限钠或补钠对充血性心衰大鼠心钠素及心功能的影响

目的：观察限钠或补钠对充血性心衰大鼠心钠素及心功能的影响。方法：将充血性心衰大鼠随机分为3组（心衰组、心衰限钠组、心衰补钠组J）,假手术大鼠为对照组,用放射免疫分析法测定各组血浆和心肌心钠素水平,同时检测心功能。结果：心衰限钠组血钠、心房心钠素及左室收缩压和动脉压显著低于心衰组,血浆和心室心钠素、右房压均显著高于心衰组;心衰补钠组血钠和动脉压与对照组无显著差别,血浆和心肌心钠素、右房压与心衰组无显著差别,左室收缩压显著高于心衰组,左室舒张末压显著低于心衰组。结论：心衰后适量补钠维持血钠平衡有利于心钠素发挥排钠利尿作用,改善心功能。     

大鼠急性肾衰时心钠素含量及有关因素的变化

大鼠急性肾衰时心钠素含量及有关因素的变化天津市医药科学研究所（天津３０００７０）陈宁，杨国林，王玉芬，袁玲，潘焰目前肾脏病学的研究内容已不仅限于肾脏的几种疾病，而且涉及到机体与肾脏有关的其他系统的许多问题和疾病。在我国也已有不少关于慢性肾功能衰竭患者...     

胰岛素抵抗大鼠骨骼肌蛋白激酶B的表达

蛋白激酶B(pmtein kinaseB,PKB)具有促进生长、增殖、抑制凋亡的作用,对糖代谢有明显影响。本研究通过高脂喂养诱导sprague-Dawley(SD)大鼠产生胰岛素抵抗,检测大鼠骨骼肌中胰岛素诱导的蛋白激酶B的表达的改变,揭示胰岛素抵抗与蛋白激酶B表达的关系。     

一肾一夹和两肾一夹高血压和血压逆转大鼠血浆、心房和心室心钠素水平的变化特征

利用一肾一夹容量型和两肾一夹压力型大鼠肾血管性高血压所敛心肌肥厚及高血压逆转肥厚逆转模型,测定血浆、心房和心审心钠素水平。发现两型高血压大鼠血浆及左室的心钠素水平明显增高,左室及血浆心钠素浓度与相对室重呈正相关,左房心钠素浓度在一肾一夹型明显降低;随着高血压的逆转,两型大鼠血浆及心房心钠素水平基本恢复,增高了的心室心钠素由高水平下降。结果提示。在高血压、容量扩张并伴有心肌肥厚的病理情况下,心室心钠素可能起重要的代偿调节作用。     

松果体及褪黑素对大鼠胸腺巨噬细胞酪氨酸激酶受体B表达的影响

目的:研究松果体摘除及补充褪黑素对大鼠胸腺巨噬细胞酪氨酸激酶受体B(trkB)表达的影响.方法:选用2月龄清洁级SD大鼠,分为正常对照组、假手术对照组、松果体摘除组、松果体摘除+褪黑素注射7.5mg·kg~(-1)·d~(-1)组和松果体摘除+褪黑素腹腔15mg·kg~(-1)·d~(-1)组,术后4、 8周取材.应用trkB和单克隆抗体ED1免疫荧光双标显色法观察分析松果体摘除及补充外源性褪黑素后胸腺巨噬细胞trkB表达的变化.结果:与对照组相比,松果体摘除术后4周胸腺双阳性细胞表达减弱,补充褪黑素后无变化.术后8周松果体摘除组与对照组相比无明显差异,而低剂量组双阳性细胞表达异常增高,高剂量组恢复正常.各组平均灰度无明显差异.结论:松果体及褪黑素在影响胸腺细胞分化发育过程中,胸腺巨噬细胞表达的trkB也随之发生变化,其与胸腺细胞表达的trkB共同作用参与胸腺细胞分化发育.胸腺神经内分泌微环境的分泌调节是松果体及褪黑素保护胸腺细胞的通路之一.     

