胰岛素在大鼠深慢波睡眠调节中的作用

目的 探讨胰岛素对大鼠睡眠特别是深慢波睡眠的影响. 方法根据SD大鼠海马CA1区注射试剂及剂量的不同,分为对照组、0.05 IU胰岛素组、0.1 IU胰岛素组和0.2 IU胰岛素组;采用脑立体定位、核团插管、微量注射和多导睡眠描记技术观察海马CA1区微量注射胰岛素对大鼠睡眠-觉醒周期的影响. 结果海马CA1区微量注射0.05 IU的胰岛素对大鼠睡眠-觉醒周期及睡眠的深度无明显影响.微量注射0.1 IU的胰岛素后,觉醒时间减少,总睡眠时间增多;与对照组比较,慢波睡眠时间增加18.1%(P<0.05),且主要是浅慢波睡眠成分增加22.0%(P<0.01).微量注射0.2 IU的胰岛素后,觉醒时间减少,总睡眠时间增多,睡眠加深;与对照组比较,慢波睡眠时间增加29.8%(P<0.01),其中浅慢波睡眠时间增加21.6%(P<0.01),深慢波睡眠时间增加53.2%(P<0.05).结论 胰岛素在海马参与睡眠的调节且具有促眠作用,胰岛素对大鼠睡眠深度的影响与注射的剂量呈正相关.     

海马CA1区注射吗啡对大鼠睡眠的影响

目的观察吗啡在海马CA1区对大鼠睡眠的影响。方法选择雄性成年SD大鼠39只,分为对照组(8只)、吗啡组(8只)和纳洛酮组(8只),15只不符合要求已剔除。运用脑立体定位、核团插管、药物微量注射和多导睡眠描记技术,观察海马CA1区注射药物后大鼠睡眠-觉醒指标变化情况。结果与对照组比较,吗啡组大鼠海马CA1区双侧微量注射吗啡后觉醒时间增加32.0%(P<0.05),总睡眠时间减少23.7%(P<0.05),其中深慢波睡眠减少76.1%(P<0.05)。纳洛酮组大鼠海马CA1区双侧微量注射纳洛酮后觉醒时间减少34.1%(P<0.01),总睡眠时间增加25.3%(P<0.01),其中深慢波睡眠增加247.8%(P<0.01)。结论吗啡在海马参与对睡眠-觉醒周期的调节,且吗啡对睡眠的影响主要是通过改变深慢波睡眠成分实现的。     

淫羊藿总黄酮对大鼠睡眠-觉醒影响的观察

目的 观察侧脑室注射淫羊藿总黄酮(total flavonoids of Epimedium,TFE)对大鼠睡眠和觉醒活动的影响.方法 运用脑立体定位技术进行TFE的侧脑室微量注射,通过多导睡眠描记术(PSG)观察TFE对大鼠睡眠-觉醒活动的影响.结果 侧脑室注射TFE引起大鼠慢波睡眠时间(SWS)和总睡眠时间(TST)增多,觉醒(W)时间减少;侧脑室注射荷包牡丹碱(Bic)可增加W,减少快波睡眠(PS);侧脑室同时注射TFE和Bic则对睡眠和W无显著效应.结论 TFE可促进睡眠,抑制觉醒,即TFE具有明显的中枢抑制作用.     

新型IL-10抑制剂对睡眠剥夺大鼠的影响

目的 研究不同剂量AS101对于6 h睡眠剥夺后大鼠睡眠觉醒周期的影响.方法 采用脑立体定位、脑电图、肌电图记录方法 观察AS101对于睡眠剥夺大鼠睡眠反跳的影响.结果 6 h睡眠剥夺后,与注射缓冲液组(PBS)大鼠比较,0.5 mg/kg AS101可以增加觉醒时间和减少慢波睡眠时间,可将快眼动睡眠从(54.53±14.61)min减少到(34.4±17.34)min(P＜0.05).结论 AS101可能参与大鼠睡眠觉醒周期的调节.     

