肝素结合表皮生长因子在高血压大鼠心肌表达及氯沙坦对其影响

目的探讨肝素结合表皮生长因子(HB-EGF)在自发高血压大鼠(SHR)心肌表达情况及氯沙坦对其影响.方法取16只8周龄自发性高血压大鼠,随机分为两组,每组8只:氯沙坦干预组,给予氯沙坦30 mg/kg*d溶于饮水灌胃治疗;SHR阳性对照组给予正常饮水.另有8只同龄同源雄性正常血压Wistar-kyoto大鼠(WKY)组作为正常对照组.实验周期12周.观察血压、左室重量/体重(LVW/BW);逆转录多聚酶链反应(RT-PCR)和免疫组化实验检测各组大鼠HB-EGF mRNA的表达情况.结果正常对照组和氯沙坦组血压和LVW/BW均底于SHR阳性对照组;SHR阳性对照组HB-EGF mRNA表达均高于正常对照组和氯沙坦组;氯沙坦组HB-EGF mRNA表达高于正常对照组.结论肝素结合表皮生长因子在自发高血压大鼠组表达明显增加而氯沙坦能部分阻断HB-EGF mRNA的表达提示HB-EGF mRNA可能在高血压发生发展过程中起了一定作用.     

缬沙坦对自发性高血压大鼠整合素β1和纤维黏连蛋白表达的影响

目的研究缬沙坦对自发性高血压大鼠(SHR)左室心肌整合素β1和纤维黏连蛋白(FN)表达的影响,探讨高血压心肌纤维化的机制.方法选用6周龄的雄性SHR 12只,随机均分为2组SHR阳性对照组;缬沙坦干预组(SHR-V),灌喂缬沙坦20 mg*kg-1*d-1.另选同源正常血压的WKY大鼠6只为正常对照组.实验期14周.观察血压、左室重量/体重(LVW/BW)、胶原容积分数,并用免疫组化法检测3组大鼠心肌整合素β1和FN的表达.结果缬沙坦可显著降低SHR的血压、LVW/BW及左室心肌的胶原含量,此外SHR阳性对照组整合素β1 和FN 的表达明显高于正常对照组(P<0.05),而SHR-V组两者的表达显著低于SHR阳性对照组(P<0.05).结论缬沙坦除可降低血压外,还能显著抑制整合素β1 和FN的表达,抑制甚至逆转心肌纤维化过程.     

自发性高血压大鼠心肌增殖细胞核抗原（PCNA）的表达以及厄贝沙坦和咪哒普利的影响

目的　探讨自发性高血压大鼠 (SHR)左心室肌增殖细胞核抗原 (PCNA)的表达以及咪哒普利、厄贝沙坦的影响。　方法　选用 13周龄的SHR30只 ,雌性 9只 ,雄性 2 1只 ,体重 2 2 8 5± 39g ,随机分为三组 ,使得每组雌性 3只 ,雄性 7只 ,分别设为SHR组 ,厄贝沙坦组 ,咪哒普利组 ;另选同源同系Wistar Kyoto大鼠 (WKY大鼠 ) 10只 ,雌性 5只 ,雄性 5只 ,体重 2 0 6 1g± 4 9 1g,作为正常对照组 (WKY组 )。实验期 14周。观察指标 :血压、左室重量 /体重 (LVW/BW )、左室厚度 /体重、心肌PCNA蛋白水平。结果　SHR组血压、LVW/BW、左室厚度 /体重均增高 ,心肌PCNA蛋白的表达明显增加 ;咪哒普利组、厄贝沙坦组血压、LVW/BW、左室厚度 /体重、心肌增殖核抗原 (PCNA)蛋白的表达均比SHR组低。结论　 2 6周龄SHR左心室肌PCNA蛋白的表达明显升高 ,咪哒普利、厄贝沙坦不仅可以良好地控制血压 ,而且可以抑制自发性高血压大鼠左心室重塑 ,并可以降低SHR左心室肌PCNA蛋白的表达 ,二者对SHR左室肥厚的抑制效应可能与降低PCNA蛋白的表达有关系。     

