertension in vivo, these effects were not correlated with any changes in α-receptor density (B max) nor affinity (K_D) of the ligands 3H-prazosin or 3H-yohimbine in membranes prepared from SHR. The     

不同通气方式对髋关节置换高血压患者应激反应的影响

背景：髋关节置换患者全麻时,气管插管可造成咽喉和气管感受器的物理刺激,会引起患者的应激反应增强,尤其是高血压患者。Supreme喉罩能够减轻围术期患者心血管应激反应,降低气道并发症。 目的：观察Supreme喉罩和气管插管对高血压患者髋关节置换应激反应的影响。 方法：取2010年1月至2014年9月于江苏省沭阳仁慈医院行人工髋关节置换的患者45例,采用随机数字表法将患者均分为两组,喉罩组23例,气管插管组22例。两组患者均采用相同的麻醉诱导和维持方法,置换过程中连续监测患者的收缩压、舒张压、心率及血氧饱和度,分别记录两组麻醉诱导前(T0)、插管(喉罩)后即刻(T1)、5 min(T2)、15 min(T3)时收缩压、舒张压、血氧饱和度、心率及血糖、血浆肾上腺素、去甲肾上腺素、血清皮质醇、血管紧张素Ⅱ及心钠素水平。 结果与结论：喉罩组患者收缩压与舒张压在T1-T3时间点较T0时明显降低(P < 0.05);心率、血氧饱和度在T0-T3各时间点比较平稳,差异无显著性意义(P > 0.05)。气管插管组患者收缩压、舒张压在T1时较T0时显著升高,收缩压在T2、T3时较T0明显降低,舒张压在T3时较T0显著降低(P < 0.05),心率、血氧饱和度在T1时间点显著升高(P < 0.05)。与T组比较,喉罩组患者收缩压与舒张压在T1-T3时间点显著降低(P < 0.05),心率在T1、T2较T组明显减慢(P < 0.05),血氧饱和度在T1显著高于T组(P < 0.05)。与T0时比较,T1-T3时气管插管组血糖、血浆肾上腺素、去甲肾上腺素浓度和皮质醇含量明显升高,且显著高于喉罩组(P < 0.05)。T1-T3时气管插管组血管紧张素Ⅱ水平较T0时显著增高,且均高于喉罩组。T1-T3时两组心钠素含量明显升高,气管插管组显著高于喉罩组(P < 0.05)。可见喉罩对于这些与应激相关的生化指标的影响较小,这也是其对患者血流动力学影响较小的生理基础。提示与气管插管比较,喉罩可明显减轻高血压患者全麻状态下髋关节置换时的应激反应。中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

l-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) are known to have cardiac noradrenergic hyperactivity due to an impaired nitric oxide (NO)-cGMP pathway. We hypothesized that dietary l-arginine supplementation may correct this autonomic phenotype. Male SHR and Wistar Kyoto rats (WKY) aged 16-18 weeks were given l-arginine (10 g/L in drinking water) for 1 week. Separate control groups received no supplementation. The SHR control had a significantly lower plasma l-arginine than WKY control, but this was increased to a comparable level following l-arginine. Atrial cGMP was lower in the SHR control compared with the WKY control (2.4 ± 0.4 pmol/mg vs 3.9 ± 0.5 pmol/mg, p < 0.05), but increased to 4.1 ± 0.5 pmol/mg protein (n = 8, p < 0.05) with l-arginine. Evoked [³H]norepinephrine release in isolated spontaneously beating right atria from the SHR control (328 ± 19%, n = 19) was 28% higher than the WKY control (256 ± 20%, n = 14, p < 0.05), but was reduced to 258 ± 11% with l-arginine feeding (n = 24, p < 0.01). Soluble guanylyl cyclase (sGC) inhibition caused a greater increase of evoked norepinephrine release in the l-arginine fed SHR compared with the non-fed SHR. l-arginine feeding did not reduce evoked norepinephrine release in the WKY. In-vitro heart rate response to exogenous norepinephrine (0.1-5 μmol/L) was similar between l-arginine fed (n = 13) and non-fed SHR (n = 10), suggesting that l-arginine supplementation worked pre-synaptically. Myocardial tyrosine hydroxylase protein was decreased in SHR following l-arginine supplementation, providing a link to reduced synthesis of norepinephrine. In conclusion, l-arginine supplementation corrects local cardiac noradrenergic hyperactivity in the SHR, probably via increased pre-synaptic substrate availability of NOS-sGC-cGMP pathway and reduced tyrosine hydroxylase levels.     

