间歇有氧运动上调自发性高血压大鼠血管肾上腺髓质素

目的研究间歇有氧运动(IAE)对自发性高血压大鼠(SHR)主动脉肾上腺髓质素(ADM)的影响,探讨运动降低血压的大血管因素及其机制。方法 SHR 30只,随机分为间歇有氧运动组(IAE组)和对照组。IAE组进行8周间歇跑台有氧运动。采用尾压法测血压,酶联免疫吸附法(ELISA)测运动前后血清中ADM的含量,免疫组织化学法显示SHR主动脉ADM的表达,蛋白质印迹实验检测主动脉ADM的特异性受体——受体活性修饰蛋白2(RAMP2)和降钙素受体样受体(CRLR)定量水平。结果 IAE组血压明显低于对照组(P0.05);IAE组血清中ADM的含量明显高于对照组(P0.05);主动脉ADM表达明显强于对照组(P0.05);主动脉RAMP2和CRLR定量均明显高于对照组(P0.05)。结论间歇有氧运动可能通过增强血管ADM及其特异性受体表达使SHR大鼠血压下降。     

褪黑素在有氧运动改善自发性高血压大鼠血压和肠系膜动脉功能中的作用

目的探讨褪黑素在有氧运动改善自发性高血压大鼠(SHR)血压和肠系膜动脉功能中的作用。方法选用12周龄雄性SHR 54只和Wistar-Kyoto(WKY)大鼠(WKY组,即正常血压对照组)18只。SHR随机分为5个组,即安静空白对照组(SHR-SED组,n=18)、安静生理盐水注射组(SHR-SED+NS组,n=6)、安静褪黑素受体阻断剂2-苯基-N-乙酰色胺(Luz)[1 mg/(kg·d)]注射组(SHR-SED+Luz组,n=6)、有氧运动组(SHR-EX组,n=18)、有氧运动Luz注射组(SHR-EX+Luz组,n=6)。运动组进行8周有氧训练:坡度0°,18~20 m/min,每天60min,每周5天。8周有氧运动后,采用尾动脉无创法测量大鼠血压与心率;WKY组、SHR-SED组、SHR-EX组采用ELISA竞争法测定血清褪黑素水平;离体微血管环实验测定二、三级肠系膜动脉的舒缩特性。结果 (1)8周有氧运动后,SHR-EX组的收缩压、舒张压、平均动脉压和心率与SHR-SED组相比显著降低。SHR-EX+Luz组的收缩压、心率明显高于SHR-EX组,却低于SHR-SED+Luz组;而SHR-SED组与SHR-SED+NS组、SHR-SED+Luz组比较无差异。(2)WKY组和SHR-SED组血清褪黑素浓度在21∶00~22∶00时最高,明显高于12∶00~13∶00和8∶00~9∶00;但SHR-EX组在8∶00~9∶00最高。在3个时间段内,WKY组血清褪黑素浓度始终显著高于SHR-SED组;但在8∶00~9∶00时间段,SHR-EX组明显高于WKY组、SHR-SED组。(3)微血管环在去甲肾上腺素(10-5mol/L)预收缩后,对褪黑素(10-6~10-3mol/L)呈浓度依赖性舒张反应,p IC50值:WKY组SHR-EX组SHR-SED组,且各组无Nω-硝基-L-精氨酸甲酯的内皮完整血管舒张幅度大于有Nω-硝基-L-精氨酸甲酯(10-4mol/L)的内皮不完整血管;Luz(2×10-6mol/L)预孵育微血管环20 min,可部分阻断褪黑素的舒张作用。结论有氧运动可降低SHR的收缩压和心率,增强肠系膜动脉舒张作用,其中褪黑素发挥了重要作用。     