舒郁安神方对老年肝郁失眠证候模型大鼠学习记忆及脑组织谷氨酸、γ-氨基丁酸含量的影响

目的 探讨舒郁安神方对老年肝郁失眠证候模型大鼠学习记忆及脑内谷氨酸(Glu)、γ-氨基丁酸(GABA)含量的影响.方法 采用腹腔注射D-半乳糖+夹尾刺激+睡眠剥夺复制并评价老年肝郁失眠证候大鼠模型.然后采用水迷宫实验检测各组大鼠学习记忆能力,采用高效液相色谱法检测大脑皮质及下丘脑Glu及GABA含量的变化.结果 与空白对照组比较,证候模型组大鼠学习记忆水平显著下降(P<0.01),大脑皮质及下丘脑Glu及GABA含量显著升高(P<0.01,P<0.05),且Glu/GABA比值增高,经舒郁安神方干预后各指标趋于正常范围.结论 舒郁安神方能增强老年肝郁型失眠证候模型大鼠学习记忆能力,其机制可能与减少脑内氨基酸毒性作用有关.     

五味子木脂素对氯苯丙氨酸致失眠大鼠的催眠作用

目的观察五味子总木脂素对氯苯丙氨酸(PCPA)所致失眠大鼠的催眠作用并探讨相关机制。方法将雄性Wistar大鼠随机分为4组,空白对照组(CON组,灌胃蒸馏水,注射生理盐水),模型组(MOD组,灌胃蒸馏水,注射PCPA),SCL组(灌胃SCL,注射PCPA)及PCPA+SCL组(灌胃SCL,注射PCPA)。连续灌胃给药7 d,每天1次。通过阈下剂量戊巴比妥钠协同睡眠试验观察各组大鼠睡眠只数;通过阈剂量戊巴比妥钠协同睡眠试验观察各组大鼠睡眠潜伏期及睡眠持续时间。应用酶联免疫吸附试验观察各组下丘脑5-羟色胺(HT)及5-羟吲哚乙酸(HIAA)水平。结果与CON组比较,MOD组睡眠只数减少,睡眠潜伏期显著延长,睡眠时间显著缩短,下丘脑5-HT及5-HIAA水平显著降低(P<0.05或P<0.01);SCL组睡眠只数增多,睡眠潜伏期显著缩短,睡眠时间显著延长,下丘脑5-HT及5-HIAA水平显著升高(P<0.05或P<0.01);与MOD组比较,PCPA+SCL组睡眠只数增多,睡眠潜伏期显著缩短,睡眠时间显著延长,下丘脑5-HT及5-HIAA水平显著升高(P<0.05或P<0.01)。结论五味子木脂素对PCPA所致失眠大鼠具有催眠作用,该作用与其调节大鼠下丘脑5-HT及5-HIAA水平有关。     

奥氮平对首发精神分裂症患者睡眠障碍的影响

目的 通过观察首发精神分裂症患者多导睡眠图(Polysomnogram,PSG)指标来探讨奥氮平对首发精神分裂症患者睡眠情况的影响。方法 对40例住院精神分裂症患者奥氮平治疗前和治疗4周后进行多导睡眠图监测描记,并和40名健康自愿者进行对比。结果 与正常对照组相比,奥氮平组治疗前总睡眠时间减少,睡眠潜伏期延长,睡眠效率下降,觉醒时间增多,快动眼(REM)睡眠潜伏期缩短,REM睡眠时间、慢波睡眠(SWS)睡眠时间减少,差异有显著的统计学意义(P＜0.01)。服药4周后奥氮平组较基线总睡眠时间延长,REM睡眠时间增多,REM睡眠潜伏期延长,觉醒时间减少,睡眠效率提高,差异有显著的统计学意义(P＜0.01)。 结论 精神分裂症患者存在睡眠结构和睡眠连续性两方面的异常,奥氮平能改善首发精神分裂者患者的客观睡眠情况。     

