心房和心室M受体密度的种属差异性比较

目的:比较大鼠、豚鼠和家兔心房肌和心室肌M受体分布密度及与其强阻断剂氚标记二苯羟乙酸奎宁酯（3HQNB）亲和活性的种属差异性。方法:运用放射性配基受体结合法测定不同动物心房肌和心室肌M受体密度及解离常数（Kd）值。结果:①大鼠心房M受体的分布密度约为心室的3.0倍,家兔心房是心室的4.0倍,而豚鼠心房是心室的1.7倍。②M受体在不同种动物心房肌密度排序:家兔>大鼠>豚鼠。心室肌密度排序:豚鼠>大鼠>家兔。Kd值在心房、心室及种间均无统计学差异。结论:①M受体在大鼠、豚鼠和家兔心脏的分布密度不仅具有房室间差异性,而且还有种间差异性。②M受体与其阻断剂3HQNB亲和活性的种间差异性不明显。     

顿抑心肌组织降钙素基因相关肽的免疫组织化学研究

采用大鼠心肌顿抑模型,用免疫组织化学方法观察了顿抑心肌组织中降钙素基因相关肽（ＣＧＲＰ）的改变,结果发现心脏中存在ＣＧＲＰ阳性免疫神经纤维,尤其是心房,冠脉周围,乳头肌以及心室肌中,顿抑心肌中ＣＧＲＰ纤维密度显著减少。     

植物神经与心律失常

心律失常是临床常见的心脏异常表现之一,而绝大多数心律失常的发生均与植物种经功能紊乱有关。它既可发生于正常人,亦可在器质性心脏病的基础上发生或是全身性疾病在心脏的异常表现。一、植物神经在心脏的分布心脏受心交感和迷走神经双重神经支配。交感神经节后纤维分布遍及整个心房和心室;迷走神经节后纤维则以窦房结、心房和房室结为主。以往认为心室肌不受迷走神经支配,但是近年的研究表明,心室肌有迷走神经分布并对心室肌的电生理活动产生影     

正常及顿抑心肌组织CGRPmRNA原位杂交研究

在大鼠心肌顿抑模型上采用原位杂交技术观察了正常及顿抑心肌组织降钙素基因相关肽ｍＲＮＡ表达的情况。结果发现正常心房及心室肌组织中存在ＣＧＲＰｍＲＮＡ,心脏的血管周围也有分布。顿抑心肌组织中ＣＧＲＰｍＲＮＡ阳性表达显著减弱。     

顿抑心肌组织降钙素基因相关肽的免疫组织化学研究

采用大鼠心肌顿抑模型，用免疫组织化学方法观察了顿抑心肌组织中降钙素基因相关肽（ＣＧＲＰ）的改变。结果发现心脏中存在ＣＧＲＰ阳性免疫神经纤维，尤其是心房、冠脉周围、乳头肌以及心室肌中。顿抑心肌中ＣＧＲＰ纤维密度显著减少。     

实验性糖尿病大鼠心肌ATⅡ和心肌超微结构的研究

观察了链脲佐菌素实验性糖尿病大鼠心房、心室肌血管紧张素Ⅱ（ＡＴⅡ）和心房、心室肌超微结构的改变，结果表明，病程１４天的糖尿病大鼠心房、心室肌ＡＴⅡ显著高于正常对照组（Ｐ〈０．０５，Ｐ〈０．０１），心房、心室肌心肌纤维细胞核及肌原纤维大量糖原沉着，肌丝溶解，可见髓样小体形成，线粒体变性、胶原纤维增多等超微结构改变。     

应用微电极阵列记录技术研究抑郁大鼠整体心脏心肌电生理特性

目的研究慢性应激对抑郁大鼠心房、心室场电位时程(FAPD)的影响。方法随机将20只大鼠分为对照组、抑郁组,对抑郁组大鼠进行连续21天的慢性应激。应用微电极阵列技术(MEA)记录心房、心室肌场电位波形、心房、心室FAPD。结果抑郁组大鼠慢性应激后的糖水消耗试验、自主活动得分均明显低于对照组(P<0.01)。MEA记录技术可以记录到60个位点心房、心室肌FAPD不同的波形;抑郁组大鼠心房FAPD高于对照组(83.14±4.61msvs45.76±3.66ms,P<0.05)。两组心室肌FAPD无差异。结论慢性应激所致的抑郁可明显延长大鼠心房FAPD,这可能是抑郁导致心律失常的机制之一。     