盐酸埃他卡林对自发性高血压大鼠血浆生化指标及炎症相关因子的影响

目的观察盐酸埃他卡林(Ipt)对自发性高血压大鼠血浆生化指标及炎症相关因子的影响。方法SHR大鼠在2月龄进入实验,体重200～250g,雌雄不限,随机分为6组:SHR对照组5只,WKY对照组5只,Ipt 3个剂量1、3、9mg·kg~(-1)·d~(-1)治疗组各6只,苯那普利(Ben)6mg·kg~(-1)·d~(-1)治疗组6只。灌胃给药每天1次,8wk后处死动物,检测血浆Glu,Tcho,TG,LDL-c,HDL-c, BUN,Cr,UA,Ins,hs-CRP,IL-6,TNF-α等指标。结果SHR大鼠对照组较WKY大鼠对照组,血浆BUN,Cr,UA显著增高(P＜0．05),血糖、血脂无显著差异(P＞0．05),经Ipt 1、3、9mg·kg~(-1)·d~(-1)及Ben 6mg·kg~(-1)·d~(-1)治疗后,血浆BUN,Cr,UA降至正常;SHR大鼠与WKY大鼠对照组比较,血浆Ins、hs-CRP、TNF-α、IL-6显著增高,Ipt 3、9mg·kg~(-1)·d~(-1)剂量治疗后,较SHR对照组大鼠均显著降低(P＜0．05),1mg·kg~(-1)·d~(-1)剂量及Ben治疗后,无明显改变(P＞0．05)。结论盐酸埃他卡林及苯那普利均能有效地改善肾功能,盐酸埃他卡林3、9mg·kg~(-1)·d~(-1)剂量治疗后能降低血浆Ins、TNF-α、IL-6、hs-CRP等炎症相关因子。     

依普利酮对自发性高血压大鼠心肌纤维化的影响及其机制探讨

目的：观察依普利酮对自发性高血压（ SHR）大鼠心肌纤维化（ MF）的影响,并探讨其机制。方法雄性SHR大鼠28只,随机分为4组,即依普利酮组、替米沙坦组、联合组及对照组,每组7只。分别灌胃给予依普利酮100 mg／（kg· d）、替米沙坦10 mg／（kg· d）、替米沙坦10 mg／（kg· d）＋依普利酮100 mg／（kg· d）、生理盐水1 mL／d,用药共8周。给药前、给药2周及7周应用尾套法测定尾动脉收缩压,给药8周免疫组化法测定心肌组织中的骨形态发生蛋白7（BMP-7）、转化生长因子信号蛋白2（Smad2）。结果给药7周,依普利酮组、替米沙坦组、联合组尾动脉收缩压均低于对照组（P均＜0．05）。联合组、依普利酮组左心室质量指数均低于对照组,依普利酮组低于联合组,P＜0．05。依普利酮组心肌组织Smad2阳性表达低于对照组,依普利酮组及联合组BMP-7阳性表达高于对照组,P均＜0．05。结论依普利酮可抑制SHR大鼠MF,促进BMP-7表达、抑制Smad2表达可能是其作用机制之一。     

有氧运动对自发性高血压大鼠骨骼肌毛细血管稀疏的影响

目的探讨有氧运动对于自发性高血压大鼠(SHR)毛细血管稀疏是否有改善作用以及其作用机制是否与血管内皮生长因子(VEGF)的表达改变有关。方法 3月龄雄性WKY和SHR随机分为WKY安静组(WKYSED)、WKY运动组(WKY-EX)、SHR安静组(SHR-SED)、SHR运动组(SHR-EX),每组各12只。WKY-SED组和SHR-SED组不进行运动干预,WKY-EX组和SHR-EX组进行12周跑台运动(20 m/min,60 min/d,5 d/w,坡度为0,相当于55%~65%VO2max)。Western blot测定VEGF蛋白在大鼠腓肠肌中的表达,免疫组织化学观测VEGF在大鼠腓肠肌中的分布变化,HE染色观察各组大鼠腓肠肌石蜡切片中毛细血管的数量。结果免疫组织化学检测结果表明SHR-SED组VEGF在大鼠腓肠肌中的分布显著低于WKY-SED组(P0.01),12周有氧运动后,SHR-EX组VEGF在大鼠腓肠肌中的分布显著高于SHR-SED组(P0.01)。Western blot结果发现SHR-SED组的VEGF表达量与WKY-SED组差异不显著(P0.05),12周有氧运动后,SHR-EX组的VEGF表达量显著高于SHR-SED组(P0.05)。HE染色结果发现SHR-SED组的毛细血管与肌纤维数比值(C/F)显著低于WKY-SED组(P0.01),12周有氧运动之后,SHR-EX组的C/F值显著高于SHR-SED组(P0.01)。结论:微血管稀疏是导致高血压的原因之一,有氧运动可以促进VEGF的表达并且促进毛细血管新生。     

