灯盏花对自发性高血压大鼠心室重构的药物干预研究

目的　观察蛋白激酶C抑制剂—灯盏花对SHR心脏血管重构逆转作用。方法　将 10月龄 12只SHR(SHR10 )随机分为 :灯盏花 (SHRD)、和生理盐水组 (SHRc) ,均以 10mg·kg 1·d 1腹腔内射给药 8周。测定血压、心室重量指数 ,偏振光镜、透射电镜观察心脏、血管结构改变。图象分析计算心肌间质胶原面积、含量。结果　灯盏花组左心室肥厚不同程度消退 ,明显改善心肌细胞肥大、变性 ,胶原容积分数 (CVF)降低 (P <0 0 5 )。结论　灯盏花可逆转心室重构 ,改善心肌僵硬度 ,具有心脏保护作用。     

灯盏花对自发性高血压大鼠心室重构的药物干预研究

目的　观察蛋白激酶C抑制剂椀普祷ǘ許HR心脏血管重构逆转作用.方法　将10月龄12只SHR(SHR10)随机分为:灯盏花（SHRD）、和生理盐水组(SHRc),均以10?mg*kg-1*d-1腹腔内射给药8周.测定血压、心室重量指数,偏振光镜、透射电镜观察心脏、血管结构改变.图象分析计算心肌间质胶原面积、含量.结果　灯盏花组左心室肥厚不同程度消退,明显改善心肌细胞肥大、变性,胶原容积分数（CVF）降低（P<0.05）.结论　灯盏花可逆转心室重构,改善心肌僵硬度,具有心脏保护作用.     

Catestatin could ameliorate proliferating changes of target organs in spontaneously hypertensive rats

Background Catestatin,a chromogranin A-derived peptide,is a potent antagonist of nicotine-evoked catecholamine release.We know that catecholamine plays an important role in cardiovascular remodeling in...     

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     

Antihypertension and anti-cardiovascular remodeling by phenylalanine in spont aneously hypertensive rats: effectiveness and mechanisms

Objective To investigate mechanisms of anti-hypertensi on and anti-cardiovascular remodeling by phenylalanine (phe) in spontaneously h ypertensive rats (SHRs).Methods The comparison of blood pressure (BP) increment with the ages and cardiovascular changes of SHRs was made between the 3% phe-intervented group (SHR-phe) and t he control SHRs group. Detection of the structural changes with the VID AS digital vedio-fre quency processing technique and light and electron microscopy were made. The ce ll growth and proliferation of cultured smooth muscle cells (CSMCs) of the thora cic aortas or myocardial fibroblasts were evaluated by measuring the (3)H -th ymidine counts per minute (cpm) incorporated into the new synthesized desoxyribo nucleic acid (DNA) and determining the cell number with the crystal violet stain technique. The Ca((2+)) influx was measured in counts/min of (45)CaCl(2) after incubating it with 5 different concentrations of phen ylalanine and the intracellular ［Ca((2+))］(i) by Fura-Ⅱ/Am indicator. The total messenger ribonucleic acid (mRNA) of the myocardium was extracted and Northern blot analysis was performed with the probe collagen α(2)(Ⅰ)cDNA . The tyrosine hydroxylase (TH) activity was measured by high -performance liquid chromatography (HPLC) with electrochemical detector after h aving reacted with its substrate tyrosine and other reagents. The catecholamine contents in brain homogenat were detected by HPLC method. The comparison of p harmacokinetics of phenylalanine among SHR-phe, SHRs and control Wistar Kyoto (WKY) rats was made after intravenous injection of (3)H-L-phe (1 ml/k g) by PK-GRAPH Program for kinetic calculation. The (3)H-L-pheuptake by CSMCs after incubating for difinite intervals was also detected and compa red. Results Phenylalanine could prevent the increase of BP with ages and the heart weight (h eart/body weight index). The aortic media thickness and the collagen content in the myocardium were decreased significantly in SHR-phe. Whereas the dearrange d cardiovascular structure was much improved. The mechanisms might be direct and specific inhibition of the DNA synthesis and proliferation of cardiovascular cells which may be related to the inhib ition of collagen α(2)(Ⅰ)cDNA, c-fos and c-myc expression. Other mechan isms may include decrease of intracellular ［Ca((2+))］(i) and an inhibition of central sympathetic activity due to the results of higher TH activity in the caudate nucleus and higher adrenaline conte nt in the posterior hypothalamus. Besides, partial recovery of p henylalanine metabolic aberrants existed in SHRs seems to be another possibility for its effectiveness. Conclusions Phenylalanine intervention could exert a definite anti-hypertension and anti-c ardiovascular remodeling effects on SHRs like seen in human essential hypertensi on. Its mechanisms might be related to direct inhibition of growth in the cardi ovascular cells, decrease of central sympathetic activity, the reverse of the exhibited phenylalanine metabolic aberrants in SHRs, and a decrement of intracellu lar ［Ca((2+))］］(i).     