自发性高血压大鼠心肌增殖细胞核抗原(PCNA)的表达以及厄贝沙坦和咪哒普利的影响

目的探讨自发性高血压大鼠(SHR)左心室肌增殖细胞核抗原(PCNA)的表达以及咪哒普利、厄贝沙坦的影响. 方法选用13周龄的SHR30只,雌性9只,雄性21只,体重228.5±39 g,随机分为三组,使得每组雌性3只,雄性7只,分别设为SHR组,厄贝沙坦组,咪哒普利组;另选同源同系Wistar-Kyoto 大鼠(WKY大鼠)10只,雌性5只,雄性5只,体重206.1 g±49.1 g,作为正常对照组(WKY组).实验期14周.观察指标血压、左室重量/体重(LVW/BW)、左室厚度/体重、心肌PCNA蛋白水平.结果 SHR组血压、LVW/BW、左室厚度/体重均增高,心肌PCNA蛋白的表达明显增加; 咪哒普利组、厄贝沙坦组血压、LVW/BW、左室厚度/体重、心肌增殖核抗原(PCNA)蛋白的表达均比SHR组低.结论 26周龄SHR左心室肌PCNA蛋白的表达明显升高,咪哒普利、厄贝沙坦不仅可以良好地控制血压,而且可以抑制自发性高血压大鼠左心室重塑,并可以降低SHR左心室肌PCNA蛋白的表达,二者对SHR左室肥厚的抑制效应可能与降低PCNA蛋白的表达有关系.     

厄贝沙坦和咪哒普利对自发性高血压大鼠左室肥厚和c-Jun表达的影响

目的探讨厄贝沙坦和咪哒普利对自发性高血压大鼠（SHR）左室肥厚和c-Jun表达的影响。方法选用13周龄的SHR 30只,雌性9只,雄性21只,体质量（229±39）g,随机分为3组:SHR组,厄贝沙坦组,咪哒普利组,每组雌性3只,雄性7只。另选同源同系、血压正常的Wistar-Kyoto大鼠（WKY）10只,雌性5只,雄性5只,体质量（206±49）g,作为正常对照组（WKY组）。实验期14周。观察指标:血压、左室质量/体质量（LVW/BW）、左室厚度/体质量、左心室肌c-Jun蛋白及mRNA水平。结果26周龄SHR组血压、LVW/BW与左室厚度/体质量均增高,左心室肌c-Jun蛋白和mRNA的表达明显增加;咪哒普利组、厄贝沙坦组血压、LVW/BW、左室厚度/体质量、左心室肌c-Jun蛋白和mRNA的表达均降低。结论自发性高血压可明显导致心肌肥厚,而咪哒普利、厄贝沙坦可明显降低血压、抑制心肌肥厚的发生。     

氯沙坦对自发性高血压大鼠肾脏组织Bax、Bcl-2表达的影响情况

目的探讨氯沙坦对自发性高血压(SHR)大鼠肾脏组织Bcl-2相关性蛋白X(Bax)和B细胞淋巴瘤-2(Bcl-2)表达的影响。方法选取近交系雄性SHR大鼠30只和Wistar-Kyoto雄性大鼠15只,SHR大鼠随机分为氯沙坦组(n=15)和SHR阳性对照组(n=15),氯沙坦组按氯沙坦30 mg/kg灌胃,SHR阳性对照组按0.9%氯化钠溶液10 ml/kg灌胃,Wistar-Kyoto大鼠作为正常对照组,按0.9%氯化钠溶液10ml/kg灌胃,每日清晨灌胃,连续灌胃8周。比较各组大鼠尾动脉收缩压,采用免疫组化染色法检测两组Bax和Bcl-2蛋白表达,采用荧光定量聚合酶链反应(PCR)检测Bax和Bcl-2 m RNA表达水平。结果氯沙坦组给药第4周和8周尾动脉收缩压明显低于给药前收缩压水平(P0.05);氯沙坦组给药第4周和8周尾动脉收缩压低于SHR阳性对照组(P0.05);氯沙坦组和正常对照组Bcl-2平均光密度分别为(0.19±0.01)和(0.20±0.02),明显高于SHR阳性对照组(P0.05),而Bax平均光密度分别为(0.12±0.02)和(0.13±0.01),明显低于SHR阳性对照组(P0.05);氯沙坦组和正常对照组Bax和Bcl-2平均光密度比较差异无统计学意义(P0.05);Bcl-2和Bax m RNA相对表达量在氯沙坦组和正常对照组间差异比较无统计学意义(P0.05),SHR阳性对照组患者的Bcl-2相对表达值显著高于氯沙坦组和正常对照组,而Bax m RNA相对表达值显著低于氯沙坦组和正常对照组(P0.05)。结论氯沙坦对SHR大鼠有明显的降压作用,可抑制Bax基因及蛋白表达,而促进Bcl-2基因及蛋白表达。     

