Orexin在睡眠-觉醒中的作用机制

Orexins是一组神经肽,分为orexin A、orexin B（OXA、OXB）2种,它们来源于同一前体。Orexins主要由下丘脑外侧区一组特定的神经元产生,通过其神经纤维的直接投射或释放入脑脊髓液作用于靶位点,激活2种G蛋白耦联的细胞表面受体OX1R、OX2R,参与了许多生理活动的调节。其中除了调控摄食行为外,在睡眠-觉醒方面也起着重要的作用。为此,对Orexin在睡眠—觉醒的作用机制作一综述。     

神经肽S对睡眠觉醒的调节

新发现神经肽S (NPS)及其受体(NPSR)构成一新的内源性神经调节系统,NPS-NPSR系统被认为是中枢新的觉醒系统参与睡眠觉醒周期的生理与病理过程.近期研究证明侧脑室注射NPS引起大鼠脑电高频(14.5～60 Hz)活动增强为特征的觉醒时间增加,同时抑制脑电δ波和θ波为特征的慢波睡眠(SWS)和异相睡眠或称为快动眼睡眠(PS/REMS);NPSR拮抗剂[D-Cys(tBu)5] NPS引起大鼠觉醒减少,SWS增加,而不影响PS/REMS. NPSR rs324981单核苷酸多态性和Asn/Ile 107 NPSR多态性与人类的生理性睡眠调节密切相关.机制研究揭示下丘脑结节乳头体核(TMN)91.5％组胺能神经元表达NPSR,TMN注射0.1 nmoL NPS引起大鼠觉醒时间,比侧脑室注射1nmoL NPS引起大鼠觉醒时间显著延长,该作用可分别被NPSR、组胺受体H1R和组胺受体H2R拮抗剂所拮抗,提示NPS神经元投射TMN经NPSR介导激活组胺能神经元是NPS-NPSR调节睡眠觉醒的重要通路.另外,证据表明NPS抗焦虑与抑郁引起睡眠紊乱.为此,揭示NPS能神经元投射途径、作用靶点与突触后神经元作用模式,发现NPSR高效激动剂及拮抗剂将成为今后工作重点.     

Hypocretin的研究新进展

Hypocretin是由外侧下丘脑数千个神经元产生的一种神经肽,外侧下丘脑接受来自边缘系统、皮质下区域等脑区的下行投射和脑干觉醒中枢等上行投射。当产Hypocretin神经元接受信号传入并激活时,合成并释放Hypocretin神经肽。Hypocretin神经肽与其受体结合,可以产生不同的认知和生理功能。目前认为,Hypocretin系统除了与进食有关之外,在维持睡眠觉醒的平衡、奖赏系统和认知功能方面也起着重要的调控作用。     

视前正中核神经元调节睡眠-觉醒的研究进展

 视前正中核(median preoptic nucleus,MnPO)位于下丘脑视前区,主要由GABA能和谷氨酸能神经元组成。研究显示,MnPO在睡眠时大部分细胞放电增加;动物睡眠剥夺后,睡眠张力增高,MnPO区c-Fos表达量增多;毁损大鼠MnPO,睡眠量减少,觉醒量增加。MnPO与脑内多个调控睡眠觉醒的核团有神经纤维联系。在MnPO区微注射GABAA受体激动剂,抑制MnPO神经元,导致觉醒相关脑区神经元去抑制,引起觉醒,提示MnPO区GABA能神经可通过抑制觉醒核团来维持睡眠。本文综述MnPO调节睡眠-觉醒作用的研究进展。       

食欲肽及其对睡眠-觉醒的调节

食欲肽是一种神经肽,在下丘脑分布有大量的食欲肽A和食欲肽B神经元.食欲肽受体有2种亚型OX1R和OX2R,OX2R是2种食欲肽的非选择性受体,OX1R仅对食欲肽A有选择性.食欲肽神经元在人脑的分布与鼠类似.食欲肽除调控摄食行为外,对睡眠与觉醒有重要的调控作用.在调节睡眠-觉醒的相关区域,存在大量的食欲肽受体OX1R和OX2R与高表达的OX1R和OX2R的前体mRNA.食欲肽还与调控觉醒和快波睡眠的神经位点LC、乳结节神经核(TMN)、DR与基底前脑(BF)有复杂的联系,这些区域的食欲肽神经元在觉醒与快波睡眠状态时都异常活跃.食欲肽增多可促进睡眠,食欲肽缺失能诱发发作性睡病.损毁下丘脑某些区域以致食欲肽神经元胞体减少,则可引起睡眠-觉醒功能障碍(如原发发作性睡病等).     