牵张预适应对牵张致大鼠心律失常的抑制作用

的:通过观察增加大鼠左室后负荷引起心肌单向动作电位(MAP)改变来研究牵张预适应对牵张导致心律失常的影响。方法:采用部分夹闭大鼠主动脉根部以增加左室后负荷的在体心脏模型,观察预牵张和再次牵张过程中左心室肌MAP及左室压力的变化。结果:预牵张引起心律失常及一段短暂的时间依赖性机械电适应期。牵张预适应依赖于两次牵张间期。结论:牵张预适应具有时间依赖性地抗牵张导致心律失常的作用。心室肌的“机械电适应期”可能为临床上心律失常治疗提供新的思路。     

低脂饮食和有氧运动干预对高脂大鼠脂肪组织蛋白激酶B表达的影响

目的 :观察低脂饮食和有氧运动对高脂大鼠脂肪组织中蛋白激酶B(PKB)表达的影响。方法 :选取雄性Wistar大鼠 4 0只 ,随机分为正常对照组 ( 10只 )和模型组 ( 30只 )。模型组大鼠给予高脂喂养 ,4周后 ,再随机分为 3组 :胰岛素抵抗组 ,继续高脂饮食 ;低脂饮食组 ,给予低脂饮食 ;有氧运动组 ,继续高脂饮食 +有氧运动。干预 6周后 ,蛋白印迹法检测大鼠脂肪组织中胰岛素刺激PKB表达的含量变化。结果 :低脂饮食组和有氧运动组大鼠空腹血糖 (FBG)、甘油三酯 (TG)、胆固醇 (TC)、内脏脂肪及胰岛素抵抗指数 (HOMA IR)下降 ,胰岛素敏感指数 (ISI)显著升高。而PKB蛋白表达分别增加了 16 .1%和 19.2 %(P <0 .0 1)。结论 :低脂饮食和有氧运动能改善胰岛素抵抗 ,可能与增加脂肪组织中PKB蛋白表达有关。     

牵张刺激诱导心肌细胞NF-κB的激活与转位

应用免疫组化方法观察牵张刺激对心肌细胞中NF-κB分布的影响,探讨牵张刺激对心肌细胞NF-κB的激活作用.结果显示,未受牵张与牵张1小时的心肌细胞中,NF-κB位于胞浆,牵张3小时的心肌细胞中NF-κB位于胞浆及核膜周围,牵张5小时的心肌细胞中,NF-κB位于胞核.表明心肌细胞受到一定的牵张刺激后,NF-κB可以被激活而由胞浆转位到胞核.     

大鼠窦状卵泡颗粒细胞中磷酸化蛋白激酶B表达与凋亡的关系

目的探讨大鼠窦状卵泡中磷酸化蛋白激酶B(PKB,又称Akt)的表达与卵泡颗粒细胞凋亡之间的关系。方法应用免疫组织化学法和Western blot法检测磷酸化Akt(phosphorylation-Akt,p-Akt)在大鼠不同发育阶段卵泡颗粒细胞中的表达,应用TUNEL法检测成年大鼠卵泡颗粒细胞的凋亡情况。结果在大鼠窦前及窦状卵泡的颗粒细胞中,p-Akt表达高的颗粒细胞凋亡程度较轻,而p-Akt低表达的颗粒细胞凋亡现象较明显。结论 p-Akt的高表达在一定程度上与颗粒细胞凋亡受抑制有关,并有可能参与了窦状卵泡阶段卵泡的闭锁的选择。     

慢性阻塞性肺疾病大鼠中磷酸化蛋白激酶B与γ-谷氨酰半胱氨酸合成酶的表达研究

目的通过观察慢性阻塞性肺疾病（COPD）大鼠模型中γ-谷氨酰半胱氨酸合成酶（γ-GCS）与磷酸化蛋白激酶B（p-PKB）的表达,研究p-PKB和γ-GCS在COPD中可能的参与机制。方法28只健康雄性Wistar大鼠随机分为COPD组和对照组。采用每日熏香烟和两次气管内注入脂多糖（LPS）法制作COPD大鼠模型。检测肺组织中1-GCS活性,原位杂交检测肺组织中γ-GCS mRNA的表达,免疫组化和Western印迹分析肺组织中γ-GCS与p-PKB蛋白水平。结果γ-GCS活性在COPD组大鼠中明显高于对照组,组间差异有统计学意义（P〈0．05）。原位杂交显示COPD组大鼠支气管、肺泡上皮细胞与小动脉平滑肌细胞γ-GCS mRNA广泛表达,与对照组比较差异有统计学意义（P〈0．05）。COPD组大鼠γ-GCS与p-PKB免疫组化可见肺泡、支气管壁细胞及小血管平滑肌细胞胞浆有较强蛋白阳性信号;图像定量分析显示COPD组γ-GCS与p-PKB蛋白表达高于对照组,两组比较差异有统计学意义（P〈0．05）。Westernblot显示,γ—GCS与p-PKB在COPD组蛋白表达高于对照组,且差异有统计学意义（P〈0．05）。SPSS10．0直线相关分析得出p-PKB蛋白表达与γ-GCS活性、mRNA及蛋白表达呈正相关。结论COPD大鼠肺组织1．GCS蛋白和mRNA表达增高,p-PKB蛋白也有相应高表达,提示p-PKB和γ-GCS可能在COPD的发病机制中起作用,且PKB可能参与了γ-GCS的信号转导。     