GABA受体基因转染对癫痫大鼠海马CX32表达的影响

目的 探讨在下丘脑乳头体上核内转染γ-氨基丁酸(GABA)受体基因后对海人酸(KA)致痫大鼠海马区缝隙连接蛋白32(CX32)表达的影响.方法 在右侧杏仁核内注射KA制备癫痫动物模型作对照组,GABA基因转染组则利用仙台病毒(HVJ)-脂质体转染法预先在下丘脑的乳头体上核内转染被脂质体包被的GABA受体基因,48 h后在杏仁核内注射KA,两组大鼠分别进行CX32原位杂交观察.结果 GABA基因转染组大鼠CX32表达在各个时程均有下降.结论 下丘脑内转染GABA受体基因后可以抑制癫痫发作的程度.     

阻塞性睡眠呼吸暂停综合征患者慢波睡眠与清晨血压的关系

目的探讨阻塞性睡眠呼吸暂停综合征(OSAS)患者慢波睡眠与清晨血压的关系。方法以2014年1月至2015年12月首次确诊为OSAS的连续病例90例为研究对象,每例均行24 h动态血压监测(ABPM),将OSAS未合并清晨及夜间高血压者作为对照组(41例),OSAS合并清晨高血压而无夜间高血压者为清晨高血压组(14例),OSAS合并清晨及夜间高血压者为持续高血压组(35例),比较3组间的血压差异。分别观察3组之间的睡眠参数[睡眠呼吸暂停低通气指数(AHI)、氧减指数、慢波睡眠比例、唤醒指数、睡眠效率等],并分析OSAS患者清晨血压与各睡眠参数(AHI、氧减指数、慢波睡眠比例、唤醒指数、睡眠效率等)的相关性。结果与对照组和清晨高血压组相比,持续高血压组的AHI[(39.7±25.1)比(30.1±17.7)、(25.4±16.5)次/h]、唤醒指数[(30.3±20.7)比(22.7±12.6)、(18.8±10.1)次/h]、4%氧减指数[(26.1±18.7)比(19.3±14.2)、(12.9±12.7)次/h]、3%氧减指数[(30.8±18.5)比(25.6±13.7)、(18.4±14.8)次/h]较高,而清晨高血压组与持续高血压组的慢波睡眠比例[(9.1±4.6)%、(11.3±7.4)%比(15.5±7.1)%]较对照组低(均P0.05)。单因素相关分析显示,清晨收缩压与慢波睡眠比例(r=-0.293)、睡眠效率(r=-0.246)呈负相关,与年龄(r=0.235)、夜间血氧90%的时间占总睡眠时间的百分比(TS90%)(r=0.033)呈正相关(均P0.05)。逐步回归分析提示,年龄和慢波睡眠比例均对清晨收缩压的影响有统计学意义(β值分别为0.212和-0.259,均P0.05)。结论在众多OSAS患者睡眠参数中仅慢波睡眠比例与清晨血压相关,睡眠时慢波睡眠时间较短是清晨高血压的危险因素。     

p38MAPK信号通路与睡眠剥夺的表达及意义

目的探讨p38磷酸化激酶信号转导通路(MAPK)在大鼠睡眠剥夺中的作用及与炎症因子的关系。方法将40只雄性Wistar大鼠随机分为对照组、大平台组、睡眠剥夺组、抑制剂组,每组10只。采用免疫组化观察大鼠海马区白介素(IL)-1β和磷酸化p38MAK的表达,同时利用水迷宫检测大鼠认知功能。结果与对照组和大平台组对比,睡眠剥夺组IL-1β与磷酸化p38MAPK表达明显上调(P<0.05),抑制剂组显著下降(P<0.05)。认知功能评价中睡眠剥夺组明显低于对照组和大平台组(P<0.05),抑制剂治疗组明显改善(P<0.05)。结论 p38信号转导通路参与了大鼠睡眠剥夺的过程,且可引起炎症因子的释放,该作用可影响大鼠认知功能。     

Keratinocyte growth factor gene therapy ameliorates ulcerative colitis in rats

AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5%(v/v) acetic acid.Twenty-four hours after exposed to acetic acid,rats were divided into three experimental groups:control group,attenuated Salmonella typhimurium Ty21a strain(SP) group and SP strain carrying human KGF gene(SPK) group,and they were separately administered orally with 10% Na...     

