缬沙坦对自发性高血压大鼠脑超微结构和 Klotho基因表达的影响

目的：探讨缬沙坦对自发性高血压模型鼠脑超微结构及其脑组织中Klotho基因和微炎症因子（ICAM-1和VCAM-1）表达的影响。方法：选取22周龄雄性自发性高血压模型鼠10只,随机分为高血压组与缬沙坦组（5只/组）,Wistar-kyoto大鼠（WKY）5只作为正常对照组。通过电镜观察各组大鼠脑的超微结构,RT-PCR、免疫组织化学技术和Western印迹检测Klotho基因和微炎症因子（ICAM-1和VCAM-1）的表达。结果：高血压组大鼠脑神经元细胞的超微结构主要表现为细胞固缩、染色质边集、典型凋亡小体形成,但经过缬沙坦干预后,其神经元损害有所减轻。RT-PCR结果显示缬沙坦干预能够上调Klotho mRNA表达水平、下调微炎症因子ICAM-1和VCAM-1 mRNA的表达;免疫组织化学技术和Western印迹检测证实缬沙坦干预能够增加Klotho蛋白、减少ICAM-1和VCAM-1蛋白的表达。结论：缬沙坦能够上调Klotho的表达,改善高血压脑超微结构的改变。     

自发性高血压大鼠和Wistar大鼠脑动脉Cx45表达的差异

目的 探讨脑动脉细胞间缝隙连接在高血压病中的变化。方法 应用全细胞膜片钳、定量RT PCR和Western blot技术,比较自发性高血压(SH)大鼠(n=30)和Wistar大鼠(n=30)脑动脉上缝隙连接耦联力,以及连接蛋白45(Cx45)在mRNA和蛋白水平的表达。结果 ① 应用全细胞膜片钳技术发现,SH大鼠脑动脉平滑肌细胞膜电容和膜电导都明显高于正常Wistar大鼠(P<0.05),提示SH大鼠脑动脉平滑肌细胞间的缝隙连接耦联力增强。② 应用定量RT PCR技术发现,SH大鼠脑动脉Cx45 mRNA的表达升高(P<0.05)。③ 应用Western blot发现,SH大鼠脑动脉Cx45的蛋白表达升高(P<0.01)。结论 SH大鼠可能通过上调平滑肌细胞上Cx45的表达,增强脑动脉平滑肌细胞间缝隙连接通讯,保证血管的同步收缩。     

心钠素对高血压大鼠动脉平滑肌细胞离子泵活性和基因表达的影响

目的 探讨心钠素(ANP)对自发性高血压大鼠(SHR)动脉平滑肌细胞膜(ASMC)Na+,K+-ATP酶、Ca2+-ATP酶活性及Na+,K+-ATP酶α,亚单位、Ca+-ATP)酶亚型1(PMCA1)mRNA表达的影响.方法 对SHR大鼠,予不同浓度ANP和血管紧张素Ⅱ(Ang Ⅱ)干预,通过放射免疫、生化酶学和逆转录-聚合酶链反应等方法,检测ASMC的ANP、AngⅡ含量,ATP酶活性及其mRNA表达变化并设WKY大鼠为对照.结果 SHR大鼠ANP含量比WKY大鼠下降[(7.3±2.4)pg·10-6比(19.3±3.3) Pg·10-6,P＜0.01],Ang Ⅱ含量增加[(57±4)pg·10-6比(44±4) pg·10-6,P＜0.01],Na+,K+-ATP酶、Ca2+-A11)酶活性及Na+,K+-ATP酶α1亚单位、PMCA1 mRNA表达均显著降低[Na+,K+-ATP:(4.3±0.8) μmol·h-1·mg-1比(5.3±1.0) μmol·h-1·mg-1,Ca2+-ATP酶:(3.2±0.7)μmol·h-1·mg-1比(4.5±0.7) μmol·h-1·mg-1,α1亚单位:0.524±0.025比0.704±0.116,PMCA1:0.193±0.030比0.547±0.045](P＜0.05～P＜0.01).ANP可增加SHR大鼠Na+,K+-ATP酶、Ca2+-ATP酶活性及Na+,K+-ATP酶α1,亚单位及PMCA1 mRNA表达(均P＜0.01),Ang Ⅱ则抑制Ca2+-ATP酶活性和PMCA1 mRNA表达(P＜0.05～P＜0.01),仅1×10-7 mol/L AngⅡ抑制Na+,K+-ATP酶活性及α1亚单位mRNA表达,ANP能拮抗AngⅡ对两种ATP酶活性及其mRNA表达的效应.ANP也能拮抗AngⅡ对WKY大鼠Ca2+-ATP酶活性及PMCA1mRNA表达的效应,对Na+,K+-ATP酶活性及α1亚单位mRNA表达无影响(P＞0.05).结论 高血压大鼠ASMC两种ATP酶活性和基因表达下降与局部ANP和AngⅡ分泌异常有关,ANP能拮抗AngⅡ对两种ATP酶活性和基因表达的效应.     