氯沙坦减轻自发性高血压大鼠主动脉重构及其机制

目的：观察氯沙坦治疗对自发性高血压大鼠(SHR)主动脉重构及p22phox表达的影响。方法：36只12周龄SHR连续灌胃给予氯沙坦,剂量分别为0,15,30 mg/(kg·d),每组12只;另取12只WKY大鼠作为非高血压对照组。每周测定尾动脉压。8周后检测主动脉病理结构、血浆过氧化氢（H2O2）水平、过氧化氢酶 (CAT)活力、血浆血管紧张素Ⅱ(Ang II)水平、主动脉p22phox的表达。结果：SHR主动脉血管壁明显增厚,尾动脉压、血浆H2O2和AngⅡ水平及主动脉p22phox的表达均显著增高,而血浆CAT活力明显下降;应用氯沙坦治疗在降低血压的同时,可改善SHRL主动脉结构,降低血浆H2O2水平和主动脉p22phox的表达,升高血浆AngⅡ水平及和CAT活力。结论： SHR主动脉血管重构涉及氧化应激,氯沙坦可改善血管重构,其机制与下调p22phox表达、抑制氧化应激有关。     

Electrical remodeling of membrane ionic channels of hypertrophied ventricular myocytes from spontaneously hypertensive rats

Ｍｅｔｈｏｄｓ　Ｍｅｍｂｒａｎｅｉｏｎｉｃｃｈａｎｎｅｌｓｗｅｒｅｓｔｕｄｉｅｄｉｎｅｎｚｙｍａｔｉｃａｌｌｙｄｉｓｐｅｒｓｅｄｓｐｏｎｔａｎｅｏｕｓｌｙｈｙｐｅｒｔｅｎｓｉｖｅｒａｔｓ (ＳＨＲｓ)ｌｅｆｔｖｅｎｔｒｉｃｕｌａｒｍｙｏｃｙｔｅｓｕｓｉｎｇｔｈｅｗｈｏｌｅ ｃｅｌｌｃｏｎｆｉｇｕｒａｔｉｏｎｏｆｐａｔｃｈ ｃｌａｍｐｔｅｃｈｎｉｑｕｅ ,ｗｉｔｈｎｏｒｍａｌＷｉｓｔａｒｒａｔｓｖｅｎｔｒｉｃｕｌａｒｍｙｏｃｙｔｅｓａｓｃｏｎｔｒｏｌｓ Ｗｅｏｂｓｅｒｖｅｄｄｅｐｏｌａｒｉｚｉｎｇｃｕｒｒ…     

自发性高血压大鼠颈动脉中膜细胞外基质的变化——替米沙坦的干预研究

目的:研究自发性高血压大鼠(SHR)颈动脉中膜细胞外基质(ECM)的变化及替米沙坦对其的影响。方法:将12周龄的SHR随机分为高血压组、替米沙坦高剂量组(Tel-H)、替米沙坦低剂量组(Tel-L),另设同性别、同周龄的WKY大鼠为对照组(n=10),实验开始及每两周测鼠尾收缩压(SBP),18周后终止实验,麻醉后取颈总动脉,颈动脉切片。颈动脉中膜纤维黏连蛋白(FN)、层黏连蛋白(LN)的表达以SP免疫组化染色评估。结果:两周后Tel-H组的SBP显著低于SHR组(P0.05);SHR组颈动脉中膜的FN、LN积分光密度(IOD)明显高于WKY组(P<0.01);Tel-H、Tel-L组颈动脉中膜FN、LN的IOD分别明显低于SHR组(P<0.01)。结论:30周龄SHR颈动脉中膜ECM发生了明显重构,表现为胶原、FN、LN沉积增多,而弹力纤维减少;替米沙坦治疗能减少上述ECM的改变,从而减轻颈动脉的重构。     