正常及顿抑心肌组织CGRPmRNA原位杂交研究

在大鼠心肌顿抑模型上采用原位杂交技术观察了正常及顿抑心肌组织降钙素基因相关肽（ Ｃ Ｇ Ｒ Ｐ）ｍ Ｒ Ｎ Ａ 表达的情况。结果发现正常心房及心室肌组织中存在 Ｃ Ｇ Ｒ Ｐｍ Ｒ Ｎ Ａ,心脏的血管周围也有分布。顿抑心肌组织中 Ｃ Ｇ Ｒ Ｐ ｍ Ｒ Ｎ Ａ 阳性表达显著减弱。     

血管紧张素Ⅱ对心肌缝隙连接蛋白43重构的影响及贝那普利的干预作用

目的采用大鼠肾上腹主动脉部分结扎的模型,观察心肌缝隙连接蛋白（Connexin,Cx）43含量和分布的变化以及贝那普利干预的防治效果。方法将30只雄性Wistar大鼠随机等分为对照组（A组）、腹主动脉结扎组（B组）、结扎+贝那普利组（C组）。喂养8周后处死,用放射免疫法测定血浆血管紧张素Ⅱ（AngⅡ）浓度和心肌组织AngⅡ浓度,用免疫组化方法显示大鼠心肌Cx43的分布特征,半定量统计分析。结果与A组相比,B组大鼠血浆、心肌AngⅡ浓度显著升高（均P<0.01）,但B组大鼠心房肌及心室肌Cx43含量均较A组显著减少（分别为P<0.05和P<0.01）,且分布紊乱;而C组Cx43含量较B组显著增多（P<0.01）,且分布不规律程度减轻。结论AngⅡ升高可能导致心肌Cx43重新分布及表达减少;贝那普利能有效减轻Cx43的重构。     

自发性高血压大鼠心脏NPY、CGRP、SP、VIP样神经纤维分布状况的免疫组织化学研究

目的了解自发性高血压大鼠（ＳＨＲ）心脏各部含神经肽Ｙ（ＮＰＹ）、含降钙素基因相关肽（ＣＧＲＰ）、含Ｐ物质（ＳＰ）和含血管活性肠肽（ＶＩＰ）神经纤维的变化，探讨它们与某些心血管病的关系。方法对１０只ＳＨＲ大鼠及８只京都Ｗｉｓｔａｒ大鼠（ＷＫＹ）心脏各部四种肽能神经纤维进行了免疫组化ＡＢＣ法对比观察。结果ＳＨＲ大鼠心房肌、心室肌、冠状动脉系统和心瓣膜ＮＰＹ样神经纤维分布密度和膨体密度趋于增加，对心血管的支配增强。而ＣＧＲＰ样、ＳＰ样和ＶＩＰ样神经纤维分布密度和膨体密度趋于减低，对心血管的支配减弱。结论四种神经肽可能与高血压病及冠心病的发病机理有密切关系，可能参与心脏及其冠脉血管的生理调节和病理过程。     

支气管哮喘大鼠肺内非肾上腺素能非胆碱能神经分布及神经肽含量的相关性研究

目的探讨支气管哮喘（简称哮喘）大鼠肺内非肾上腺素能非胆碱能（non—adrenergicnon—cholinergic,NANC）神经分布及其神经肽含量的变化并分析两者的相关性。方法20只Wister大鼠随机分成正常组和哮喘组。采用免疫组织化学和计算机图象分析观察大鼠肺内降钙素基因相关肽（calcitoningene-relatedpeptide,CGRP）和血管活性肠肽（vasoactiveintestinalpeptide,VIP）免疫反应阳性纤维的变化,并且用酶联免疫吸附试验法测定肺泡灌洗液中CGRP和VIP的浓度。结果①哮喘大鼠肺内CGRP和VIP阳性纤维的分布和密度均发生了显著的变化,CGRP阳性纤维显著增多,染色加深,相对阳性染色面积和光密度值,与对照组相比,差异有统计学意义（P〈0．01）;VIP阳性纤维明显缺乏,相对阳性染色面积和光密度值,与对照组相比,差异有统计学意义（P〈0．05或P〈0．01）。②哮喘大鼠肺泡灌洗液中CGRP的浓度与正常对照组相比显著增高（P〈0．01）,与CGRP阳性纤维的相对染色面积（r=0．903）和光密度值（r=0．880）呈正相关;VIP的浓度显著降低（P〈0.01）,与VIP阳性纤维的相对染色面积（r=0．899）和光密度值（r=0．878）呈正相关。结论哮喘大鼠肺内NANC神经分布异常,这可能是导致相应的神经肽含量变化的直接原因。     