Effect of substance P on Rat gastrointestinal transit

The in vivo effect of substance P and related peptide analogs on gastrointestinal transit in unanesthetized rats was studied. Fasted male rats were given intragastrically 0.5 ml of a powdered charcoal (BaSo4.H2O) meal and were concomitantly injected intraperitoneally with 8 micrograms/kg of substance P or a related peptide. In control rats, the percentage of small intestine traversed by the meal 15 min after feeding was 44.9 +/- 1.4 (N = 12). Substance P, [pGlu6]SP, [pGlu6, gPhe8, mGly9]SP and [pGlu5, N-MePhe8, N-MeGly9]SP significantly accelerated intestinal transit: 59.5 +/- 3.1% (N = 7); 66.0 +/- 3.8% (N = 14), 66.8 +/- 2.4% (N = 25), and 58.4 +/- 4.4% (N = 4), respectively. Concomitant injection of [pGlu6]SP and BOC-Phe-Phe-Gly-NHOH, an inhibitor of enzyme degradation at a dose of 800 micrograms/kg lowered by 10-fold the dose of [pGlu6]SP needed to induce the same degree of intestinal transit acceleration. These results indicate that in rats, substance P and related peptides accelerate gastrointestinal transit.     

Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: role of vascular superoxide anion formation and endothelial nitric oxide synthase expression.

OBJECTIVES: We sought to investigate the effects of adding spironolactone (SP) to angiotensin-converting enzyme (ACE) inhibition on endothelium-dependent vasodilation in rats with chronic heart failure (CHF). BACKGROUND: Adding SP to ACE inhibitors reduces mortality and morbidity in CHF. Endothelial vasomotor dysfunction contributes to increased peripheral vascular resistance and reduced myocardial perfusion in CHF. METHODS: Seven days after extensive myocardial infarction (CHF) or sham operation, Wistar rats were treated with placebo, the ACE inhibitor trandolapril (TR, 0.3 mg/kg body weight per day), SP (10 mg/kg per day) or a combination of both for 11 weeks. RESULTS: Maximal acetylcholine-induced, nitric oxide (NO)-dependent relaxation was significantly attenuated in aortic rings from rats with CHF as compared with sham-operated animals (R(max) 44 +/- 3% vs. 63 +/- 3%). Spironolactone alone had no influence (46 +/- 5%) and TR improved NO-mediated relaxation (55 +/- 4%), whereas treatment with both completely restored endothelium-dependent vasorelaxation (64 +/- 4%). Aortic superoxide formation was significantly increased in rats with CHF as compared with sham-operated animals, but was normalized by treatment with SP or SP plus TR. In addition, aortic messenger ribonucleic acid expression of the oxidase subunit p22(phox) in rats with CHF was significantly reduced by SP or TR plus SP. Endothelial NO synthase expression was increased in TR-treated animals. Incubation of isolated porcine coronary arteries with SP dose-dependently attenuated superoxide formation. CONCLUSIONS: Spironolactone added to an ACE inhibitor normalizes NO-mediated relaxation in experimental CHF by beneficially modulating the balance of NO and superoxide anion formation.     