吲哒帕胺联合依那普利对自发性高血压大鼠的降压效果

目的研究吲哒帕胺联合依那普利对自发性高血压大鼠(SHR)的降压效果。方法40只SHR随机分成四组(n=10):空白对照组、吲哒帕胺组、依那普利组、吲哒帕胺 依那普利组。以灌胃方式分别给予不同剂量药物。观察不同剂量及药物处理状况下,SHR体质量、心率和血压的变化。结果给药期间及给药后,各药物组不同剂量给药对SHR体质量的增长和心率均无明显影响。吲哒帕胺 依那普利组SHR经不同剂量给药后,血压均较给药前显著降低(P均<0.05),其降压程度与单一药物组相比效果更明显(P<0.05)。结论吲哒帕胺联合依那普利比单一降压药更能显著降低SHR的血压。     

心脏肥大细胞密度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及对照Wistar Kyoto大鼠(WKY)的收缩压(SBP)、左心室重量指数(LVI)、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(PVCA)和心肌Ⅰ、Ⅲ型胶原mRNA表达的变化.肥大细胞密度与LVI、CVF及PVCA之间的关系采用相关分析.结果与WKY组比较,SHR组SBP、LVI、心肌细胞直径、心肌细胞短径、肥大细胞密度、CVF、PVCA、心肌Ⅰ、Ⅲ型胶原含量均明显增加(P＜0.01).心脏肥大细胞密度与LVI、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.     

安体舒通对自发性高血压大鼠肺组织胶原形成的抑制作用

观察自发性高血压大鼠肺胶原的变化及安体舒通的作用，探讨醛固酮在肺胶原代谢中的意义。方法：用放射免疫法测定血浆与肺组织的醛固酮含量，肺组织的胶原采用改良的Ｂｅｒｇｍａｎ法测羟脯氨酸含量。结果：ＳＨＲ肺组织胶原含量明显增加，安体舒通可显著抑制ＳＨＲ胶原的增加程度。     

自发性高血压大鼠丙泊酚麻醉后的认知功能研究

目的评估自发性高血压大鼠(SHR)丙泊酚麻醉后的认知功能。方法将24只3月龄雄性SHR随机分为对照组和丙泊酚组,分别腹腔注射等体积的生理盐水和丙泊酚。采用无创尾动脉血压测定分析系统测量给药前、给药后即刻和给药后3 h大鼠的平均动脉压(MAP)和脉搏变化情况。采用经典Morris水迷宫,给药后1 d开始行定位航行实验,连续7 d,比较两组的逃避潜伏期;第7天去除平台行空间探索实验,比较两组停留在原平台象限的时间百分比。结果丙泊酚组给药后即刻和给药后3 h的MAP和脉搏较基础值和对照组均显著下降,差异有统计学意义(P<0.05)。随着学习时间的延长,两组逃避潜伏期均逐渐缩短,其中训练第2～4天,对照组的逃避潜伏期明显短于丙泊酚组,差异有统计学意义(P<0.05);第5～7天,两组成绩逐渐接近,差异无统计学意义(P>0.05)。空间探索实验显示,两组大鼠在原平台象限的停留时间百分比超过25%,均高于其他象限。结论经丙泊酚麻醉的SHR会出现一过性的血压和脉搏下降,并在短期内产生认知功能障碍,主要表现在训练初期;给予足够训练后的SHR认知功能可恢复到正常水平。     

自发性高血压大鼠心肌间质重构的实验研究

目的：观察高血压心肌间质重构。方法：采用不同月龄自发性高血压大鼠（ＳＨＲ）为实验动物模型,从胶原定性和定量指标观察心肌间质重构。结果：ＳＨＲ１０与ＷＫＹ１０比较胶原面积（交原容积分数（ＣＶＦ）增高１．４倍;ＳＨＲ１８－２２量高,与ＳＨＲ１０比较ＣＡ、ＣＶＦ增高２．４倍（ＫＰ〈０．０１）。ＣＶＦ比左室重量指数（ＬＶＷ／ＢＷ）增加更明显,结论：ＳＨＲ心肌间质、冠脉血管均发生了重构,ＳＨＲ１８－２２心肌     

