Effect of captopril on myocardial energy metabolism in chronic pressure overload rats

Objective To investigate the effects of captopril on cardiac function and levels of energy-rich phosphates in pressure overload induced left ventricular hypertrophy rats. Methods One hundred and twenty SD rats were randomly divided into three groups： sham operation group （SH group, n=40）,coarctation of abdominal aorta group （CAA group, n=40） and captopril treatment lmg~ 100g1 ~ d-1） group （CAP group, n=40）. Left ventricular end-diastolic pressure （LVEDP）, left venh-icular mass index （LVMI）, levels of energy-rich phosphates and morphological changes of the myocardial mitochondria were compared at the 62 and 82 week after operation. Results At 62 week, in CAA group, LVMI and LVEDP were increased and _ dp/dtmax was decreased, while ATP and ADP were decreased and AMP was increased （P〈0.01）. These changes were much obvious at 8th week （P〈0.01）. Compared with those of CAA group, the parameters of heart function and energy-rich phosphates （ATP, ADP, AMP, TAN） in CAP group were improved significantly（P〈0.01） at the 6th and 8th week. In CAP group, the parameters of heart function and energy-rich phosphates （ADP, AMP, TAN） were much better at 8~ week than those at 6th week. The morphological change of mitochondria was less in CAP group than that in CAA group. Conclusion Captopril significantly improves myocardial energy metabolism in pressure overload rats and protects the function of myocardial mitochondria     

西洋参茎叶总皂苷对急性心肌梗死大鼠心肌能量代谢的影响

目的探讨西洋参茎叶总皂苷是否能改善缺血心肌细胞的能量代谢。方法选用急性心肌梗死模型大鼠,随机分为心悦胶囊大、中、小剂量组,倍他乐克组,模型组,同时设假手术及正常组(每组各8只)。药物治疗组于术后第2天开始灌胃给药,每日1次,术后第15天取心肌组织制成匀桨,采用高效液相色谱(HPLC)法测定心肌组织中ATP、ADP、AMP的含量,并计算总腺苷酸(TAN)含量及能荷(EC)值。结果心悦胶囊治疗组ATP的含量及EC水平均高于模型组,其中心悦胶囊大剂量组ATP的含量及心悦胶囊大、中、小剂量组的EC水平升高显著(P<0.05)。结论西洋参茎叶总皂苷能提高缺血心肌组织中ATP含量及EC的贮备水平。     

曲美他嗪对慢性心力衰竭大鼠心肌能量代谢及超微结构的影响

目的研究曲美他嗪对异丙肾上腺素诱导的慢性心力衰竭大鼠心肌能量代谢和超微结构的影响。方法72只雄性SD大鼠随机分为对照组(14只)和模型组(58只),模型制备采用皮下多点注射异丙肾上腺素法,4周后模型组大鼠死亡12只,再将存活的46只模型组大鼠随机分为未治疗组(M组,16只)、曲美他嗪治疗组(T组,15只)和培哚普利治疗组(P组,15只)。治疗5周后行二维心脏超声检查和病理形态学观察,并测定心肌组织能量代谢相关指标。结果与M组比较,T组大鼠LVEF、左心室短轴缩短率均提高;光镜和电镜下观察T组和P组心肌损伤程度较M组明显减轻。T组与P组大鼠心肌二磷酸腺苷(ADP)、一磷酸腺苷、ATP/ADP和总腺苷含量与对照组比较差异无统计学意义(P>0.05)。T组大鼠心肌肌浆网Ca2+-ATPase活性与对照组和P组比较差异无统计学意义。结论曲美他嗪能够改善心力衰竭大鼠心肌能量代谢、病理和超微结构,并且有改善大鼠心功能的趋势。     

小剂量卡托普利防治急性压力超负荷后大鼠心肌损伤的作用

目的 :探讨小剂量卡托普利防治急性压力超负荷大鼠心肌损伤的作用。方法 :腹主动脉部分缩窄法制作急性压力超负荷模型。 5 0只大鼠随机分为对照组、腹主动脉部分缩窄组和药物干预组。药物干预组给予卡托普利 30mg (kg·d)灌胃。分别测定各组大鼠心肌力学、心肌代谢酶活性、心肌血管紧张素Ⅱ (AngⅡ )含量及心肌超微病理分析。结果 :急性压力超负荷大鼠心肌超微结构出现明显缺氧性损伤 ,琥珀酸脱氢酶活性降低 ,收缩、舒张功能相对下降 ,心肌中AngⅡ含量显著升高。小剂量卡托普利可基本抑制压力超负荷大鼠心肌中AngⅡ的升高 ,显著减轻心肌的形态损伤、代谢酶活性降低和心肌收缩、舒张功能下降。结论 :小剂量卡托普利可有效防治急性压力超负荷导致的大鼠心肌损伤     

