链霉素对缺氧大鼠右心室肥大及c—myc原癌基因表达的影响

本文观察了非选择性阳离子通道阻断剂链霉素（在脊椎动物心肌阻断牵张激活的钠离子跨膜内流）对缺氧大鼠右心室肥大和缺氧大鼠心肌中ｃ－ｍｙｃ基因表达的影响。结果如下：（１）急性缺氧时，右心室收缩压明显增高，慢性间断性缺氧进一步增高右心室收缩压并明显增高右心室重量指数。（２）链霉素对急性缺氧性肺动脉增压反应无影响。但可明显降低慢性缺氧大鼠右心室收缩压和右心室重量指数。（３）缺氧引起右室心肌迅速一过性的ｃ－ｍ     

甲基叔丁基醚对原癌基因和功能基因表达的影响

甲基叔丁基醚（ＭＴＢＥ）是一种新型的汽油添加剂,被用来提高汽油燃烧效率,减少汽车尾气中有害物质的排放。ＭＴＢＥ具有一定的动物致癌性,但其机制目前并不清楚。本研究采用免疫组织化学方法,检测了ＭＴＢＥ对体外培养的ＮＩＨ３Ｔ３细胞中ｃ－ｍｙｃ和ｐ２１蛋白表达的影响;采用点杂交方法,从ＲＮＡ水平检测了ＭＴＢＥ亚慢性染毒大鼠肝组织中原癌基因ｃ－ｍｙｃ基因和功能基因ＧＳＴ－Ｐ基因的表达情况。免疫组化结果显示,ＭＴＢＥ可诱导ｃ－ｍｙｃ基因的高表达,对ｐ２１蛋白的表达未见明显影响。点杂交结果显示,ＭＴＢＥ可明显诱导大鼠肝组织中ｃ－ｍｙｃ基因的高表达,而对ＧＳＴ－Ｐ基因的表达未见明显影响。上述结果提示,ＭＴＢＥ可诱导细胞中ｃ－ｍｙｃ基因表达活性增高,可能是其动物致癌性的机制之一。     

上皮性卵巢肿瘤C—myc与p53蛋白的表达及意义

用免疫组化ＬＳＡＢ方法检测５例正常卵巢组织和３５例卵巢肿瘤组织中的Ｃ－ｍｙｃ（原癌基因）和ｐ５３（抑癌基因）蛋白的表达水平。结果从良性卵巢腺瘤、交界性到恶性卵巢囊腺癌，Ｃ－ｍｙｃ和ｐ５３阳性表达呈增高趋势。其阳性表达率与卵巢肿瘤的细胞增殖状态、肿瘤分化及临床分期有关。检测卵巢肿瘤中Ｃ－ｍｙｃ及ｐ５３基因表达可了解卵巢囊腺癌的发生、发展，找出原癌基因及抑癌基因表达与卵巢瘤生物学行为间的关系。     

Bcl-2、c-myc基因在急性白血病中的表达及其意义

为探讨凋亡调控基因ｂｃｌ－２、ｃ－ｍｙｃ对白血病的发生、疗效及预后判定的意义,采用免疫组化法检测ｂｃｌ－２、ｃ－ｍｙｃ在７２例急性随系白血病患者骨髓细胞中的表达。结果发现初治和复发者ｂｃｌ－２、ｃ－ｍｙｃ的表达比完全缓解组和对照组明显增高（Ｐ〈０．０１％）;初治组和复发组之间差异无显著性（Ｐ〉０．０５）;ｂｃｌ－２与ｃ－ｍｙｃ的表达呈正相关（Ｐ〈０．０１）;ｂｃｌ－２和／或ｃ－ｍｙｃ高度表达的患者     

钙通道阻滞剂对缺氧大鼠右心室心肌CnAβmRNA及血浆NO、iNOS、ET-1水平的影响

目的通过研究钙通道阻滞剂对缺氧大鼠右心室心肌钙调神经磷酸酶Aβ(CnAβ)mRNA及血浆NO、一氧化氮合酶(iNOS)、内皮素-1(ET-1)水平的影响,进一步探讨钙通道阻滞剂防治慢性缺氧致右心室肥大的机制。方法实验大鼠分为3组,采用配伍组设计,每组各10只,即正常组、缺氧组、苯磺酸氨氯地平(Norvasc)处理组(灌喂Norvasc 30 mg.kg-1.d-1),后2组置于氧浓度为(10.0±0.5)%的大型玻璃舱中,持续缺氧21 d。第21天处死大鼠,采血测NO、iNOS、ET-1的水平,分离心脏称质量,并留右心室测CnAβmRNA的表达。结果⑴缺氧组右室与左室加室间隔的重量比、右室重量与体重之比均明显高于正常组和处理组(P<0.01)。⑵缺氧组右心室心肌CnAβmRNA的表达明显高于正常组和处理组(P<0.01)。⑶缺氧组血浆NO、iNOS水平明显低于正常组和处理组(P<0.01),ET-1水平则明显高于正常组和处理组(P<0.01)。结论钙通道阻滞剂-Norvasc能够抑制慢性缺氧右心室肥大,也可能与调节血浆NO、iNOS、ET-1水平,改善肺动脉压力,下调CnAβmRNA的表达有关。     