替米沙坦对自发性高血压大鼠左心室重构的影响

目的 研究替米沙坦对自发性高血压大鼠(SHR)左心室重构的影响.方法 16只12周龄雄性SHR,随机分为替米沙坦组和SHR空白对照组,每组8只;另设同龄Wistar大鼠(WKY)8只为正常对照组.治疗组给予替米沙坦10 mg·kg-1·d-1灌胃给药,饲养8 w后处死动物,测量左心室重量及心肌厚度,计算左心室重量与体重比(LVW/BW);通过Van Gieson染色法观察左心室心肌胶原纤维变化,对左心室心肌胶原容积分数(CVF)和血管周围胶原面积(PVCA)进行分析;电镜和HE染色观察左室心肌超微结构.结果 与正常对照组WKY大鼠相比,SHR空白对照组的尾动脉收缩压(SBP)、LVW/BW、左室壁厚度、CVF、PVCA均显著增高(P＜0.01);与SHR空白对照组相比,替米沙坦组能有效降低SHR的SBP,改善左心室肥厚(P＜0.01),减少心肌间质及心肌小动脉周围的胶原(P＜0.01),组织病理及电镜显示,替米沙坦治疗能显著改善SHR左心室重构.结论 替米沙坦能有效降低SHR血压,改善左心室重构.     

依贝沙坦对自发性高血压大鼠左心室肥厚和心肌纤维化的影响

目的探讨依贝沙坦对自发性高血压大鼠(SHR)左心室肥厚(LVH)和心肌纤维化的影响。方法18只16周龄SHR,随机分为依贝沙坦治疗组(SHR-I)和SHR空白对照组(SHR-C);另设同源的WKY大鼠8只为正常对照组。治疗组口服依贝沙坦50mg.kg-1.d-1给药8周后处死动物,取左心室心肌称重,计算左心室/体重比(LVW/BW),Masson三色法染色观察左心室心肌胶原变化,计算机图象分析测量心肌切片的胶原容积分数(CVF)和血管周围胶原面积(PVCA)。结果SHR空白对照组的收缩压(SBP),LVW/BW,CVF,PVCA均显著高于WKY对照组(P<0.01),与SHR空白对照组相比,依贝沙坦治疗组能有效降低SHR的SBP,改善左心室肥厚(P<0.01)并使左心室内膜及心肌小动脉周围的胶原减少(P<0.01)。结论依贝沙坦可有效降低SHR血压,部分逆转心肌纤维化和左心室肥厚。     

福辛普利对SHR左室肥厚和心肌纤维化的影响

目的探讨福辛普利对自发性高血压大鼠(SHR)左心室肥厚(LVH)和心肌纤维化的影响。方法18只16周龄SHR大鼠,随机分为福辛普利治疗组(SHR-F)和SHR空白对照组(SHR-C);另设同源的WKY大鼠8只为正常对照组。治疗组口服福辛普利20mg·kg-1·d-1,给药8周后处死动物,取左心室心肌称重,计算左心室/体重比(LVW/BW),Masson三色法染色观察左心室心肌胶原变化,计算机图像分析测量心肌切片的胶原容积分数(CVF)和血管周围胶原面积(PVCA)。结果SHR空白对照组的SBP、LVW/BW、CVF、PVCA均显著高于WKY对照组(P<0.01),与SHR空白对照组相比,福新普利治疗组能有效降低SHR的SBP,改善SHR左心室肥厚(P<0.01〉并使左心室内膜及心肌小动脉周围的胶原减少(P<0.01〉。结论福辛普利可有效降低SHR血压,部分逆转心肌纤维化和左室肥厚。     