川芎嗪对压力超负荷大鼠心肌凋亡的干预作用

目的 :观察川芎嗪对压力超负荷大鼠心肌凋亡动态变化的影响。方法 :SD大鼠 ,缩窄腹主动脉建立压力超负荷模型 ;按缩窄与否随机分为手术组 （OG）、手术 +川芎嗪干预组 （OG+ TMP）和假手术组 （SOG）。采用脱氧核苷酸末端转移酶介导的缺口末端原位标记 （TUNEL ）法 ,检测心肌细胞凋亡指数 （CAI）。结果 :OG组与 OG+ TMP组各时间点的 CAI均高于 SOG组 （CAI为 0 ）。OG组与 OG+ TMP组相比较 ,OG+ TMP组的 CAI呈显著性降低趋势（多数 P<0 .0 5）。结论 :川芎嗪不能逆转压力超负荷大鼠的心肌凋亡 ,但有减缓心肌凋亡发生的趋势 ,具有心脏保护作用     

Myocardial energy metabolism in the hypertrophied hearts of spontaneously hypertensive rats

Summary Age-related changes in the myocardial energy metabolism were studied in spontaneously hypertensive (SHR) rats of 5–25 weeks of age. Systolic blood pressure increased rapidly during 5 to 10 weeks of age (developing phase) and attained a plateau level at 10 to 15 weeks (sustained phase). Even during the developing phase, the heart was hypertrophic, as assessed by an increase in the ratio of the ventricular weight to body weight. However, myocardial contents of glycolytic intermediates and high energy phosphate compounds and thus, the myocardial energy state (phosphorylation potential) in SHR rats did not differ from those in age-matched normotensive Wistar-Kyoto (WKY) rats. The lactate/pyruvate ratio was significantly lower in SHR rats. On the other hand, during the sustained phase, cardiac hypertrophy progressed only gradually, and myocardial contents of creatine phosphate and ATP were lower, while the lactate content was higher than in WKY rats. The lactate/pyruvate ratio was elevated, while phosphorylation potential was lowered. These findings suggest that the energy state is normal during the developing phase of hypertension despite the presence of cardiac hypertrophy and the increased pressure load, whereas the energy state is at a lower level during the sustained phase of hypertension.

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Zusammenfassung Die altersabhängigen Änderungen des myokardialen Energieumsatzes wurden bei spontanhypertensiven, 5 bis 25 Wochen alten Ratten (SHR) untersucht. Der systolische Blutdruck stieg zwischen der 5. und 10. Lebenswoche rasch an (Entwicklungsphase) und erreichte nach 10 bis 15 Wochen ein Plateau (Dauerphase). Auch während der Entwicklungsphase war das Herz hypertrophiert, gemessen an einem Anstieg des Verhältnisses Ventrikelgewicht: Körpergewicht. Jedoch unterschied sich der Gehalt des Myokards an Intermediärprodukten der Glykolyse und energiereichen Phosphaten und damit bezüglich des energetischen Status (Phosphorylierungspotential) bei SHR-Ratten nicht von gleichaltrigen normotensiven Wistar-Kyoto-Ratten (WKY). Das Lactat-Pyruvat-Verhältnis war bei SHR-Ratten signifikant vermindert. Andererseits nahm die Herzhypertrophie während der Dauerphase nur allmählich zu; der Gehalt an Kreatinphosphat und ATP war geringer, während der Lactatgehalt höher war als bei WKY-Ratten. Das Lactat-Pyruvat-Verhältnis war gesteigert, während das Phosphorylierungspotential vermindert war. Diese Befunde lassen vermuten, daß der energetische Status während der Entwicklungsphase der Hypertension normal ist trotz des Vorliegens einer Herzhypertrophie und gesteigerter Druckbelastung, während der energetische Status während der Dauerphase herabgesetzt ist.

     

艾司洛尔对紫绀型先天性心脏病患儿CPB过程中心肌损伤及能量代谢的影响

目的 探讨艾司洛尔对紫绀型先天性心脏病（CCHD）患儿体外循环（CPB）过程中心肌损伤的影响及机制.方法 将16例行CPB下心内直视术CCHD患儿随机分为观察组和对照组各8例,两组手术方法及麻醉方法均相同,但自麻醉诱导至术毕观察组和对照组分别静脉泵注艾司洛尔3 mg/（kg·h）及等量复方氯化钠溶液.观察两组手术一般情况,并分别于转流前（T1）、主动脉阻断后30 min（T2）、主动脉开放后30 min（T3）、术后24 h（T4）采集中心静脉血,测定肌酸激酶同工酶（CK-MB）、肌钙蛋白I（cTnI）水平,并于T1、T3取右心耳组织测定心肌组织腺甘酸含量及线粒体肿胀度（MSD）.结果 观察组复跳后心律失常发生率、多巴胺用量、ICU滞留时间及术后住院时间均显著小于对照组（P均〈0.05）;与T1时比较,两组T3和T4时血清CK-MB和cTnI水平明显升高、T3时心肌腺苷酸含量显著减少,MSD显著升高（P均〈0.01）,但观察组变化幅度均显著小于对照组（P〈0.05）.结论 艾司洛尔可通过改善心肌能量代谢及线粒体功能等途径减轻CCHD患儿CPB过程中缺血再灌注损伤.     