谷氨酸在睡眠和觉醒中的作用研究进展

谷氨酸作为一种兴奋性的神经递质,参与睡眠和觉醒的发生及维持。本文综述了谷氨酸在睡眠和觉醒中的作用,尤其是脑干、外侧下丘脑和基底前脑的谷氨酸在睡眠觉醒中的作用。其中脑干的谷氨酸能既调节清醒时脑活动和肌张力的维持,又调节快速动眼睡眠时相的脑电并引起肌无力;外侧下丘脑的谷氨酸通过激活食欲素神经元,参与外侧下丘脑的唤醒系统;基底前脑的谷氨酸参与脑电去同步化并引起睡眠的减少;而大脑皮层的谷氨酸能神经元不但是觉醒系统的最终作用靶点,而且它本身也可以参与觉醒的调节。同时,谷氨酸能神经元通过与其他类型的神经元的相互作用来调控睡眠觉醒的各个阶段,在脑内组成了一个复杂的睡眠觉醒调节网络,因此不同睡眠觉醒时相的转变,可能存在不同的神经环路机制。文中着重探讨了谷氨酸参与的睡眠觉醒时相转换的神经环路及可能的机制。     

Orexin功能的研究进展

Orexin是由外侧下丘脑神经元产生的一对兴奋性神经肽的合称。近年研究发现,Orexins作用范围广泛,不仅可促进食欲、增强能量代谢,还可影响摄食、能量平衡,睡眠/觉醒、呼吸、脑部创伤的并发症、学习与记忆、食物与药物成瘾、应激、胃肠道功能等,其中尤其在摄食、睡眠/觉醒、学习与记忆方面的作用研究得较多。已有针对Orexin系统的药物研制进入临床阶段。     

下丘脑Hypocretin神经肽在大鼠缰核对睡眠-觉醒调节中的作用

目的：研究下丘脑Hypocretin神经肽在缰核(Hb)对睡眠-觉醒调节中的作用,为探讨Hb在睡眠-觉醒调节中的作用提供理论依据。方法：成年雄性Wistar大鼠20只,随机分为实验组(n=10)和对照组（n=10）,实验组灌胃给予催眠药唑吡坦5 mg•kg^-1,对照组给予等量生理盐水,待唑吡坦药效达峰值时,将大鼠断头处死,取出Hb组织,提取总RNA,采用逆转录聚合酶链反应（RT-PCR）检测Hb中HcrtR2 mRNA的表达水平。另取大鼠(n=5)单侧Hb微量注射霍乱毒素b亚单位(CTb）,采用CTb逆行追踪法观察下丘脑内是否有免疫阳性神经元存在。结果：经RT-PCR检测,实验组和对照组Hb中HcrtR2 mRNA的表达水平（相对平均灰度值分别为0.13±0.03和0.26±0.04）比较差异有显著性（P<0.05）。免疫组织化学染色显示,在大鼠下丘脑外侧区(LHA)、外侧视前区（LPO）和弓状核（ARC）都可见CTb标记免疫阳性神经元。结论：下丘脑Hypocretin神经肽及其受体参与Hb对睡眠-觉醒调节的作用,且Hb接受下丘脑内睡眠相关结构LHA、LPO、ARC的纤维投射。     

交泰丸对睡眠剥夺大鼠下丘脑Orexin A及γ-氨基丁酸的影响

【目的】观察交泰丸对快速动眼（REM）睡眠剥夺大鼠下丘脑神经递质Orexin A及γ-氨基丁酸（GABA）的影响。【方法】采用水环境小平台法制备大鼠睡眠剥夺模型,将造模成功的大鼠随机分为6组,即交泰丸高、中、低剂量组（剂量分别为18.6、9.3、4.6 g/kg）,地西泮组（剂量为3 mg/kg）、模型组及正常组,采用酶标仪吸光度法检测大鼠下丘脑促觉醒神经递质Orexin A,高效液相法库伦电化学检测大鼠下丘脑促睡眠神经递质GABA。【结果】与正常组比较,模型组大鼠完全处于失眠状态,其下丘脑Orexin A含量显著升高（ P<0.05）;与模型组比较,交泰丸高、中、低剂量组失眠状态有明显改善, Orexin A含量显著降低（P<0.05）;与模型组比较,交泰丸高、中、低剂量组GABA含量无显著变化（P＞0.05）。【结论】交泰丸的镇静催眠作用可能是通过抑制大鼠下丘脑促觉醒神经递质Orexin A实现的。     

兴奋和抑制下丘脑背内侧核对大鼠睡眠的影响

目的 观察兴奋和抑制大鼠下丘脑背内侧核团(DMH)对睡眠觉醒周期的影响。方法 采用脑立体定位、核团微量注射和多导睡眠描记技术。结果 DMH微量注入兴奋性神经递质L-谷氨酸引起睡眠减少,觉醒增加;DMH微量注入抑制性神经递质γ-氨基丁酸引起觉醒减少,睡眠增加。结论 DMH参与觉醒睡眠周期的调节,其神经元兴奋具有促觉醒作用。     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

Development on Adjustable Calibration Marker for Shock Wave Focus

Shock wave lithotripsy （SWL） is a treatment of choice for upper urinary stones. However, this procedure is inappropriate for obese patients because the focus is often unable to reach the target owing to the limited focal distance in shock wave source. Although treating such patients in a blast path may increase the application length of shock wave source, it＇s difficult to find this path on the lithotripter monitor. For this reason, we invented an adjustable calibration marker in order to set an effective focus in the shock wave hath.     