高血压大鼠肾内一氧化氮合酶活性

目的　观察自发性高血压大鼠肾脏内一氧化氮合酶(NOS)活性变化 ,以探讨高血压病的发病机制 .方法　采用 3H-精氨酸转变成 3H-胍氨酸方法测定 NOS活性 .结果　自发性高血压大鼠 (SHR)肾蛋白内神经型 NOS(n NOS)活性(2 1.9± 7.4) k Bq· g- 1明显低于 Wistar Kyoto(WKY)大鼠(4 .32± 9.3) k Bq·g- 1 ,P<0 .0 5 .在乙酰胆碱 (Ach)刺激后 ,SHR肾内内皮型 NOS(e NOS)活性为 (6 7.3± 14.6 ) k Bq·g- 1 ,而 WKY肾内 e NOS则为 (85 .7± 2 3.8) k Bq· g- 1 ,SHR也显著低于 WKY(P<0 .0 5 ) .结论　n NOS和 e NOS活性不足在高血压病的发生和发展过程中可能起一定作用     

牛磺酸对高血压大鼠中枢神经系统内皮素和降钙素基因相关肽的影响

目的：研究牛磺酸对高血压大鼠中枢神经系统内皮素(ET)和降钙素基因相关肽(CGRP)的影响。方法：16只高血压大鼠(SHR)分为2组，1组术前饲喂牛磺酸2周，另1组饲喂常规饲料。16只正常大鼠同法分组饲喂作对照。分别测定大脑皮质、丘脑和延髓ET-1，CGRP和牛磺酸含量。结果：与正常大鼠相比，SHR大鼠大脑皮质、丘脑和延髓CGRP显著升高，丘脑和延髓ET显著升高。应用牛磺酸治疗后，SHR大鼠大脑皮质、丘脑和延髓CGRP均显著下降，丘脑和延髓ET、牛磺酸显著升高。牛磺酸对正常大鼠脑组织ET和CGRP无显著影响。结论；牛磺酸调节血压机制可能与其影响中枢神经系统ET和CGRP水平有关。     

Superoxide dismutase activity of the salicylate-iron complex.

BACKGROUND: Scavenging of superoxide radical by salicylate-iron complex was studied to determine whether or not the salicylate-iron complex was able to catalyze the dismutation of superoxide radicals, the result perhaps yielding an explanation of the antioxidant and anti-inflammatory properties of the drug. METHODS: The scavenging was studied with an assay that generates O2.- without the intervention of metal ions. RESULTS: Results indicated that, in the presence of iron, salicylate was able to bring about the catalytic dismutation of the superoxide radical. The rate of superoxide removal was dependent on both the concentration of iron and the salicylate:iron molar ratio. CONCLUSIONS: These results may help to explain the interaction of nonsteroidal anti-inflammatory drugs with free radicals and the anti-inflammatory properties of these agents, inasmuch as accumulating evidence indicates that much of the injury observed during inflammatory disorders may be mediated by oxidative stress frequently induced by iron-dependent reactions.     