Effects of electroacupuncture on cardiac and gastric activities in acute myocardial ischemia rats

AIM： To observe the effect of electroacupuncture （EA） of ＂Neiguan＂ （PC6） and ＂Gongsun＂ （SP4） on pathological changes of the heart and stomach in rats with acute myocardial ischemia （AMI）, and to explore its underlying mechanism. METHODS： Fifty Wistar rats were randomized into control, model, PC6, SP4 and PC6 ＋ SP4 groups （n = 8 each group）. An AMI model was established by occlusion of the descending anterior branch （DAB） of the left coronary artery. ECG-ST of cervico-thoracic lead and electrogastrogram （EGG） were recorded. EA was applied to PC6, SP4 and PC6 ＋ SP4 groups, respectively. At the end of experiments, the rats were transcardicalty perfused with 4% paraformaldehyde, and the heart base myocardium, gastric antrum and duodenum tissues were sampled, sectioned and stained with a reduced form of nicotinamideadenine dinucleotide phosphate （NADPH）-diaphorase histochemical method for displaying nitric oxide synthase （NOS） activity. RESULTS： After AMI, ECG-ST values elevated. After EA, the elevated ECG-ST values at 20 min in PC6group, at 30 min in PC6 ＋ SP4 and SP4 groups had no significant differences in comparison with their respective basal values before AMI. Following AMI, the amplitude and frequency of slow waves of EGG decreased remarkably （P 〈 0.05）. At 30 min after EA, the mean amplitude and frequency of slow waves of EGG in the three EA groups had no marked differences compared with their individual basal levels and those in the control group. After AMI, the mean integral grey values of NOS-positive product in myocardium, gastric antrum and duodenum tissues in the model group increased remarkably in comparison with the control group, while those in three EA groups were lower than those in the model group. No significant differences were found in ECG-ST and EGG improvement among the three EA groups. However, EA of PC6 had a better effect on ECG-ST and EA of PC4 had a better effect on EGG, respectively. CONCLUSION： EA of PC6, SP4 and PC6 ＋ SP     

螺旋藻对高同型半胱氨酸血症的干预作用

目的:研究螺旋藻(spirulina,SP)对大鼠高同型半胱氨酸血症(hyperhomocysteinemia,HHcy)的影响。方法:60只雄性Wistar大鼠随机分成6组,每组10只,包括:正常对照组、HHcy模型组、SP低剂量干预组(0.5g/kg·d)、SP中剂量干预组(1.5g/kg·d)、SP高剂量干预组(3.0g/kg·d)和叶酸干预组(5.0mg/kg·d)。除正常对照组外,其余各组均以L-蛋氨酸灌胃(1g/kg·d);各干预组均给予相应药物处理。连续喂养12周后,以高效液相色谱法测定血浆同型半胱氨酸(homocysteine,Hcy)水平,以氧化酶法测定血浆总胆固醇(TC)、甘油三酯(TG)浓度,以硫代巴比妥酸反应比色法测定血浆丙二醛(MDA)水平。结果:HHcy模型组血浆Hcy水平,TC、TG浓度和MDA水平明显高于正常对照组(P均<0.001)。给予SP低、中、高剂量和叶酸干预后,大鼠血浆Hcy水平较模型组明显下降(P均<0.05),其中以SP中剂量组下降最为明显,较叶酸组明显下降(P<0.05),其水平达正常对照组水平(P>0.05);叶酸组HHcy水平亦显著下降(P<0.05);TC、TG、MDA浓度亦均显著下降(P<0.001),达正常水平(与正常对照组相比P均>0.05)。结论:一定剂量的螺旋藻能有效降低大鼠血浆Hcy浓度,使其达到正常水平,其效果优于叶酸治疗;螺旋藻还能纠正HHcy所引起的血脂代谢紊乱,并降低HHcy引起的氧化应激水平。     