支气管哮喘大鼠肺内非肾上腺素能非胆碱能神经分布及其神经肽含量的相关性研究

目的 探讨支气管哮喘(简称哮喘)大鼠肺内非肾上腺素能非胆碱能(non-adrenergic non-cholinergic,NANC)神经分布及其神经肽含量的变化并分析两者的相关性.方法 20只Wister大鼠随机分成正常组和哮喘组.采用免疫组织化学和计算机图象分析观察大鼠肺内降钙素基因相关肽(calcitonin gene-related peptide,CGRP)和血管活性肠肽(vasoactive intestinal peptide,VIP)免疫反应阳性纤维的变化,并且用酶联免疫吸附试验法测定肺泡灌洗液中CGRP和VIP的浓度.结果 ①哮喘大鼠肺内CGRP和VIP阳性纤维的分布和密度均发生了显著的变化,CGRP阳性纤维显著增多,染色加深,相对阳性染色面积和光密度值,与对照组相比,差异有统计学意义(P＜0.01);VIP阳性纤维明显缺乏,相对阳性染色面积和光密度值,与对照组相比,差异有统计学意义(P＜0.05或P＜0.01).②哮喘大鼠肺泡灌洗液中CGRP的浓度与正常对照组相比显著增高(P＜0.01),与CGRP阳性纤维的相对染色面积(r=0.903)和光密度值(r=0.880)呈正相关;VIP的浓度显著降低(P＜0.01),与VIP阳性纤维的相对染色面积(r=0.899)和光密度值(r=0.878)呈正相关.结论 哮喘大鼠肺内NANC神经分布异常,这可能是导致相应的神经肽含量变化的直接原因.     

Noradrenergic hyperinnervation in the heart of stroke-prone spontaneously hypertensive rats (SHRSP).

Noradrenergic (NA) nerve fiber density was investigated in the subepicardium and myocardium of ventricles in stroke-prone spontaneously hypertensive rats (SHRSP) and was compared with that of normotensive Wistar Kyoto (WKY) rats. Fluorescent NA nerve fibers in the subepicardium of the right and left ventricles of both strains at the ages of 10, 30, 60, 90, and 180 days were examined by the glyoxylic acid method. NA nerve fibers in the myocardium of the right and left ventricles and the ventricular septum of both strains at the ages of 30, 90, and 180 days were also examined in a similar manner. The density of NA nerve fibers was measured by quantitative image analysis. The distribution pattern of NA nerve fibers in the entire subepicardium of ventricles of both strains showed a meshwork pattern throughout the examination period. In sections of the myocardium, NA nerve fibers were distributed between heart muscle cells and around blood vessels in both strains at all ages examined. The densities of NA nerve fibers in the subepicardium of the ventricles of SHRSP were significantly higher than those of WKY rats at all ages examined except for the subepicardium of the left ventricle at 90 days of age. The densities in the myocardium of the right ventricle in 30- and 90-day-old SHRSP were significantly higher than those in WKY rats. The ratios of NA nerve fiber density of SHRSP to that of WKY rats were greater in the subepicardium of the right and left ventricles, except at 90 days of age, and in the myocardium of the right ventricle of younger animals as compared with older ones. NA hyperinnervation in the subepicardium and myocardium of the ventricles of SHRSP may be a primary change of the heart before the onset of hypertension and may be caused by hyperfunction of the stellate ganglia.     