慢性心理应激对SKOV3荷瘤裸鼠血清NE、IL-10和CA125的影响

目的:探讨心理应激对肿瘤生长及荷瘤裸鼠血清去甲肾上腺素(NE)、白介素-10(IL-10)和糖链抗原125(CA125)含量的影响。方法:随机将裸鼠分为4组:正常生长组(A组),单纯应激组(B组),荷瘤组(C组)及荷瘤应激组(D组),每组6只。于C、D组裸鼠的腋窝皮下注射SKOV3细胞(2×106cells/只),注射前B、D组先行束缚应激7天,接种后再连续应激35天(每天6h),A、C组不予应激,结束后处死全部裸鼠,剥取肿瘤,做病理检查;取血清测NE、IL-10和CA125含量。结果:成功建立人卵巢癌荷瘤裸鼠慢性心理应激模型。心理应激明显增加荷瘤裸鼠的瘤重(P0.05),肿瘤增长率58.46%;各组血清NE、IL-10水平依次为ACD,ABD,差异均有统计学意义(P0.05);各组CA125水平比较,AB(P0.05),ACD(P0.01),BD(P0.01)。结论:慢性心理应激能干扰下丘脑-垂体-肾上腺轴的功能并导致免疫系统防御功能减弱,对致病因素处于易感状态。当应激发生在肿瘤患者时,可促进肿瘤的发生发展并影响其预后。     

心理应激和体力运动对大鼠海马NE及其合成酶TH、代谢酶MAOA的影响

目的： 本研究通过比较慢性心理应激（以下简称应激）和长期体力运动（以下简称运动）2种过程对大鼠海马去甲肾上腺素（NE)水平及其合成酶酪氨酸羟化酶（TH）和代谢酶单氨氧化酶A（MAOA）的影响,探讨体力运动减缓海马应激损伤的相关机制。方法：动物分别施予自愿跑轮动物模型4周和慢性束缚应激模型3周后,高效液相色谱法比较海马NE变化;蛋白免疫印迹法检测NE合成酶TH、代谢酶MAOA蛋白表达变化。结果：与对照组相比,应激大鼠体重增长缓慢,糖水偏嗜量明显降低,NE水平明显降低［（303.46±24.36) ng/g,P<0.05］,TH、MAOA蛋白表达升高,分别为(1.35±0.94）倍和（2.22±0.62)倍（P<0.05）;运动组大鼠NE水平明显升高｛（418.53±70.64) ng/g,P<0.05］,TH、MAOA蛋白表达亦升高,分别为(1.22±0.59)倍和(1.85±0.36)倍（P<0.05）。结论：结果提示NE水平变化可能与运动减缓应激性海马损伤的关系密切,NE水平的改变与NE的合成与代谢关系不密切,可能存在其它机制。     

Age-dependent changes in noradrenergic locus coeruleus system in wild-type and APP23 transgenic mice

Alzheimer's disease (AD), a neurodegenerative disorder, is characterized by the loss of neurons in specific regions of the CNS including the locus coeruleus (LC), the major noradrenergic locus in the CNS. Several animal models of AD have been developed that exhibit some of the pathophysiological changes in the CNS that are observed in AD patients. The purpose of this study was to determine if the integrity of the LC noradrenergic system is altered in the amyloid precursor protein 23 (APP23) mouse model of AD at the age of 3, 6 and 12 months through quantification of tyrosine hydroxylase (TH) mRNA expression. Despite a previous study suggesting alterations in the noradrenergic transmission system of APP23 mice, the current study failed to show altered TH-positive neuronal numbers or expression in LC noradrenergic neurons of APP23 mice versus wild-type (WT) littermates. However, the present study did demonstrate an age-dependent effect on TH mRNA expression. Both the number of TH-containing neurons and the amount of TH-positive grains/neuron significantly increased between the age of 3 and 6 months with no difference between 6 and 12 months. These observations indicate that any study comparing the noradrenergic system between WT (C57Bl/6) and experimental mice must strictly choose the age to be tested and limit age differences between control and experimental groups to the absolute minimum. More importantly, when long-term therapeutic interventions targeting the noradrenergic system are applied to mouse models, and related parameters are studied longitudinally, care should be taken to distinguish between potential therapeutic and strain-specific developmental or age-related alterations.