Tong-xin-luo capsule inhibits left ventricular remodeling in spontaneously hypertensive rats by enhancing PPAR-γ expression and suppressing NF-κB activity

Background Tong-xin-luo capsule （TXL）, used as a traditional Chinese herb, offeres a therapeutic potential for treatment of cardiovascular diseases. It has been shown to exert a variety of pharmacological effects, including antihypertensive effects, and is able to improve ventricular remodeling. However, the mechanisms of its action are not completely understood. The aim of this study was to evaluate the molecular mechanisms of Tong-xin-luo capsule on left ventricular remodeling in spontaneously hypertensive rats （SHR）.
Methods Sixteen eight-week-old SHRs were randomized into an SHR group （n=8） and a TXL group （n=8） that were given Tong-xin-luo capsule （1.5 mg·kg^-1·d^-1）. Eight Wistar Kyoto （WKY） rats fed with 0.9% NaCl served as the control group （WKY group）. Systolic blood pressure （BP）, body weight and heart rate were monitored once every two weeks. Ventricular remodeling was detected by histopathological examination. Nuclear factor kappa B P65 （NF-κB P65） and peroxisome proliferators activated receptor y （PPAR-γ） protein and phosphorylated inhibitor kappa a （IκBα） protein were detected by immunohistochemistry and western blot respectively. The physical interaction of the P65-P50 heterodimer with IκBα and NF-κB were measured by co-immunoprecipitation. PPAR-γ mRNA, collagen Ⅰ mRNA and collagen Ⅲ mHNA were measured by real-time PCR.
Results TXL inhibited NF-κB P65 expression and ventricular remodeling and suppressed the activation of NF-κB compared with the SHR group （P〈0.01, P〈0.05）. TXL reduced IκBα phosphorylation, increased expression of PPAR-γ protein and enhanced the physical interaction of the P65-P50 heterodimer with IκBα. The mRNA expression of PPAR-γ was enhanced but the mRNA expression of collagen Ⅰ mRNA and collagen Ⅲ mRNA were suppressed by TXL. Conclusions In spontaneously hypertensive rats, TXL could inhibit ventricular remodeling induced by hypertension, and the inhibitory effect might be associated with the process     

同型半胱氨酸对自发性高血压大鼠脑组织损伤免疫调节机制的研究

目的:探讨同型半胱氨酸（Hcy）对自发性高血压(SHR)大鼠脑组织损伤的免疫调节机制。方法:取60只SHR大鼠,随机分为SHR-C（对照组）、SHR-M（高蛋氨酸组）和SHR-T（治疗组）,每组20只。SHR-C普通饲料喂养,SHR-M给予2 mg/（kg·d）高蛋氨酸饮食。SHR-T组前8周给予2 mg/（kg·d）高蛋氨酸饮食,第9周开始给予叶酸4 mg/（kg·d）、维生素B12（VB12）0.09 mg/（kg·d）、维生素B6（VB6）0.09 mg/（kg·d）灌胃治疗。分别于第0、8、16周检测3组大鼠的体质量、收缩压（SBP）和血浆Hcy浓度。分别于第8、16周用ELISA测血浆中的IL-17和IL-10,实时定量PCR（Q-PCR）检测脑组织中IL-17和IL-10。第16周,免疫组织化学染色法检测脑组织中IL-17和IL-10表达情况。结果:第8周,SHR-M和SHR-T的体质量显著低于SHR-C,血浆Hcy浓度显著高于SHR-T,血浆IL-17浓度显著高于SHR-C,血浆IL-10浓度显著低于SHR-C,脑组织IL-10表达水平显著低于SHR-C（均P<0.05）;SHR-M和SHR-T各参数差异没有统计学意义（P>0.05）。第16周,经治疗后SHR-T组的体质量升高、血浆Hcy浓度下降,与SHR-M组比较具有显著性差异（P＜0.05）;SHR-T组的血浆IL-17浓度降低、IL-10浓度升高,与SHR-M组比较具有显著性差异（P＜0.05）;SHR-T组脑组织IL-17表达水平显著低于SHR-M组,IL-10表达水平显著高于SHR-M组（P>0.05）;SHR-M的脑组织IL-17细胞阳性率明显高于SHR-C和SHR-T,IL-10细胞阳性率明显高于SHR-C和SHR-T。结论:高同型半胱氨酸血症可促进炎症反应从而导致脑组织病变的发生,下调免疫反应后可起到保护作用。     