Study on the TCM Pathogenesis of Angiopathic Complications of Type II Diabetes

Excess production of reactive oxygen species(ROS)of mitochondrion mediated by hyperglycemia is the common pathogenesis of angiopathic complications of diabetes.TCM holds that the damp from the dysfunction of spleen.kidney and liver is the causative factor of complications of diabetes.This is similar to the mechanism of Ros resulting in angiopathic complications of diabetes.When the angiopathic complications of type II diabetes mellitus(T2DM)are difierentiated as caused by turbid damp in TCM can be explained as ROS.Since the obstruction of pathogenic damp in channels and collaterals is said to be the main pathogenesis,the treating principle should be dissolving the damp to remove the obstruction.     

Leptin, Ghrelin and TNF-α before and after Hypo-caloric Traditional Chinese Diet and Auricular Acupuncture

INTRODUCTION Obesity is a complex emergent problem, which can be possibly solved not only by the diet but also by the life style and promotion of a constant physical exercise. 1, 2 No doubt careful attentions must be given to the nutritional condition of obese people, the dietary habits, the somatic build (i.e. distribution of fat mass) and the organic functions linked to formation of the fat mass. All the parameters should be constantly monitored before, during and after a diet treatment. 3, 4, 5     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

Relationship between Dysglycemia and Carotid Atherosclerosis in Tibetan Population

People with dysglycemia are at high risk for atherosclerotic diseases. This study aims at investigating the atherosclerotic vascular damage in dysglycemia and its metabolic origin in Tibetan population.     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

CLINICAL SIGNIFICANCE OF SERUM CYTOKINES IL-1β,sIL-2R,IL-6,TNF-α,AND IFN-v IN ACUTE CORONARY SYNDROME

Objectives To explore serum cytokines levels (including IL-1 β, sIL-2R, IL-6, TNF-α, and IFN-v) and their significance in patients with acute coronary syndrome (ACS) and the subsequent follow-ups, with attempt to estimate the role of various serum inflammatory markers in the diagnosis and assessment of ACS.Methods The study population include 40 patients with acute myocardial infarction (AMI), 40 patients with unstable angina pectoris (UAP), and 40 controls. Among the 80 patients, 60 patients attended a follow up 4 months later. Serum inflammatory markers including IL-1 β, sIL-2R, IL-6, TNF-α, and IFN-v were measured by enzyme linked immunosorbent assay.Results Serum IL- 1 β, sIL-2R, IL-6, TNF-α were significantly higher in AMI group or UAP group compared to the control group and became significantly lower 4 months later in the follow-up patients. Serum levels of IFN-v shows no significant difference between AMI group or UAP group and controls, also showing no significant change when measured in follow up patients. There was no correlation between serum creatine kinase-MB isoenzyme levels and serum inflammatory markers either in UAP or AMI group. Furthermore, when divided into two subgroups using Wagner's QRS scoring system in the AMI group, there is no difference of each serum inflammatory marker between ≤ 6 scores group and ＞ 6 scores group.Conclusion Serum levels of certain inflammatory markers may have some diagnostic value for ACS, and can be a useful marker reflecting disease stability.     

Possible Spread of adenovirus type 3 from poultry to humans ：indirect evidence from an outbreak in China

Objective:To explore the epidemiology and etiology for an outbreak of acute respiratory tract infection that occurred in one county of Jiangsu Province, China 2004. Methods: Only cases meeting the case definition were included in the study. We reviewed the medical records of the cases who were admitted to the local hospitals, interviewed cases by a standard questionnaire, and then described the epidemiotogic features and analyzed risk factors by means of a case-control study. We collected pharyngeal swab specimens and sent them to different laboratories for isolation and culture. The laboratory used different detection methods such as DIP, PCR, electron microscope examination and microneutralization assay, to identify and then type the positive specimens. Results:A total of 871 cases were reported during the period from April 18 to July 4,2004. The distribution of onset times presented two peaks, one in late May and another in middle June. The epidemic occurred mainly in the elementary and junior high schools in ten townships of one county, and the mean age of the cases was 12 years (range 7 months to 18 years). The course of the disease was acute, and was characterized by fever accompanied with sore throat and tonsillitis. The WBC count of cases was normal or elevated. The mean duration of illness was 5 days (range 2 to 12 days). No fatalities from illness were reported. A case-control study indicated that the possible risk factors were close contact with a case and/or poultry before onset and sharing of towels among members of the family. The typical CPE was observed through inoculating pharyngeal swab specimens into the HEP-2 cell cultures in different laboratories. An infection of adenovirus type 3 was verified by detecting positive specimens in different methods. Conclusion:This investigation demonstrated that the acute respiratory infection in cases was caused by adenovirus type 3. Cases occurred in over 70 schools in ten townships in 2004, and the route of transmission was possibly close contact with cases or droplet transmission.