房间隔缺损患者行经封堵术后右心室容量及血浆心钠素的变化

目的:观察房间隔缺损(ASD)封堵术后右心室容量及血浆心钠素(ANP)的变化。方法:对23例成功行经导管ASD封堵术的患者,分别于封堵术前、术后3天取静脉血,采用放射免疫法测定血浆ANP浓度;并于术前、术后3天行心脏三维超声心动图检查,测量右心室腔容量;并对ANP与肺动脉压(PAP)、右心室腔容量、右室射血分数进行相关分析。结果:ASD封堵术后3天血浆ANP浓度较术前明显降低(101.89±35.80ng/Lvs153.46±74.55ng/L,P<0.01);封堵术后3天右心室容量较术前明显缩小,差异有统计学意义(P<0.05),相关分析显示:ASD患者血浆ANP浓度与PAP(r=0.74)、右心室舒张末期容量(r=0.50)、收缩末期容量(r=0.50)分别呈正相关(P均<0.05)、与右室射血分数呈负相关(r=-0.38,P<0.05)。结论:ASD封堵术后血浆心钠素浓度明显降低,右心室腔明显缩小。     

p38 Mitogen-Activated Protein Kinase Inhibition Decreases TNFalpha Secretion and Protects Against Left Ventricular Remodeling in Rats with Myocardial Ischemia

The purpose of this study was to test our hypothesis that p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 may favorably affect tumor necrosis factor alpha (TNFα) secretion and left ventricular (LV) remodeling after myocardial ischemia (MI). The left anterior descending coronary artery (LAD) was ligated to produce anterior MI in 40 rats that were randomly divided into two groups: p38i group (n = 24) and MIR group (MI rat models, n = 24). A sham operation group without LAD ligation (Sham, n = 16) was also studied. SB203580 (2 mg/kg) and saline was injected i.p. once every 3 days in the first two groups, respectively. One and six weeks after MI, cardiac function, myocardial fibrosis, the cardiac expressions of phosphorylated p38 MAPK (p-p38 MAPK), TNFα, alpha smooth muscle actin (αSMA) and collagen I, the ultramicrostructure of the myocardium were examined by echocardiography, histological staining, western blot, immunohistochemical staining, transmission electron microscope (TEM), respectively. Treatments with SB203580 suppressed myocardial fibrosis and LV remodeling, as well as attenuated the expressions of p-p38-MAPK, TNFα, αSMA and collagen I as compared with the MIR. In conclusion, SB203850 has an effect of inhibiting inflammation-induced fibrosis, which leads to attenuation of LV remodeling.     

吗啡长时程作用对小鼠脑组织蛋白激酶A及C活性的影响

本文通过复制小鼠吗啡耐受依赖模型，观察了吗啡长时程作用对小鼠脑组织ＰＫＡ及ＰＫＣ活性的影响。结果发现：（１）吗啡耐受依赖小鼠纹状体、海马、大脑皮层神经细胞胞浆ＰＫＡ活性显著升高，而小脑胞浆及以上各部位膜相ＰＫＡ活性变化不明显；（２）不同脑组织中ＰＫＣ活性变化不同，吗啡耐受依赖小鼠大脑皮层及小脑胞浆ＰＫＣ活性明显升高，在纹状体胞浆则显著下降，但纹状体膜相ＰＫＣ活性却显著增加，海马及小脑膜相ＰＫＣ活性则明显降低；（３）纳洛酮可拮抗吗啡引起的上述变化。结果提示：一些脑组织胞浆ＰＫＡ活性的升高、ＰＫＣ活性的变化以及可能存在的ＰＫＣ于胞浆和膜相之间的移位可能是吗啡耐受依赖的重要生化基础，且此变化可能由阿片受体所介导。     