饮茶对香烟中特异性亚硝胺－NNK诱发小鼠肺癌基因表达的影响

通过研究饮茶对香烟中特异性亚硝胺－ＮＮＫ诱发小鼠肺癌基因表达的影响，对饮茶可拮抗香烟致癌作用的结果做进一步验证，并对其作用机理进行探讨。所使用方法为国内外尚属新的技术，即非同位素标记探针测定基因表达。其结果表明阳性小鼠给ＮＮＫ４周后，ｃ－ｍｙｃ和ｃ－ｒａｆ基因表达水平明显增高，而小鼠若同时饮绿茶则可抑制这种增高，抑制率达５０％和２０％，到第８周时阳性对照组的ｃ－ｍｙｃ和ｃ－ｒａｆ基因水平恢复正常。与此相对应，ｃ－Ｈ－ｒａｓ基因在第８周时表达增高，约为阴性组３倍，饮茶对此同样有抑制作用，抑制率为５０％。在第２、４和８周均未见阳性对照组ｖｓｉｓ基因表达水平的改变。     

饮茶对香烟中特异性亚硝胺－NNK诱发小鼠肺癌基因表达的影响

通过研究饮茶对香烟中特异性亚硝胺－ＮＮＫ诱发小鼠肺癌基因表达的影响，对饮茶可拮抗香烟致癌作用的结果做进一步验证，并对其作用机理进行探讨。所使用方法为国内外尚属新的技术，即非同位素标记探针测定基因表达。其结果表明阳性小鼠给ＮＮＫ４周后，ｃ－ｍｙｃ和ｃ－ｒａｆ基因表达水平明显增高，而小鼠若同时饮绿茶则可抑制这种增高，抑制率达５０％和２０％，到第８周时阳性对照组的ｃ－ｍｙｃ和ｃ－ｒａｆ基因水平恢复正常。与此相对应，ｃ－Ｈ－ｒａｓ基因在第８周时表达增高，约为阴性组３倍，饮茶对此同样有抑制作用，抑制率为５０％。在第２、４和８周均未见阳性对照组ｖｓｉｓ基因表达水平的改变。     

甲基叔丁基醚对大鼠肝组织基因表达的影响

目的甲基叔丁基醚（ＭＴＢＥ）是一种新型的汽油添加剂,动物试验显示其具有一定的致癌性。为了解其动物致癌性的可能机制,我们检测了经ＭＴＢＥ亚慢性染毒的大鼠肝组织中原癌基因ｃｍｙｃ基因和功能基因谷胱甘肽Ｓ转移酶Ｐ（ＧＳＴＰ）基因的表达情况。方法４０只雄性ＳＤ大鼠,体重１８０～２００ｇ,随机分为４组。将ＭＴＢＥ溶于适量豆油中,灌胃染毒,染毒剂量分别为２００ｍｇ／ｋｇ,６００ｍｇ／ｋｇ,１０００ｍｇ／ｋｇ和对照组。每天１次,每周５天,共１３周。动物肝组织于液氮速冻后,一步法提取总ＲＮＡ。随机引物法地高辛标记ｃｍｙｃ和ＧＳＴＰ探针,与ＲＮＡ进行点杂交,图像分析仪分析结果。结果大鼠肝组织中ｃｍｙｃ基因表达水平明显增高,ＧＳＴＰ基因表达未见增强。结论ＭＴＢＥ可明显诱导ｃｍｙｃ基因的高表达,提示其具有促进细胞增殖的作用,这是其动物致癌性的可能机制之一。     