阿托伐他汀对自发性高血压大鼠心肌组织p21表达的影响及其意义

目的:观察阿托伐他汀(ATV)对自发性高血压大鼠(SHR)心肌组织中p21表达的影响,探讨其改善心肌肥厚的可能机制。方法:将16只8周龄SHR随机分为2组(n=8):ATV药物干预组(ATV组)与SHR模型对照组(SHR组),并以8只同周龄Wistar-Kyoto大鼠作为正常对照组(WKY组)。ATV组用ATV 50 mg/(kg·d)灌胃,SHR组与WKY组采用等容量蒸馏水每日同时灌胃。每隔2周测1次血压。10周后,观察大鼠血脂、心肌肥厚指标、p21 mRNA及其蛋白表达的改变。结果:干预10周后,ATV组及SHR组血脂、血压无明显差异。ATV组左室质量指数低于SHR组(P<0.01)。ATV组p21mRNA及蛋白的表达明显高于SHR组(P<0.01)。心肌组织p21mRNA的表达与全心质量与体质量比(HW/BW)呈负相关(r=-0.709,P<0.01),与左室质量与体质量比(LVW/BW)呈负相关(r=-0.665,P<0.01)。结论:ATV可上调SHR肥厚心肌组织中p21的表达,可有效改善左室肥厚。     

Growth hormone in the regulation of hyperlipidemia

Plasma concentrations of triglyceride, cholesterol, and apolipoproteins A-I and B in young growth hormone deficient subjects were measured at intervals during the five weeks after initial hormone-replacement therapy. The mean concentrations of cholesterol, apolipoproteins A-I and B decreased significantly during that period: the decreases were progressive and in similar proportion to each other. Also, the amount by which apolipoprotein A-I concentration decreased was correlated with its plasmas concentration before treatment. The data suggests that growth hormone may play a role in the regulation of these three major plasma lipoprotein components and tend to suppress the development of hypercholesterolemia which has been observed in some adult growth hormone deficient subjects.     

Blood Vessel Growth in the Endometrium

Angiogenesis, or formation of new blood vessels by sprout formation from existing vessels, is generally considered to be the only mechanism by which blood vessel growth occurs. This traditional concept of angiogenesis has been derived largely from observations of experimental systems. Relatively fewer studies on angiogenesis have been carried out using normal angiogenic situations where vessel growth occurs in a controlled three-dimensional fashion throughout the tissue. Recent advances in the treatment of infertility and outpatient gynecological procedures have led to greater accessibility to normal human endometrium, thus providing new opportunities to study the process of angiogenesis in a physiological context. However, to date, it appears that very little work had been done in relation to endometrial angiogenesis apart from the location of numerous angiogenic and other growth factors with potential to influence angiogenesis in the endometrium, and here there have been few attempts to link these observations with actual angiogenic events. The purpose of this review is to summarize the literature regarding angiogenesis in the endometrium, including work from our own laboratory, and to suggest that blood vessel growth in the endometrium may occur by a mechanism that differs from classical angiogenesis.     

Growth hormone deficiency in the adult

Growth hormone deficiency (GHD) in adults may be of either adult or childhood onset and may occur as isolated GHD or as multiple hormone deficiencies. Adult-onset GHD (AoGHD) usually results from damage to the pituitary gland or hypothalamus. GH is frequently undetectable in normal subjects and thus GHD cannot be distinguished from the normal state using a single random GH measurement. In general, a stimulation test is required to recognize GHD. Insulin tolerance test (ITT) has been considered the gold standard by the most important scientific societies, although alternative tests, in particular GHRH plus arginine have been proposed as valuable alternative to ITT. The clinical syndrome associated with AoGHD is characterized by a wide array of symptoms and important chronic complications, such as cardiovascular complications, which may be responsible for an increased mortality. The rationale for GH replacement in adults GHD patients is justified by the beneficial effects on some clinical end-points, such as quality of life (QoL) and cardiovascular risk factors, whereas the effects on mortality risk are still controversial. Over the recent years, guidelines on the use of rhGH as a substitution treatment in adult hypopituitarism have been issued by international (Growth hormone research society-GRS, Endocrine Society) and relevant national (National Institute of Clinical Excellence-UK, NICE) institutions. The aim of the paper is to review and discuss these guidelines.