心脏肥大细胞在自发性高血压大鼠心肌重构中的作用

目的探讨心脏肥大细胞在自发性高血压大鼠(SHR)心肌重构中的作用。方法应用病理检查、计算机分析结合逆转录聚合酶链式反应等方法,观察SHR及Wistar-Kyoto大鼠(WKY)收缩压、左室重量指数、心肌细胞直径、肥大细胞密度、心肌胶原容积分数(CVF)、心肌血管周围胶原面积比(PV-CA)和心肌Ⅰ、Ⅲ型胶原mRNA表达水平的变化。肥大细胞密度与左室重量指数、CVF及PVCA之间的关系采用相关分析。结果与WKY比较,SHR收缩压为(206±18)比(108±10)mm Hg(P<0.01);SHR组左室重量指数为(4.6±0.4)比(3.3±0.3)mg/g,(P<0.01);SHR组心肌细胞长径为(17.4±1.9)比(10.0±2.2)μm(P<0.01);SHR组心肌细胞短径为(9.0±2.0)比(5.8±1.7)μm(P<0.01);SHR组肥大细胞密度为(7.4±3.2)比(1.9±1.2)个/mm2(P<0.01),SHR组肥大细胞密度为WKY组的3.9倍。SHR组CVF、PVCA分别为46.4%±7.8%和1.9±0.9,WKY组分别为24.4%±10.7%和0.4±0.1,SHR组明显升高(P<0.01)。SHR组心肌Ⅰ、Ⅲ型胶原mRNA表达相对含量也均明显高于WKY(P<0.01),心脏肥大细胞密度与左室重量指数、CVF及PVCA存在明显的正相关(相关系数分别为0.67、0.87和0.95,P<0.01)。结论心脏肥大细胞密度增加可能是促进SHR心肌重构的重要原因。     

通心络对自发性高血压大鼠血管内皮功能的影响

目的 观察通心络胶囊对自发性高血压大鼠(SHR)血管内皮功能的保护作用.方法 将24只SHR随机分为通心络组(TXL组)、咪达普利组(MD组)和生理盐水组(SHR组),每组8只.同时还有8只同龄Wistar-Kyoto(WKY)大鼠作为正常对照组.TXL组和MD组分别以通心络胶囊280 mg/(kg·d)和咪达普利0.90 mg/(kg·d)配成2 mL水溶液灌胃4周.SHR组与WKY组灌胃等量生理盐水.实验结束后取血测定内皮素-1(ET-1)、一氧化氮(NO)、血管紧张素Ⅱ(AngⅡ)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性.结果 SHR组NO浓度与SOD活性均低于WKY组(P<0.01),TXL组NO浓度与SOD活性则高于SHR组(P<0.01),SHR组ET-1、AngⅡ及MDA水平高于WKY组(P<0.01),TXL组ET-1、AngⅡ及MDA水平均低于SHR组,与MD组比较则无统计学意义(P>0.05).结论 通心络胶囊可能通过增加NO浓度和SOD活性,降低ET-1、AngⅡ及MDA水平,对血管内皮具有保护作用.     

罗格列酮对自发性高血压大鼠心脏保护作用的形态学研究

目的　探讨自发性高血压大鼠 (SHR大鼠 )心脏形态学的改变及罗格列酮对SHR大鼠心脏的保护作用。方法　SHR大鼠 2 4只 ,随机分成两组。实验期 8w ,取组织标本 ,采用光镜和电镜观察大鼠心肌结构的改变。结果　SHR大鼠心肌间质出现胶原纤维的增殖 ,心肌细胞的结构也发生了改变 ,经罗格列酮治疗后 ,大鼠心肌间质胶原含量明显减少 ,心肌细胞形态得到明显改善。结论　罗格列酮对逆转高血压所致的心肌重构具有一定的作用     