高血压大鼠肾脏基质金属蛋白酶及组织型基质金属蛋白酶抑制剂表达与活性的变化

[目的]研究在卒中易感型自发性高血压大鼠（stroke-prone spontaneously hypertensive rat,SHR-SP）肾脏中,基质金属蛋白酶（Matrix metalloproteinases,MMPs）-2,-9以及组织型基质金属蛋白酶抑制剂（tissue inhibitors of matrix metalloproteinases,TIMPs）-1,-2的表达与活性的变化.[方法]分别采用40只7周龄雄性SHR-SP大鼠及10只同周龄雄性Wistar-Kyoto大鼠作为高血压组与阴性对照组.观察期间定期测量各组大鼠无创鼠尾压.6个月后,处死存活大鼠留取血液及肾脏标本,测定血清肌酐及尿素氮浓度,采用组织病理染色观察两组大鼠肾脏组织学改变,采用明胶酶谱法分析存活大鼠肾脏MMP-2和MMP-9蛋白活性,并采用逆明胶酶谱法及蛋白质印迹分析TIMP-1和TIMP-2蛋白表达和活性.[结果]（1）明胶酶谱分析显示：SHR-SP肾脏中MMP-2活性较WKY组明显增高[（3.28±1.17） vs.（1.26±0.62）; P＜ 0.01].（2）逆明胶酶谱分析显示：高血压大鼠肾脏TIMP-2的活性明显高于WKY组[（1.12±0.43） vs.（0.78±0.34）,P＜0.05].（3）蛋白质印迹结果显示：高血压组大鼠肾脏TIMP-1、TIMP-2表达较对照组高[（TIMP-1：（3.44±0.13） vs.（2.31±0.15）,TIMP-2：（6.44±0.49）vs.（4.94±0.68）,P＜0.01].[结论]SHR-SP肾脏组织中MMP-2及TIMP-2的活性增高,TIMP-1及TIMP-2的表达均明显升高.     

The Expression of VIP and SP in the Cochlea of Spontaneously Hypertensive Rats and Its Implication

Hypertensioncaninducehearingloss ,whichmaybeduetodisruptionofbloodflow ,highbloodviscosityordysfunctionofneuropeptide ,butthemechanismsareunclear .Inrecentyears ,Lyonetal[1] reportedtheexpressionofvasoactiveintestinalpeptideimmunoreactivity (VIP IR)andsub…     

高血压对大鼠血管内皮细胞PPAR-gamma表达水平的影响

目的：探讨高血压对大鼠血管内皮细胞（ECs ）PPAR-gamma蛋白质和mRNA表达水平的影响。 方法：应用免疫组织化学法结合图像信号分析技术,以WKY大鼠为正常对照,检测4周,16周自发性高血压大鼠(SHR) ECs核内PPAR-gamma蛋白质表达水平,原代培养ECs并传代(≤3代),应用蛋白质免疫印迹和RT-PCR技术,检测ECs PPAR-gamma蛋白质和mRNA表达水平。 结果：4周 SHR血压较同龄WKY大鼠轻度升高（P＜0.05）,其ECs PPAR-gamma的蛋白质和mRNA水平略高于同龄WKY大鼠,但差异均无统计学意义（P＞0.05）。16周 SHR血压与16周 WKY大鼠相比明显增高（P＜0.01）,16周 SHR ECs PPAR-gamma的蛋白质和mRNA水平约为16周 WKY的1.5倍（P＜0.01）,且16周 SHR PPAR-gamma蛋白质和mRNA水平约为4周 SHR的2.5倍（P＜0.01）,而对照组16周 WKY大鼠PPAR-gamma水平较4周 WKY仅升高不到1倍（P＜0.01）。 结论：随SHR血压的升高和高血压病程的延长,ECs PPAR-gamma蛋白质和mRNA的表达水平均显著增高。     

Cx37和Cx40在自发性高血压大鼠不同动脉间的表达差异

目的：观察自发性高血压和正常血压大鼠肠系膜动脉和主动脉上连接蛋白（Cx）表达的变化。方法应用RT‐PCR和Wersternblot技术比较自发性高血压大鼠（SHR组）和正常血压大鼠（对照组）肠系膜动脉和主动脉上Cx37和Cx40的mRNA和蛋白表达水平。结果SHR组肠系膜动脉Cx37mRNA的表达降低（P＜0．05）,主动脉降低更为显著（P＜0．01）;肠系膜动脉Cx40mRNA的表达显著降低（P＜0．01）,而主动脉则没有变化（P＞0．05）。SHR组肠系膜动脉Cx37蛋白的表达降低（P＜0．05）,主动脉降低更为显著（P＜0．01）;肠系膜动脉Cx40蛋白的表达降低（P＜0．05）,而主动脉则没有变化（P＞0．05）。结论高血压可能通过降低血管细胞上Cx37和（或）Cx40的表达造成细胞间缝隙连接通讯异常。     