软脂酸通过丝裂原活化蛋白激酶通路促进血管内皮细胞凋亡

目的探讨软脂酸(PA)诱导的血管内皮细胞凋亡中丝裂原活化蛋白激酶(MAPK)通路的作用。方法将人脐静脉内皮细胞(HUVEC)分对照组、PA组、MAPK通路干预组[分别先用p38抑制剂SB203580、氨基末端激酶(JNK)抑制剂PD98059、细胞外信号调节激酶(ERK)抑制剂SP600125干预]再分为PA+SB组、PA+PD组、PA+SP组。流式细胞仪检测细胞凋亡率;Western blot法检测caspase-3、磷酸化p38、JNK和ERK1/2表达水平;分光光度法检测caspase-3的活性。结果与对照组比较,PA组、PA+SB组、PA+PD组、PA+SP组HUVEC凋亡及caspase-3表达和活性明显增加,PA组磷酸化p38MAPK表达明显增加(P<0.05)。与PA组比较,PA+SB组HUVEC细胞凋亡率、caspase-3表达和活性明显降低(P<0.05);而PA+PD组和PA+SP组HUVEC凋亡率、caspase-3表达和活性无明显变化(P>0.05)。结论 PA通过p38MAPK通路促进内皮细胞凋亡。     

PTH regulation of c-Jun terminal kinase and p38 MAPK cascades in intestinal cells from young and aged rats

In the present study, we examined the role of Parathyroid hormone (PTH) on the c-Jun N-terminal kinase (JNK) 1/2 and p38 mitogen-activated protein kinase (MAPK) members of the MAPK family as it relates to ageing by measuring hormone-induced changes in their activity in enterocytes isolated from young (3 month old) and aged (24 month old) rats. Our results show that PTH induces a transient activation of JNK 1/2, peaking at 1 min (+threefold). The hormone also stimulates JNK 1/2 tyrosine phosphorylation, in a dose-dependent fashion, this effect being maximal at 10 nM. PTH-induced JNK 1/2 phosphorylation was suppressed by its selective inhibitor SP600125. Moreover, hormone-dependent activation of JNK 1/2 was dependent on calcium, since pretreatment of cells with BAPTA-AM or EGTA blocked PTH effects. With ageing, the response to PTH was significantly reduced. JNK basal protein expression was not different in the enterocytes from young and aged rats, however, basal protein phosphorylation increased with ageing. PTH did not stimulate, within 1–10 min, the basal activity and phosphorylation of p38 MAPK in rat intestinal cells. The hormone increased enterocyte DNA synthesis; the response was dose-dependent and decreased (-40%) with ageing. In agreement with the mitogenic role of the MAPK cascades, this effect was blocked by specific inhibitors of extracellular signal-regulated protein kinase (ERK) 1/2 and JNK 1/2. The results obtained in this work expand our knowledge on the mechanism of action of PTH in duodenal cells.     

Preptin对人成骨细胞增殖和分化的影响及机制研究

目的 探讨preptin对人成骨细胞增殖和分化的影响及其信号途径.方法 体外培养人成骨细胞,用10-10、10-9、10-8和10-7mol/L preptin干预24 h,以[3H]脱氧胸腺嘧啶苷掺入法分析细胞增殖,用分光光度计法测定细胞碱性磷酸酶(ALP)活性判断细胞分化程度.Western印迹法检测细胞外信号调节激酶(ERK)、p38丝裂原活化蛋白激酶(p38MAPK)和c-Jun氨基末端激酶(JNK)的磷酸化水平.并在preptin干预前以ERK抑制剂(PD98059)、p38 MAPK抑制剂(SB203580)和JNK抑制剂(SP600125)预处理,观察preptin诱导人成骨细胞增殖和分化的途径.结果 Preptin剂量依赖地增加人成骨细胞的增殖和ALP活性,10-9mol/L浓度时达最大效应(均P<0.01).Preptin刺激人成骨细胞ERK的磷酸化,对p38MAPK和JNK无作用.PD98059阻断preptin刺激的成骨细胞增殖及ALP活性增加(均P<0.05),而SP600125和SB203580无此效应.结论 Preptin通过ERK途径促进人成骨细胞的增殖和分化.