雌激素对自发性高血压大鼠心肾纤维化的影响

为探讨雌激素对自发性高血压大鼠心肾纤维化的影响 ,将雌性自发性高血压大鼠随机分为假手术、去卵巢雌激素治疗组和去卵巢安慰剂组。分别测量治疗前后大鼠血压和体重 ,3个月后测左心室重和血清雌二醇水平 ,采用免疫组织化学方法及计算机图像分析仪检测转化生长因子 β1 在心脏及肾脏的表达 ,采用苦味酸天狼星红染色及计算机图像分析仪检测心肌间质胶原容积分数。结果发现 ,去卵巢雌激素治疗组血压和转化生长因子 β1 在心、肾的表达和左心室重 体重以及心肌间质胶原容积分数等明显低于去卵巢安慰剂组 (P <0 .0 5 ) ,与假手术组无明显差别 ;去卵巢安慰剂组上述指标均高于假手术组 (P <0 .0 5 )。以上提示 ,自发性高血压大鼠去卵巢后血压升高 ,雌激素替代治疗后能抑制其血压升高 ,抑制其心肾纤维化。     

葫芦巴碱对脑梗死大鼠认知障碍及氧化应激损伤的影响

目的 基于沉默信息调节因子1(Sirt1)/叉头框蛋白O1(FoxO1)通路探究葫芦巴碱对脑梗死大鼠认知障碍及氧化应激损伤的影响。方法 90只SD大鼠,随机选取18只大鼠为假手术组,其余大鼠采用线栓法建立脑梗死模型,造模后分为模型组、葫芦巴碱低剂量(低剂量)组(葫芦巴碱50 mg/kg)、葫芦巴碱高剂量(高剂量)组(葫芦巴碱100 mg/kg)、葫芦巴碱+EX-527组(100 mg/kg葫芦巴碱+5 mg/kg Sirt1特异性抑制剂EX-527),每组18只;另取18只大鼠为假手术组。采用生化法检测脑组织丙二醛含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性;Western blot检测Sirt1、FoxO1、乙酰化FoxO1(Ac-FoxO1)蛋白表达。结果 与假手术组比较,模型组逃避潜伏期、神经功能缺损评分、海马神经元凋亡指数、活性氧阳性细胞数、丙二醛、Ac-FoxO1蛋白水平明显升高,在目标象限中的时间、穿越平台次数、SOD和GSH-Px活性以及Sirt1、FoxO1蛋白水平明显降低(P<0.05);与模型组比较,低剂量组和高剂量组神经功能缺损评分...     

糜酶抑制剂对自发性高血压大鼠心肌纤维化的影响

目的观察心脏糜酶在自发性高血压大鼠（SHR）心肌组织胶原合成和心肌纤维化中的作用。方法应用病理检查、计算机分析结合逆转录-聚合酶链式反应等方法,检测SHR应用糜酶抑制剂组（ChyI组）、SHR组及对照正常血压大鼠WistarKyoto组（WKY组）收缩压、心肌胶原容积分数（CVF）、心肌血管周围胶原面积比（PVCA）和心肌糜酶及I、III型胶原mRNA表达。结果ChyI组心脏CVF、PVCA分别为（27±9）%和0.4±0.1,SHR组分别为（46±8）%和1.9±0.9,WKY组为（24±11）%和0.4±0.1,ChyI组比SHR组显著下降（P<0.01）,与WKY组无显著差异。ChyI组心肌组织I、III型胶原和糜酶mRNA表达相对含量均显著低于SHR组（P<0.01）,与WKY组无显著差异。应用ChyI后大鼠血压与SHR比较,无显著改变。结论心肌组织糜酶参与胶原的合成,参与细胞外基质的形成和降解,促进SHR心肌纤维化,糜酶抑制剂可能对改善心肌纤维化有益。     

Effect of farnesyltransferase inhibition on cardiac remodeling in spontaneously hypertensive rats

Background

Farnesyltransferase (FT), an essential enzyme at the downstream of mevalonate pathway, was reported to be upregulated in hypertrophic cardiomyocytes of spontaneously hypertensive rats (SHRs) compared with myocardium of Wistar-Kyoto rats (WKYs). This upregulation was accompanied with cardiac remodeling. This study was designed to determine whether FT inhibition can alter cardiac remodeling in SHRs.