细胞外调节激酶的表达及活化在不同年龄自发性高血压大鼠心肌肥厚中的作用

目的:研究不同年龄的自发性高血压大鼠(spontaneously hypertensive rat,SHR)心室肌组织中细胞外调节激酶(extracellular signal-regulated kinases,ERKs)的表达及活化与心肌肥厚的关系.方法:选择Wistar Kyoto(WKY)大鼠作对照,SHR和WKY大鼠按年龄分为5周、8周、14周和24周各4组,以左心室质量与体重的比值反映心肌肥厚的程度;采用Western blot方法测定大鼠左心室心肌组织中基础表达ERK (basal ERK,b-ERK)和磷酸化ERK(phosphorylated-ERK,p-ERK)的水平.结果:①与相同周龄WKY大鼠比较,SHR自8周龄起血压明显升高(P<0.001),14周后心肌肥厚指数明显增加(P<0.01).②各年龄组SHR与相同周龄WKY大鼠b-ERK水平比较均无明显差异(P>0.05). ③5周龄SHR p-ERK水平与同龄WKY大鼠无差异,8到24周SHR大鼠p-ERK水平明显高于同龄WKY大鼠(P<0.01).④心肌肥厚指数与b-ERK量无明显相关性,与p-ERK量呈正相关. 结论:在SHR大鼠心肌肥厚形成中,心肌组织b-ERK没有增加,p-ERK水平增高,ERK活性增加参与高血压心肌肥厚过程.     

Differential protein expression in hypertrophic heart with and without hypertension in spontaneously hypertensive rats

Although cardiac hypertrophy in hypertension has been well recognized, the molecular mechanisms for the development of hypertrophy are still largely unknown. In this study, the protein expression profiles of left ventricular myocardia in spontaneously hypertensive rats （SHR） and Wistar-Kyoto （WKY） rats at different ages were analyzed using 2-DE in combination with MALDI-TOF/TOF MS/MS. The results showed that 20 proteins were modulated in the hypertrophic myocardium. Out of these modulated proteins, 13 proteins presented significant changes in SHR at an early stage prior to the development of sustained hypertension, while the changes of the other 7 protein expres- sions occurred only at a late stage in SHR when the blood pressure was significantly elevated, and were largely reversible by treatment with rennin-angiotensin-aldosterone system inhibitors losartan or enalapril. These data demonstrate that the changes in energy metabolism in the hypertrophied heart favor an increase in glycolysis and a decrease in oxidation of fatty acid and glucose, which occur at an early stage in SHR without hypertension. Our results also provide evidence to support the hypothesis that oxidative stress plays an important role in the development of hypertensive cardiac hypertrophy.     

Effect of acupuncture at Renying (ST 9) on gene expression profile of hypothalamus in spontaneously hypertensive rats

OBJECTIVE

To investigate changes in gene expression profiles in the hypothalamus related to the effects of acupuncture at the Renying (ST 9) acupoint in spontaneously hypertensive (SH) rats.