肾上腺髓质素对自发性高血压大鼠肾脏微小动脉的影响

目的探讨肾上腺髓质素（Adrenomedullin, ADM）对自发性高血压大鼠（SHR）肾脏微小动脉的影响及与磷酸化细胞外调
节蛋白激酶1/2（ERK1/2）的关系。方法4周龄雄性SHR随机分为ADM治疗组（ADM组）和高血压对照组（SHR组）,以WKY
大鼠作为空白对照,ADM组皮下注射ADM（1.0 nmol/kg·d,每周5 d）。采用组织学、组织化学、免疫组织化学和Western blot技
术,对比观察平均动脉收缩压、肾微小动脉组织学变化和磷酸化ERK1/2表达。结果从8周龄开始,SHR和ADM组血压开始升
高,16和24周龄平均动脉收缩压明显高于WKY组,ADM治疗组24周龄时平均动脉收缩压明显低于非治疗SHR组;在16和24
周龄,SHR组和ADM组大鼠肾脏微小动脉中膜/内径比值明显大于WKY组（P<0.05）;ADM组大鼠肾脏微小动脉中膜/内径比
值的增幅略低于SHR组,其中外径小于40 μm动脉中膜/内径比值在24 周龄时明显小于SHR组（P<0.05）。免疫组织化学和
Western blot显示16和24周龄SHR和ADM组大鼠肾脏组织磷酸化ERK1/2表达显著高于WKY组（P<0.05）,24周龄时ADM组
肾脏磷酸化ERK1/2表达显著低于SHR组（P<0.05）。结论较长时间使用ADM,在一定程度上能够减轻自发性高血压大鼠血
压升高程度,可能通过抑制ERK1/2的磷酸化减轻肾微小动脉的重构。
     

依那普利、福辛普利逆转高血压心室重塑的实验研究

目的 观察血管紧张素转换酶抑制剂Ｅｎａｌａｐｒｉｌ和Ｆｏｓｉｎｏｐｒｉｌ对ＳＨＲ心脏血管重塑逆转作用。方法 将１０月龄１８只ＳＨＲ（ＳＨＲ１０）随机分为Ｅｎａｌａｐｒｉｌ（ＳＨＲＥ）、Ｆｏｓｉｎｏｐｒｉｌ（ＳＨＲＦ）和生理盐水（ＳＨＲｃ）三组，给药剂量为１０ｍｇ／ｋｇ／ｄ腹腔内注射连续８周。测定血压、心室重量指数，用偏振光镜观察心脏、血管结构改变。图象分析计算心肌间质胶原面积、含量。结果 两药物均     

厄贝沙坦和咪哒普利抑制自发性高血压大鼠左心室与阻力血管重塑的实验研究

目的 探讨咪哒普利、厄贝沙坦对自发性高血压大鼠（SHR）左心室与阻力血管重塑的抑制作用并比较二者的作用效果。方法 选用13周龄的SHR30只、WKY大鼠10只分为4组：SHR组，厄贝沙坦组，咪哒普利组，WKY组。实验期15周。观察心血管重塑珠有关指标。结果 咪哒普利组、厄贝沙坦组血压控制良好，左心室有和肠系膜动脉重塑的各项指标改善，在这些指标上二者无显著性差异；心肌和肠系膜动脉结构改变尤其是纤维化均减轻，咪哒普利组减轻更明显。结论 咪哒普利、厄贝沙坦不仅能良好地控制血压而且可以抑制自发性高血压大鼠左心室与阻力血管重塑；在防止心肌和肠系膜动脉结构改变尤其是纤维化方面，咪哒普利作用优越于厄贝沙坦。     

Atorvastatin prevents connexin43 remodeling in hypertrophied left ventricular myocardium of spontaneously hypertensive rats

Background  Connexin43 (Cx43) is the predominant gap junction protein in heart and is involved in the control of cell-to-cell communication to modulate the contractility and the electrical coupling of cardiac myocytes. Left ventricular (LV) hypertrophy is accompanied by changes of Cx43 expression. Recent studies have demonstrated that statins reduced cardiac hypertrophy. However, it is unknown whether statins can affect Cx43 expression in hypertrophied left ventricular myocardium. This study was designed to assess the effects of atorvastatin on LV hypertrophy and Cx43 expression in spontaneously hypertensive rats (SHR).
Methods  Nine-week old SHRs were randomly divided into two groups. Some received atorvastatin at 30 mg/kg by oral gavage once daily for 8 weeks (SHR-A); others received vehicle. Age-matched Wistar-Kyoto rats (WKY) received atorvastatin or vehicle for 8 weeks were used as controls. At the end of the experiment, we investigated LV hypertrophy and the expression of Cx43 in LV myocardium in four groups. Cx43 expression was investigated by the methods of Western blotting, immunohistochemistry, and transmission electron microscope. LV hypertrophy was accessed by pathological analysis and plasma brain natriuretic peptide (BNP) level.
Results  LV hypertrophy was prominent in untreated SHR. In SHR, LV myocardium Cx43 level was upregulated, and the distribution of Cx43 was displaced from their usual locations to other sites at various distances away from the intercalated disks. After atorvastatin treatment, myocardium Cx43 level was reduced in SHR-A, and the distribution of Cx43 gap junction became much regular and confined to intercalated disk. Statins also prevented LV hypertrophy in SHR.
Conclusions  These results provide novel in vivo evidence for the key role of Cx43 gap junctions in LV hypertrophy and the possible mechanism in anti-hypertrophic effect of statins. Atorvastatin treatment may have beneficial effects on LV hypertrophy in spontaneously hypertensive rats.