Methods

Twelve-week-old SHRs were randomized to receive infusion of either NS or FTI-276 (307 μg/kg/d i.v. each n = 10). WKY rats served as normal controls (n = 6). Echocardiography was performed before and after intervention. SHR hearts were perfused ex vivo for the evaluation of cardiac performance, collagen deposition and biochemical changes (activation of Ras, extracellular-signal regulated kinases/ERK1/2, procollagen type ?/Ш, TGF-β1, connective tissue growth factor/CTGF, and bone morphogenetic protein-7/BMP-7 expression).

Results

FTI-276 intervention decreased interventricular septum wall thickness at end- diastole (IVSd) and relative wall thickness (RWT) of SHRs (P< 0.05). Three week intervention with FTI-276 attenuated hydroxyproline content (P < 0.05), collagen deposition (P < 0.01), Ras activation, ERK1/2 phosphorylation (P < 0.01) and mRNA expression of procollagen type I, TGF-β1 and CTGF and elevated mRNA expression of BMP-7 (P < 0.05) in left ventricle of SHRs.

Conclusion

The present study indicated that FT inhibition could attenuate myocardial fibrosis and partly improve cardiac remodeling in SHRs. The beneficial effects might be mediated through suppression of the activation of Ras and ERK1/2 phosphorylation pathway. The enhanced mRNA expression of BMP-7 with inhibition of TGF-β1 and CTGF mRNA expression might be an important mechanism.     

有氧运动抑制老年高血压大鼠血管功能重塑的氧化应激机制

目的研究有氧运动对老年自发性高血压大鼠(SHR)内皮功能的影响,探讨氧化应激在其中的作用机制。方法实验选用24只16月龄雄性SHR大鼠,随机分为高血压安静组(SHR-C,n=12)、高血压运动组(SHREX,n=12);选用24只同龄雄性正常血压大鼠(WKY),随机分为正常血压安静组(WKY-C,n=12)、正常血压运动组(WKY-EX,n=12)。运动组以16~18 m/min进行8周跑台运动(0°slope,5 d/w,60 min/d),安静组不进行任何运动干预。8周训练末进行血压测定、离体肠系膜动脉张力测定、氧化应激相关指标和一氧化氮(NO)含量检测。结果SHR-EX组收缩压显著低于SHR-C组(P0.05),而WKY-EX组收缩压与WKY-C组无显著性差异(P0.05)。SHR-C组血清丙二醛(MDA)含量(11.8±1.0μmol/L)显著高于WKY-C组(7.2±0.3μmol/L,P0.05),而SHR-EX组血清丙二醛(MDA)含量(7.9±0.3μmol/L)显著低于SHR-C组(P0.05);各组间主要的抗氧化物酶谷胱甘肽过氧化物酶和过氧化物歧化酶没有显著差异(P0.05)。SHR-C组NE诱发的血管收缩反应(153.2±1.9%KMAX)显著高于WKY-C组(120.2±5.6%KMAX,P0.05),SHR-EX组NE诱发的血管收缩反应(136.0±1.8%KMAX)显著低于SHRC组(P0.05),但WKY-EX组NE诱发的血管收缩反应(143.9±4.3%KMAX)仍显著高于WKY-C组(P0.05);SHRC组内皮依赖性血管舒张(50.2±2.8%NE)显著小于WKY-C组(100.1±0.6%NE,P0.05),SHR-EX组内皮依赖性血管舒张(97.0±1.5%NE)显著高于SHR-C组(P0.05)。离体微血管环加入NADPH氧化酶抑制剂Apocynin预孵育15 min后,SHR-C组血管内皮最大舒张(98.6±1.3%NE)显著增高(P0.05)。SHR-C组NO依赖性血管舒张(25.5%±2.3%)显著低于WKY-C组(85.2%±0.7%,P0.01),SHR-EX组和WKY-EX组NO依赖性血管舒张(86.8%±3.4%和98.8%±1.5%)显著高于对应的安静组(P0.05)。结论长期有氧运动抑制由衰老和/或高血压诱导的氧化应激水平增高、NO生物利用度降低,进而改善血管内皮功能障碍。     

Impact of swimming exercise on inflammation in medullary areas of sympathetic outflow control in spontaneously hypertensive rats

Metabolic Brain Disease - Exercise reduces sympathetic activity (SA), arterial pressure and heart rate in spontaneously hypertensive rats (SHR). Exercise increases oxidative stress (OS) and...     