牛樟芝对易卒中的自发性高血压大鼠脑蛋白质组学的影响

目的 研究牛樟芝能否延长易卒中的自发性高血压大鼠的生存时间,并运用蛋白质组学方法对其作用机制进行探讨。 方法 先选取80只雄性易卒中的自发性高血压大鼠,随机分为给药组和对照组（每组40只）,给药组每天用牛樟芝（150 mg/kg）灌胃治疗,记录卒中大鼠的自然死亡时间。另外再选取6只易卒中的自发性高血压大鼠,随机分为给药组和对照组（每组3只）,给药组给予牛樟芝灌胃治疗（150 mg/kg）,连续90 d后取大鼠脑组织进行蛋白质组学研究,用WKY大鼠作为正常对照,对用药前后产生的差异蛋白点进行质谱鉴定,并用蛋白质印迹法进一步验证组学的鉴定结果。 结果 牛樟芝延长了易卒中的自发性高血压大鼠的生存时间（P<0.05）,蛋白质组学鉴定结果显示牛樟芝上调了脑组织抗氧化酶谷胱甘肽巯基转移酶（GST）和超氧化物歧化酶（SOD）的表达（P<0.05）,这一结果得到了蛋白质印迹法的验证。对脑组织氧化应激水平的研究发现机体的总抗氧化能力增强[T-AOC：（66.48±16.17） U/g vs （124.75±28.43） U/g, P<0.05）,表现在GST和SOD的酶活性增加[GST：（40.33±5.24） U/mg vs （70.50±6.24） U/mg, P<0.05; SOD：（109.25±23.61） U/mg vs （192.60±23.95） U/mg,P<0.05],而氧化应激产物丙二醛含量减少[（3.96±0.45） nmol/mg vs （2.04±0.31） nmol/mg,P<0.05]。 结论 长期服用牛樟芝能延长易卒中的自发性高血压大鼠的生存时间,这可能与其增加脑组织抗氧化酶的表达、减轻氧化应激的损伤有关。     

抗高血压因子对正常及高血压动物动脉平滑肌C...

Aorta segments (A) and mesenteric arteries (MA) from stroke prone spontaneously hypertensive rats (SHRsp) and control Wistar Kyoto rats (WKY) were used in the present study to assess the effect of AHF on Ca2+ influx in vascular smooth muscle (VSM). The results indicated that Ca2+ influx in VSM of SHRsp was much higher than that of WKY rats (P less than 0.05). AHF at 10(-7), 10(-6) and 10(-5) g/ml can significantly inhibit Ca2+ influx in a dose-dependent manner in VSM of both A and MA (P less than 0.05 and less than 0.01). The suppression effect of AHF on Ca2+ influx and the concentration-dependent relationship were more obvious in MA than in A. The Ca2+ influx in VSM of WKY rats was unaffected by administration of AHF.     

活血潜阳颗粒对自发性高血压大鼠血液流变学及纤溶系统活性的影响

目的探讨活血潜阳颗粒对自发性高血压大鼠(SHR)血液流变学、纤溶系统活性的影响。方法SHR 72只,随机分为活血潜阳颗粒大、中、小剂量组及卡托普利组、松龄血脉康组、双蒸水组,并以正常血压Wistar(WKY)大鼠为对照组,给药10周后检测各组大鼠血液流变学指标、血浆组织型纤溶酶原激活物(t-PA)及其抑制物(PAI)。结果与正常WKY大鼠比较,SHR全血黏度、血浆黏度、红细胞聚集指数均明显升高,而经活血潜阳颗粒治疗后上述各项指标较SHR组有不同程度改善(P<0.05或P<0.01)。SHR PAI升高、t-PA降低,经活血潜阳颗粒灌服后PAI降低、t-PA升高(P<0.05或P<0.01)。结论活血潜阳颗粒对自发性高血压大鼠血液流变学、纤溶系统活性具有调节作用。     

小电导型钙激活钾通道在自发性高血压大鼠阴茎海绵体中的表达

目的:探讨高血压对小电导型钙激活钾通道(SKCa)在大鼠阴茎海绵体中表达的影响及意义?方法:选用同龄雄性自发性高血压大鼠(SHR)及同系正常血压大鼠(WKY)各8只,10%利多卡因麻醉后连续检测海绵体内压(ICP)及平均动脉压(MAP),并用5 V电刺激海绵体神经(CN)记录ICP/MAP值变化?运用Western blot 和逆转录-聚合酶链式反应(RT-PCR)技术检测阴茎海绵体组织中SKCa蛋白和mRNA表达?结果:5 V电刺激后SHR组ICP/MAP值显著低于WKY组(0.31 ± 0.04 vs 0.76 ± 0.06),SKCa蛋白和mRNA的表达在SHR组(0.18 ± 0.01?0.39 ± 0.01)较WKY组(0.49 ± 0.02?0.81 ± 0.08)明显降低,差异具有统计学意义(P < 0.05)?结论:高血压可以降低大鼠勃起功能,这可能与自发性高血压大鼠阴茎海绵体组织中SKCa表达下降密切相关?