镉对小鼠肢芽细胞增殖细胞核抗原和c—myc基因表达的影响

目的探讨镉对胚胎肢芽细胞增殖抑制的机制。方法运用免疫组化ＳＰ法结合图像分析技术观察了ＣｄＣｌ２对增殖细胞核抗原（ＰＣＮＡ）和ｃ－ｍｙｃ基因表达的影响。结果ＰＣＮＡ和ｃ－ｍｙｃ基因在正常增殖的胚胎肢芽细胞中均呈强阳性免疫反应；０．１～０．８μｇ／ｍｌＣｄＣｌ２对细胞中ＰＣＮＡ和ｃ－ｍｙｃ的表达均有明显的抑制作用，并呈现明显的剂量－效应关系。结论ＣｄＣｌ２可通过抑制ＰＣＮＡ和ｃ－ｍｙｃ的表达而对胚胎细胞增殖产生抑制作用。     

染料木黄酮对缺氧性肺动脉高压及右心室肥大的预防作用

目的:研究染料木黄酮(genistein,Gen)对慢性缺氧性肺动脉高压(HPH)的预防作用,为防治HPH提供一种新的途径。方法:健康雄性Wistar大鼠,体重(210.3±28.7)g,随机分为5组:①平原对照组(C);②慢性缺氧组(H);③缺氧+Gen低剂量组(H+L):25mg/kg bw;④缺氧+Gen中剂量组(H+M):50mg/kg bw;⑤缺氧+Gen高剂量组(H+H):100mg/kg bw;C组在平原,②～⑤组每天灌胃大鼠受试物或与受试物等容积的二甲基亚砜(DMSO),置于减压舱,模拟海拔5000m高原,8h/d,持续21d,分别测定肺动脉压、右心室功能和右心室肥大指数。结果:Gen可以显著抑制慢性缺氧引起的肺动脉压升高(P<0.01)。单纯缺氧组右心室肥大指数RV/(LV+Sep)显著增加(P<0.01);与单纯缺氧组比较,Gen各组RV/(LV+Sep)从低剂量到高剂量呈逐渐降低的趋势(40.53±3.80)%,(39.07±3.69)%,(33.73±3.20)%,但仅高剂量组(100mg/kg bw)有显著性差异(P<0.01)。结论:Gen可以有效防治慢性缺氧性肺动脉高压,对慢性缺氧诱导的右心室肥大的预防作用与剂量有关,其作用机制有待进一步探讨。     

Left ventricular hypertrophy and skin color among American blacks.

The association between skin color, a measure of black-white genetic admixture, and left ventricular hypertrophy was examined in 551 black men and women, from three US cities, who underwent electrocardiography and skin reflectance measurements during 1972-1974. The overall prevalence of left ventricular hypertrophy (Minnesota Code 3-1 or 3-3) was 14% (18% in men; 11% in women). Left ventricular hypertrophy was strongly associated with systolic (p less than 0.001) and diastolic (p = 0.001) blood pressure, but less so with skin color (p = 0.09) [corrected]. The prevalence of left ventricular hypertrophy was 16% in the darkest versus 12% in the lightest quartile of skin color. In a multiple logistic regression model, adjusting for systolic blood pressure and blood pressure medication use, the relation between left ventricular hypertrophy and skin color was insignificant (p = 0.18); the odds ratio of having left ventricular hypertrophy in dark (75th percentile of skin color) versus light (25th percentile) skinned blacks after adjustment for systolic blood pressure, systolic blood pressure medications, age, and sex was 1.2 (95 percent confidence interval 0.8-1.8). Overall, the association between left ventricular hypertrophy and skin color was weak and not statistically significant, suggesting that black individuals do not have a genetic susceptibility to the effects of blood pressure on the myocardium. We did not postulate any significant effect modification of this association by sex. However, the data suggest that the association between skin color and left ventricular hypertrophy may be different between men and women.     

Mechanical properties of the copper-deficient rat heart

Copper deficiency is known to induce cardiac hypertrophy, cardiac morphologic lesions and altered electrocardiograms. These findings suggest that copper deficiency may also influence the mechanical properties of the myocardium. In the present study, weanling albino rats were fed a copper-deficient (-Cu) diet and compared to rats fed the same diet but with copper supplementation in the drinking water (+Cu). Rats were studied during a 1-week period following 4.5-5.5 weeks of treatment. When compared to +Cu rats, the -Cu rats exhibited characteristic signs of copper deficiency, such as reduced body weight, hypoceruloplasminemia, depressed hematocrit, low copper and elevated iron concentration in the liver. The -Cu rats also exhibited cardiac hypertrophy and both a dilution and depletion of left ventricular norepinephrine. Hearts were perfused and paced at both 27 degrees and 37 degrees. When compared to hearts from +Cu rats, the -Cu hearts: 1) had lower spontaneous heart rates, 2) had decreased coronary resistance, 3) gained significant weight during perfusion, 4) consumed more oxygen per unit pressure developed, and 5) developed less systolic pressure with a reduced rate of pressure development. However, the time to peak pressure development, one-halt relaxation time, and refractory period were not affected. The altered characteristics of the copper-deficient myocardium may be due to changes in the elastic properties of the muscle, aberrant energy metabolism or norepinephrine depletion.     