Effects of exercise on hypocholesterolemia of stroke-prone spontaneously hypertensive rats

The effects of exercise on hypocholesterolemia, one of the risk factors of cerebrovascular disorders, were examined. 47-51-day-old stroke-prone spontaneously hypertensive rats (stroke-prone SHRs) were assigned to 2 groups, sedentary or exercise, and raised for 8 weeks. The total serum cholesterol level of the exercised group was 17-18% higher (P less than 0.01) than the control group, and the level of cholesterol synthesis in the liver of the former group significantly higher than in the latter. On the other hand, the level of intestinal cholesterol synthesis in the exercised group was significantly lower. The activity of HMG-CoA reductase in the liver microsomes was significantly increased by exercise, but the activity of this enzyme in the small intestine was not affected. A significant correlation was observed between the rate of cholesterol synthesis in the liver and the amount of radiolabeled cholesterol released into the serum. From these results, we conclude that the enhancement of the synthesis and the release of cholesterol in the liver by exercise is a major cause of the exercise-induced increase in serum cholesterol of stroke-prone SHRs.     

盐酸埃他卡林对脑卒中易感型自发性高血压大鼠心功能的影响

目的研究盐酸埃他卡林（Ipt）对大鼠无创心功能参数的影响。方法利用清醒无创心功能血流动力学计算机监测系统,对比研究Ipt对正常血压大鼠和脑卒中易感型自发性高血压大鼠（SHRsp）心率、心脏收缩、舒张和泵血功能的影响。结果Ipt0.5mg/kg静注可降低SHRsp心率、室缩波、抑制心肌收缩力指数,延长左室射血期和心肌电机械收缩时间,降低心输出量,延长左室舒张期。Ipt相同剂量对正常血压大鼠心功能参数却无明显影响。结论Ipt可抑制SHRsp大鼠心脏收缩和泵血功能,延长左室舒张期时间,但不影响正常血压大鼠心脏功能,提示Ipt对心功能的影响与血压状态密切相关。     

运动对心脏的保护作用及其机制的研究进展

运动训练有益心脏健康,可以改善心血管疾病患者的运动能力和生活质量,降低其致死率和致残率。尽管运动的益处显而易见,但是运动训练对于心脏疾病的保护机制尚不明确。本文重点综述了运动保护心脏的主要机制,以及运动对于心肌梗死、缺血再灌注损伤、病理性心肌肥厚、心脏衰老等心脏疾病的保护作用及最新研究进展,以期从"运动"这一独特视角,为心脏疾病的防治提供新思路和新策略。     

Microvascular cell death in spontaneously hypertensive rats during experimental inflammation

OBJECTIVE: Chronic hypertension is associated with an increased risk for tissue injury that may be mediated in part by endothelium and inflammatory cells. To clarify a possible underlying mechanisms, we examined leukocyte migration in the microcirculation and concomitant parenchymal cell death. METHODS: The mesentery of spontaneously hypertensive rats (SHRs) and their normotensive controls, Wistar Kyoto (WKY) rats, was examined with digital fluorescence microscopy after topical stimulation with an inflammatory mediator (f-met-leu-phe, 10(-8)M). The migratory pathways of individual leukocytes were traced, and at the same time cell death was detected by use of a life-death indicator (propidium iodide) over a period of 3 hours. RESULTS: Both WKY and SHR had a progressively increasing number of leukocytes migrating across the endothelium in postcapillary venules into the tissue parenchyma. But parenchymal cell death was detected in a random pattern in the mesentery tissue, without correlation to the migratory positions of the leukocytes. Although mature SHR rats (about 17 weeks) exhibited the same level of cell death as age-matched WKY rats, older WKY rats (about 30 weeks) had significantly lower levels of cell death, whereas the SHR rats maintained the same number of parenchymal cell death as mature animals. CONCLUSIONS: These results suggest that in the presence of an inflammatory mediator, the SHR may exhibit a stronger response to an inflammatory mediator than normotensive WKY rats in a fashion that is age, but not blood pressure, dependent. Parenchymal cell death does not correlate with migration of activated leukocytes at the microvascular level.