Effects of Several Denervation Procedures on Distribution of Calcitonin Gene-Related Peptide and Substance P Immunoreactive in Rat Stomach

The effect of chemical deafferentation, vagotomy(VGX), and gangliosympathectomy (GSX) on the density offibers containing calcitonin gene-related peptide (CGRP)and substance P (Sub.P) in the rat gastric wall was studied. Chemical deafferentation bycapsaicin abolished the density of CGRP-immunoreactive(IR) fibers, not Sub.P-IR fibers. Ten days after VGX,the density of CGRP-IR or Sub.P-IR fibers in the mucosa was largely reduced, while no reductionof CGRP-IR and Sub.P-IR fibers was seen in submucosaland muscular layers. GSX significantly reduced thedensity of CGRP-IR fibers in the mucosa and caused a moderate decrease in the fibers in submucosaland muscular layers. Pretreatment with6-hydroxydopamine, a neurotoxin for noradrenergicnerves, did not affect the density of CGRP-IR fibers inthe gastric wall. The density of Sub.P-IR fibers in thegastric wall was not affected by GSX. These studiesindicate that the CGRP-IR and Sub.P-IR fibers in themucosa are susceptible to extrinsic nerve denervation compared with those in the submucosa and musclelayers, that a major portion of the CGRP-IR fibers inthe mucosa is of both vagal and spinal origin, and thata major portion of the Sub.P-IR fibers in the mucosa is of vagal origin. Furthermore, thepresent results support that CGRP-IR fibers, notSub.P-IR fibers, in the rat stomach arecapsaicin-sensitive.     

Expression of cardiac calcium regulatory proteins in atrium v ventricle in different species.

The duration of contraction in isolated electrically driven preparations from atrium and ventricle of mouse, rat, rabbit, guinea-pig and dog was consistently shorter in atrial compared to ventricular preparations. Overexpression of phospholamban (PLB) in transgenic mice prolonged duration of contraction, underscoring the importance of PLB for kinetics of cardiac contractility. The expression of regulatory proteins was studied by Western and Northern blot analysis. In rat myocardium, expression of the sarcoplasmic reticulum Ca2+ ATPase (SERCA) was higher in atrium than in ventricle, as was also observed in the rabbit, guinea-pig and wild-type mouse samples. Canine myocardium, however, had similar levels of SERCA (protein and mRNA) in atrium and ventricle. PLB and calsequestrin on protein and RNA levels were lower in atrium than in ventricle from rat, rabbit, guinea-pig and wild-type mouse. PLB protein and RNA levels were higher in ventricle than in atrium at ages 1 and 5 days postnatally and in adult rats. SERCA protein and RNA levels were higher in ventricle than in atrium at days 1 and 5 after birth, but lower in ventricle than in atrium in adult rats. In dog, the calsequestrin level was identical in atrium and ventricle (protein and mRNA) and PLB did not differ between atrium vs ventricle at the protein level but was lower at the mRNA level. Also, Ca2+ uptake was higher in atrium than in ventricle in the dog samples. The expression of the inhibitory subunit of troponin was unchanged between atrium and ventricle in all species studied (protein and mRNA). In dog, protein expression of triadin and junctin was lower in atrium vs ventricle. Triadin mRNA was not altered in dog atrium vs ventricle. In summary, while the hastened relaxation of atrium vs ventricle correlates in part with the lower expression of PLB and higher expression of SERCA, altered regional expression of other SR proteins handling Ca2+ may also play an important role in some species.     

Isomyosin distribution in normal and pressure-overloaded rat ventricular myocardium. An immunohistochemical study

We have used affinity-purified antibodies reacting with guinea pig soleus muscle and ventricular myosin heavy chains to analyze the distribution of specific isomyosin in the ventricular myocardium of normal and renal hypertensive rats. Immunofluorescent staining of cardiac tissue sections with the two antimyosins revealed striking variations in reactivity among ventricular muscle fibers, reactive fibers being more numerous in the left compared to the right ventricle and in subendocardial compared to subepicardial layers. The response of the ventricular myocardium changed during development: all fibers were stained in the newborn rat, whereas most fibers were unreactive in 1-month-old animals. The number of reactive fibers increased again in subsequent stages leading to a mixed pattern in adult animals. The normal mixed pattern of reactivity was transformed into a uniformly positive pattern in hypertensive rats 2 months after surgery. This complete transformation was observed in 20 out of 23 hypertensive animals examined. These findings indicate that the two antimyosins cross-react with a particular type of ventricular myosin heavy chain, whose distribution varies in different muscle cells and whose relative concentration changes during development and during cardiac hypertrophy induced by systemic hypertension. We suggest that differences in pressure load may be responsible for both regional variations in isomyosin distribution and for isomyosin changes in hypertensive animals.     