Time course and progression of pressure overload-induced cardiac hypertrophy in rats

AIM: To study the time course and progression of pressure overload-induced left ventricular hypertrophy METHODS: Left ventricular hypertrophy was induced in rats by abdominal aorta constriction and assessed at different time points (10, 15, 20, 25, 35, and 45 days) after operation. RESULTS: The cardiac index (the ratio of heart weight to body weight) in aortic-banded animals was characterised by phasic changes when compared with the sham operated and the control animals. In aortic-banded rats the cardiac index rose sharply at days 10 and 15 after operation. This sharp increase was followed by a phase of slight increase (day 20), and then it again sharply increased (day 25). At the remaining time points (days 35 and 45) the cardiac index was significantly increased in comparison with that of the sham operated and the control animals but the increase diminished gradually. CONCLUSION: Our results suggest that left ventricular hypertrophy develops not in a linear but in a phasic way. Yet, the experimental model we used produced a relatively stable left ventricular hypertrophy.     

容量超负荷诱导大鼠心脏营养素-1和血管紧张素Ⅱ含量的变化

目的 观察慢性容量超负荷在诱导大鼠心肌肥大模型中心肌组织中CT-1和Ang Ⅱ含量的变化,进而探讨其可能机制.方法 将SD大鼠随机分为正常组,伪手术组和容量负荷模型组,分别测量全心室重/体重比值、右心室重/体重比值和平均动脉压,检测血浆中肾素活性和Ang Ⅱ含量,右心室的组织切片进行免疫组织化学检测.结果 模型组与正常对照组及伪手术组比较心肌明显肥大且升高150％ (P＜ 0.01).平均动脉压模型组或伪手术组与正常组比较差异均无统计学意义(P＞0.05);血浆肾素活性模型组与伪手术组比降低(P＜0.01),血浆Ang Ⅱ含量模型组与伪手术组比升高(P＜0.01);右心室CT-1免疫组化模型组与伪手术组的表达升高(P＜0.05).结论 慢性容量超负荷可诱导大鼠心肌肥大,AngⅡ和CT-1可能是参与容量超负荷诱导心肌肥大反应的重要因素.     

Effect of a carbohydrate supplement on feeding behaviour and exercise in rats exposed to hypobaric hypoxia

The effect of a carbohydrate supplement, offered as a diet option, on feeding behaviour, body weight gain, and endurance exercise was studied in rats exposed to hypobaric hypoxia. Male albino rats (n = 35) were randomly divided into 5 groups; hypoxic supplemented and control groups; normoxic supplemented and control groups, and an untreated control group. After treadmill training for 5 days, the hypoxic groups were exposed to simulated high altitude equivalent to 6960 m for 18 days continuously. Food and water intakes, body weight and endurance exercise were recorded before and during the exposure period. Blood glucose, insulin, muscle and liver glycogen were assayed at the end of the exposure period. Hypobaric hypoxia resulted in a significant decrease in food and water intake, and body weight, and reduced endurance exercise capacity compared to the basal and normoxic group values. The carbohydrate supplement did not ameliorate the hypoxia-induced loss in body weight, but however, significantly delayed the onset of fatigue during exercise in the supplemented rats compared to the hypoxic control group.     

Blood pressure and urinary cations in urban Bantu of Zaire

The 24-hour urinary excretion of sodium, potassium, calcium, and magnesium and their relationship to arterial blood pressure were investigated from December 1983 to May 1984 in a 10% random sample (n = 666) of urban Bantu of Kinshasa, Za?re. In youths aged 10-19 years, blood pressure averaged 109/60 mmHg, and the 24-hour urinary excretion of sodium, potassium, calcium, and magnesium averaged 84 mmol, 30 mmol, 483 mumol, and 2 mmol, respectively. After adjustment for age and body weight, a weak positive association became apparent between diastolic pressure and the urinary sodium to potassium ratio in girls and all youths. In adults aged greater than or equal to 20 years, blood pressure averaged 124/72 mmHg, and the 24-hour urinary excretion of sodium, potassium, calcium, and magnesium averaged 87 mmol, 33 mmol, 828 mumol, and 1.88 mmol, respectively. After adjustment for sex, age, body weight, and pulse rate in all adults, systolic pressure was significantly and positively correlated with urinary sodium excretion and negatively correlated with urinary potassium excretion, while diastolic pressure was weakly associated with urinary calcium excretion. In women, an independent and significant association was also observed between systolic pressure and 24-hour urinary sodium. When instead of the 24-hour urinary excretion of sodium and potassium, the sodium to potassium ratio was considered as an independent variable in multiple regression analysis, both systolic and diastolic pressure were independently and positively related to the sodium to potassium ratio in all adults. These results indicate that in this urban Bantu population, age and body weight are the major predictors of systolic pressure in youths and the major predictors of both systolic and diastolic pressure in adults. The sodium to potassium ratio did contribute to the prediction of blood pressure in girls and when, in youths as well as in adults, both sexes were considered together. Urinary calcium was associated with diastolic pressure only in all adults.     