     

粒细胞集落刺激因子对自发性高血压大鼠心室重构的调控

目的研究早期反复给予大剂量粒细胞集落刺激因子（granulocyte colony stimulating factor,G-CSF）动员骨髓干细胞,对自发性高血压大鼠早期心室重构的调控作用。方法 30只10周龄自发性高血压大鼠,随机分为3组,每组10只。G-CSF组连续接受4个周期用药动员骨髓干细胞,1个周期持续14 d,前5 d皮下注射G-CSF50μg/（kg·d）,后9 d不用药物;假性实验组干预药物为生理盐水,注射方法同G-CSF组;空白对照组不用药物。饲养8周后,进行动物超声心动图检查室间隔厚度（interventricular septal thickness,IVST）和左室短轴收缩率。麻醉条件下解剖取大鼠心室,计算心室质量/体质量,左心室心肌病理切片观察。结果 G-CSF组较假性实验组及空白组心室/体质量增加（P〈0.01）,IVST增加（P〈0.05）,左室短轴收缩率明显改善（P〈0.05）。病理结果显示,GCSF组较假性实验组及空白组心肌纤维排列整齐,心肌胶原容积分数和血管周围胶原面积明显降低（P〈0.05）。结论早期反复大剂量G-CSF动员骨髓干细胞,促进心脏适应性肥厚,提高心肌收缩力,抑制心肌纤维化,减轻不良重构,维持心脏功能。     

自发性高血压大鼠丙泊酚麻醉后海马组织的蛋白质组学研究

目的观察丙泊酚麻醉对自发性高血压大鼠海马组织蛋白质表达的影响及其与认知功能的关系。方法40只自发性高血压大鼠随机分为实验组（n=20）和对照组（n=20）。实验组经腹腔注射丙泊酚100mg／kg,1h和2h后追加首剂量的1／2,维持麻醉3h;对照组采用同样方法和剂量给予生理盐水作为对照。分别于给药后3、24、72h及7d时,随机选取两组大鼠各5只,取海马组织提取总蛋白样品。采用双向凝胶电泳分离蛋白样品,分析差异表达蛋白点（差异〉2倍的蛋白质点）,基质辅助激光解析电离飞行时间质谱（MALDI．TOF．MS）鉴定。通过数据库检索分析差异蛋白的主要功能和参与的生物学过程。结果获得差异表达的蛋白质点共有84个,其中68个经MALDI—TOF—MS成功鉴定,去冗余后经蛋白质数据库搜寻确定了47个差异表达蛋白。以蛋白的低表达为主,持续到麻醉后第7日。多种生物学过程（涉及能量代谢、线粒体功能、蛋白折叠和囊泡转运等）受到影响。结论自发性高血压大鼠丙泊酚麻醉后海马组织蛋白发生多维、动态改变,部分蛋白的差异表达可能参与认知功能损害的分子机制,具体作用有待进一步深入探讨。     

自发性高血压大鼠脂联素及其受体 1 的表达与心血管重构的关系

目的观察自发性高血压大鼠（SHR）血清脂联素（APN）,心肌、主动脉脂联素受体1（AdipoRl）的表达,探讨三者与血压升高、心血管重构的关系。方法选取22周龄SHR和Wistar—Kyoto（WKY）大鼠各8只为研究对象,测定血清APN、血清空腹胰岛素（FINS）,实时荧光定量PCR法测定心肌、主动脉AdipoRlmRNA表达。结果与同周龄WKY组比较,SHR组收缩压升高,IR程度增加,心脏重量指数（HWI）和左心室重量指数（LVwI）增加,主动脉中膜（MT）增厚、壁腔比值（MT／LD）增加,血清APN水平、心肌、主动脉AdipoRlmRNA表达下降（P〈0．05）,血清APN（X1）、主动脉AdipoRlmRNA（X2）、HOME—IR（X3）、SBP（x4）与MT／LD有关。结论SHR存在显著的心血管重构,APN及AdipoR1表达下降、IR程度增加;APN及AdipoRl可能是预防高血压及高血压心血管重构的重保护因素。