Brain‐Derived Neurotrophic Factor Enhances Bcl‐xL Expression Through Protein Kinase Casein Kinase 2‐Activated and Nuclear Factor Kappa B‐Mediated Pathway in Rat Hippocampus

Brain‐derived neurotrophic factor (BDNF) was shown to produce its neuroprotective effect through extracellular signal‐regulated kinase 1/2 (ERK1/2) and phosphatidylinositol‐3 kinase (PI3‐K) signaling. But whether other pathways also mediate the neuroprotective effect of BDNF is less known. In this study, we found that direct administration of BDNF to rat hippocampal CA1 area dose‐dependently increased the mRNA and protein levels of Bcl‐xL. BDNF also increased protein kinase casein kinase II (CK2) activity and NF‐κB phosphorylation at Ser529 dose‐dependently. Further, transfection of the wild‐type CK2α DNA to CA1 neurons increased nuclear factor kappa B (NF‐κB) phosphorylation and Bcl‐xL mRNA expression, whereas transfection of CK2α156A, the catalytically inactive mutant of CK2α, decreased these measures. Moreover, transfection of CK2α small interfering RNA (siRNA) blocked the enhancing effect of BDNF on NF‐κB phosphorylation and Bcl‐xL expression. These results were further confirmed by treatment of 4,5,6,7‐tetrabromobenzotriazole (TBB), a specific CK2 inhibitor. Transfection of NF‐κBS529A, the dominant negative mutant of NF‐κB, prevented the enhancing effect of BDNF on Bcl‐xL expression. More importantly, BDNF activation of CK2 is not affected by co‐administration of the ERK1/2 inhibitor, PD98059, and the PI3‐K inhibitor, LY294002. These results demonstrate a novel BDNF signaling pathway and provide an alternative therapeutic strategy for the protective effect of BDNF on hippocampal neurons in vivo.     

Effect of Focal Adhesion Kinase on the Regulation of Realignment and Tenogenic Differentiation of Human Mesenchymal Stem Cells by Mechanical Stretch

Focal adhesion kinase (FAK) is a focal adhesion-associated protein kinase involved in cell adhesion and spreading. It is recruited as a participant in focal adhesion dynamics between cells and has a role in cell motility, differentiation, and survival. The role of FAK in the differentiation of human mesenchymal stem cells (hMSCs), however, is not well understood, particularly in terms of tenogenic differentiation. In this study, we reported that FAK regulates the mechanical stretch-induced realignment of hMSCs. We showed that FAK can be activated by mechanical stretch and, with a 10 μM PF 573228 (a novel small molecule inhibitor of FAK) treatment, FAK autophosphorylation at Tyr397 is significantly decreased. Moreover, our findings demonstrated that this decrease in FAK autophosphorylation at Tyr397 leads to the attenuation of upregulation of mechanical stretch-induced mRNA expression of tendon-related genes, including type I collagen, type III collagen, tenascin-C, and scleraxis. These results indicate that the FAK signaling molecule plays an important role in regulating cell realignment and tenogenic differentiation of hMSCs when induced by mechanical stretch. Collectively, our findings provide novel insight into the role of FAK in the realignment and mechanotransduction of hMSCs during the process of tenogenic differentiation induced by mechanical stretch.     

卡托普利对SHR心肌VEGF表达及微血管的影响

目的检测卡托普利降压治疗前后自发性高血压(SHR)心肌血管内皮生长因子(VEGF)表达水平与微血管密度的变化,探讨该药物是否具有逆转微血管稀少的作用。方法60只8月龄大鼠均分成正常血压对照组(WKY),SHR组和卡托普利治疗SHR组,用单宁酸-氯化铁组织化学法检测心肌微血管,用免疫组化SP法检测心肌VEGF蛋白表达,并对上述3组心脏切片用计算机图象分析系统进行定量观察分析。结果对照组SHR心肌微血管密度比对照组WKY减少,而VEGF表达水平比WKY组增强(均P<0.05),卡托普利治疗组SHR心肌微血管密度增加,而VEGF表达水平下降,与对照组SHR比较差异具有显著性(P<0.05),而与WKY组相当(P>0.05)。结论卡托普利在降压治疗的同时可下调VEGF表达水平,并逆转微血管减少,从而对靶器官具有保护作用。     