Histological study on the distribution of autonomic nerves in the human heart

 To investigate the distribution of autonomic nerves in the human heart, six autopsied hearts without cardiovascular disease were studied by a histochemical method for acetylcholinesterase (AChE) and by an immunohistochemical method for tyrosine hydroxylase (TH). The density of nerve distribution was microscopically calculated by the point-counting method to evaluate regional distribution of the autonomic nerves. There were more AChE-positive nerves and TH-positive nerves in the atrium than in the ventricle, and more at the base than at the apex in the ventricle. There were more AChE-positive nerves in the subendocardial area than in the subepicardial area of the myocardium. In the atrium, AChE-positive nerves were more numerous than TH-positive nerves. On the other hand, there were more TH-positive nerves than AChE-positive nerves in the ventricle. Predominancy of the distribution density at the anterior to the posterior wall of the ventricle was observed for TH-positive nerves. The different distribution patterns of sympathetic and parasympathetic nerves could modify cardiac performance under both physiologic and pathologic conditions. Received: July 8, 2002 / Accepted: October 12, 2002 Present address: Third Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan Tel. +81-95-849-7288; Fax +81-95-849-7290 Correspondence to H. Kawano     

Effect of vagotomy on expression of neuropeptides and histamine in rat oxyntic mucosa

The effect of vagotomy and pyloroplasty on the density of nerve fibers containing bombesin/gastrin-releasing peptide (GRP), calcitonin gene-related peptide (CGRP), and galanin as well as histamine-, 5-hydroxytryptamine (5-HT)-, and somatostatin-containing cells in the oxyntic mucosa of the rat stomach was studied. Ten days after vagotomy and pyloroplasty the density of histamine-containing cells in the oxyntic mucosa was increased by 70% (P<0.05), and these cells were larger and showed more extensive cell processes than in control animals. The density of 5-HT-immunoreactive (IR) cells and somatostatin-IR cells were not affected. A marked decrease in the density of CGRP-IR nerve fibers and a slighter decrease in the density of GRP-IR nerve fibers was observed in the mucosal layer, while only a minor reduction of CGRP-IR fibers, and no reduction of GRP-IR fibers was seen in the muscular layer. The density of galanin-IR nerve fibers was not affected. The height of the oxyntic mucosa was reduced by about 25% (P<0.05). Thus, a striking effect on the histamine-IR cells was seen, supporting the view that these cells are regulated by the vagus nerve. The study also indicates that a major portion of the CGRP-IR nerve fibers, and part of the GRP-IR nerve fibers, in the mucosal layer of the fundic region are of vagal origin or regulated by normal vagus nerve activity.This study was supported by the Medical Research Council of the Academy of Finland.     

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。     

Analysis of mast cells and myocardial fibrosis in autopsied patients with hypertensive heart disease

ObjectiveTo analyze the percentage of collagen fibers and mast cell density in the left ventricular myocardium of autopsied patients with and without hypertensive heart disease.MethodsThirty fragments of left ventricular myocardium were obtained from individuals autopsied at the Clinical Hospital of the Federal University of Triângulo Mineiro (UFTM) in the period from 1987 to 2017. Individuals were divided into two groups: those with hypertensive heart disease (HD) and those with no heart disease (ND). Subjects were also assessed according to age, gender and race (white and non-white). Collagen fibers were quantified by computed morphometry and mast cell density was assessed by immunohistochemical methods.ResultsThere were significantly more collagen fibers in the left ventricle in the HD group than in the ND group (p< 0.001). Mast cell density was significantly higher in the left ventricle of individuals with HD immunolabeled with anti-chymase and anti-tryptase antibodies (p=0.02) and also of those immunolabeled only with anti-tryptase antibodies (p=0.03). Analyzing the HD group, there was a significant positive correlation between the percentage of collagen fibers in the left ventricle and mast cell density immunolabeled by anti-chymase and anti-tryptase antibodies (p=0.04) and also mast cell density immunolabeled only with anti-tryptase antibodies (p=0.02).ConclusionsMast cells are involved in the development of hypertensive heart disease, contributing to the remodeling of collagen fibers in this disease.