Naringin Improves Diet-Induced Cardiovascular Dysfunction and Obesity in High Carbohydrate,High Fat Diet-Fed Rats

Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day) improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats.     

Effects of mercury on the contractile activity of the right ventricular myocardium

The increase in right ventricular systolic pressure observed in vivo after the administration of mercury opposes to the idea that the metal depresses the cardiac pump performance. We then investigated the effects of HgCl₂ (0.1 to 2.5 μM) on the contractile activity of the right ventricular myocardium, measuring isometric and tetanic contractions of right ventricular isolated strips, right ventricular isovolumic systolic and diastolic pressures, and the coronary perfusion pressure (0.03 to 3 μM) in constant-flow Langendorff-perfused rat hearts. The results presented here suggest that the acute effects of mercury on the right ventricular myocardium are distinct. When isolated strips of right ventricular wall are used, the contractile depression produced by mercury is manifested. However, when mercury is administered to isolated perfused hearts or in vivo this depressant effect is not revealed. The possible reasons for this behavior are the increased coronary perfusion pressure, which promotes a positive inotropic effect, manifested during the infusion of increasing concentrations of mercury, or the putative stretch of the ventricular fibers, which might cause the increment of diastolic pressure. An interesting finding is that the mechanical activity of the preparations, in which mercury is administered via coronary circulation, is not depressed and, even more, it can increase systolic pressure. However, the nature of this protective effect of coronary circulation cannot be explained by the results presented here. Received: 6 November 2000/Accepted: 27 April 2001     

Atorvastatin improves sodium handling and decreases blood pressure in salt-loaded rats with chronic renal insufficiency

ObjectiveOxidative stress and inflammation seem to mediate the cardiovascular risks associated with salt sensitivity. Because hydroxymethyl glutaryl coenzyme A reductase inhibitors decrease oxidation and increase nitric oxide (NO) synthesis, we examined the effects of atorvastatin (ator) on tissue injury in rats with a reduced renal mass produced by 5/6 nephrectomy. This salt-sensitive hypertension model causes kidney and cardiovascular injuries.MethodsAfter undergoing 5/6 nephrectomy or sham surgery, male Sprague–Dawley rats were randomized into five groups: sham, reduced renal mass and a normal salt diet (NNaD), NNaD+ator (50 mg · kg^?1 · d^?1), reduced renal mass and a high salt diet (HNaD), and HNaD+ator. After assessing the sodium balance for 7 d, we measured blood pressure (BP), creatinemia, proteinuria, nitrites, and 12(S)-hydroxy 5,8,10-heptadecatrienoic acid, the renal cortical expression of endothelial NO synthase, and the ratio of left ventricular weight to body weight.ResultsIn NNaD rats, creatinine, proteinuria, and 12(S)-hydroxy 5,8,10-heptadecatrienoic acid increased, renal NO indices decreased, but the Na⁺ balance, BP, and the left ventricular weight/body weight ratio remained unchanged. In the NNaD group, atorvastatin normalized the NO indices and decreased BP and proteinuria, although the remaining parameters continued unchanged. In contrast, HNaD increased creatinemia, proteinuria, and 12(S)-hydroxy 5,8,10-heptadecatrienoic acid excretion rates and decreased renal endothelial NO synthase. Salt retention was accompanied by increased BP and ventricular weight. In this HNaD group, atorvastatin prevented a BP increase, partly decreased sodium retention, but failed to improve NO indices, proteinuria, oxidant stress, and the left ventricular weight/body weight ratio.ConclusionAtorvastatin exerts beneficial effects on renal function, injury, and salt sensitivity in rats with a reduced renal mass on an NNaD. The HNaD hampers these beneficial effects.