豚鼠哮喘模型核因子-κB的表达特点及灯盏花素对其作用的研究

目的:探讨核因子-κB(NF-κB)在豚鼠哮喘模型中的表达特点以及蛋白激酶C(PKC)抑制剂灯盏花素对其表达的影响。方法:将48只豚鼠随机分为正常对照组、哮喘即刻激发组、哮喘发作1周组、哮喘发作2周组、灯盏花素治疗1周组和治疗2周组等6组,每组8只,测定肺功能并观察气道壁嗜酸性粒细胞(EOS)浸润情况;用免疫组织化学染色方法观察NF-κB在豚鼠肺组织中的表达变化。结果:NF-κB主要表达于气道上皮细胞,哮喘各组NF-κB的表达水平均显著高于正常对照组(P＜0101),治疗2周组NF-κB的表达水平显著低于哮喘各组(P＜0.01)。NF-κB的表达水平与气道阻力及气道壁EOS计数均呈显著正相关(P＜0101)。结论:哮喘豚鼠气道上皮细胞NF-κB的表达水平显著高于正常豚鼠,提示NF-κB可能参与哮喘的发病过程;PKC抑制剂灯盏花素能显著降低哮喘豚鼠气道上皮细胞NF-κB的表达水平,提示PKC可能通过NF-κB的作用参与哮喘的发病机制。     

Atrial natriuretic peptide effects on cGMP and cAMP contents in microdissected glomeruli and segments of the rat and rabbit nephrons

A microradioimmunoassay has been developed in order to measure the changes in cGMP cell content induced in vitro by atrial natriuretic peptides (ANP) in either glomeruli or defined portions of tubules microdissected from collagenase treated rat and rabbit kidneys. When tested at 0.1 M or 1 M, all ANP analogues used produced in rat glomeruli a 20–25 fold increase in cGMP accumulation compared to basal values. Threshold responses were obtained with about 1 nM ANP and apparentK _a values ranged between 5 and 50 nM. Atriopeptin III led to similar results in glomeruli isolated from rabbit. Under the same experimental conditions, no cGMP could be detected in any ANP-treated nephron segment from the rat kidney (namely, from the proximal convoluted tubule up to the outer medullary collecting tubule) nor in cortical collecting tubules isolated from the rabbit kidney. Moreover, ANP did not after the forskolin-induced increase in cAMP content in glomeruli or collecting tubules, nor the AVP-induced increase in cAMP content in collecting tubules. Our data confirm the marked effect of ANP on cGMP generation by isolated glomeruli from rat and rabbit; however, they are not competible with a direct action of ANP stimulating cGMP generation in tubules or inhibiting vasopressin-induced cAMP generation in collecting tubules.     

核因子κB在蛋白激酶C诱导哮喘模型大鼠气道平滑肌细胞增殖中的作用

目的:探讨核因子κB(NF-κB)在蛋白激酶C(PKC)致哮喘模型大鼠气道平滑肌细胞(ASMCs)增殖中的作用。方法:16只Wistar大鼠随机分为哮喘组(8只)和对照组(8只)。应用PKC激动剂PMA和NF-κB抑制剂PDTC干预哮喘组和对照组大鼠ASMCs。采用流式细胞术、MTT法及增殖细胞核抗原(PCNA)免疫荧光技术等方法检测ASMCs增殖;免疫荧光技术及电泳迁移率改变分析(EMSA)检测NF-κB活性。结果:PMA干预哮喘组ASMCs后S期细胞比例、A值、PCNA表达率、NF-κBp65阳性率及结合带的灰度值均显著高于未干预的哮喘组ASMCs(均P<0.05),PDTC预处理后再给予PMA上述指标均低于仅用PMA干预及未干预者(均P<0.05)。仅用PDTC处理的哮喘组ASMCs上述指标均低于未干预的ASMCs(均P<0.05)。结论:NF-κB参与哮喘大鼠ASMCs增殖,在其增殖中存在着PKC-NF-κB信号途径。