Effects of recurrent ischemia on myocardial high energy phosphate content in canine hearts

Summary Successive ischemic episodes are commonly seen in clinical and experimental cardiology. Although prolonged abnormalities of the canine myocardium have been described following a single ischemic episode, it is not known whether myocardial injury is cumulative following multiple ischemic episodes. Dogs were subjected to three 15-min left anterior descending coronary artery occlusions, each followed by 30 min of reperfusion.In vivo biopsies were obtained for biochemical analysis before and during the first occlusion and 30 min into each reperfusion period. ATP and creatine phosphate (CP) fell in the endocardium during occlusion by 24% and by 69% respectively (both p<.0001). While CP recovered during each reperfusion period, ATP remained significantly depressed. Loss of membrane-permeable purine nucleotide synthesis precursors occurred with the first reperfusion period but not with the second and third reperfusion periods. Therefore, reperfusion following one 15-min coronary occlusion is associated with severe depression of myocardial high energy phosphates; however, two additional occlusions do not cause a further decrease of these substances when intermittent reperfusion is allowed for 30 min.Supported in part by Grants HL 23140, 28048 and SCOR 26215 under the National Heart, Lung and Blood Institute, Bethesda, MarylandThis work was done during the tenure of Drs. Kloner and Ingwall as Established Investigators from the American Heart Association and with funds contributed in part by the Massachusetts Heart Association.     

心肌梗死对大鼠心肌能量代谢途径中关键酶的影响及意义

目的探讨大鼠心肌梗死后心肌组织中能量代谢变化的分子机制,为心肌梗死的治疗提供理论依据。方法结扎SD大鼠左冠状动脉前降支复制心肌梗死模型后,分别于1天、7天、1个月时处死动物,采用ELISA方法分析大鼠左心室组织中乳酸脱氢酶、脂酰辅酶A合成酶、肉碱脂酰转移酶、柠檬酸合成酶、己糖激酶的含量及乳酸脱氢酶、己糖激酶的活力。结果大鼠心肌梗死后1天,左心室组织中乳酸脱氢酶、脂酰辅酶A合成酶、肉碱脂酰转移酶、柠檬酸合成酶的浓度下降,己糖激酶的浓度增加(P<0.05)。酶的活力变化与酶的含量变化相一致。心肌梗死后1个月时这些关键酶的变化恢复至大致正常水平。结论心肌梗死后的急性期,左心室存活的心肌组织中有氧代谢相关的关键酶表达下调,无氧糖酵解相关的关键酶表达上调。随着病程的进展上述变化恢复,这可能是心脏重构过程中的一种代偿调节机制。     

Inhibition of sodium-dependent calcium overload to treat myocardial ischemia

Because intracellular sodium and calcium overload play a key role in both mechanical and electrical dysfunction during myocardial ischemia, inhibition of the late sodium current would be expected to decrease the intracellular sodium and calcium overloads and thereby reduce their undesirable effects. Ranolazine selectively inhibits late sodium current relative to peak sodium current, and attenuates the abnormalities of ventricular repolarization and contractility associated with ischemia. This is the currently proposed mechanism (hypothesis) of action of the effects of ranolazine during myocardial ischemia.     

慢性丙型肝炎患者能量代谢特点分析

目的：研究慢性丙型肝炎（CHC）患者能量代谢特点,为临床营养干预治疗提供依据。方法选取首都医科大学附属北京佑安医院2004年12月－2014年9月收治的70例 CHC 患者及30例健康对照（HC）者为研究对象,应用代谢车进行能量代谢指标测定,包括静息能量消耗（REE）、预测 REE（pREE）、呼吸商（RQ）,以及碳水化合物氧化率（CHO％）、脂肪氧化率（FAT％）和蛋白质氧化率（PRO％）。计数资料采用χ2检验,计量资料两组比较采用独立样本 t 检验,三组比较采用单因素方差分析。结果CHC组 REE、REE ／pREE（％）分别为（1360．46±467．55）kcal／d、（99．07±32．92）％,与 HC 组比较差异均无统计学意义（P 值分别为0．169、0．660）。CHC 组 RQ、CHO％分别为0．82±0．06、（35．80±19．56）％,低于 HC 组（P 值均为0．000）。CHC 组 FAT％、PRO％分别为（46．64±22．76）％、（17．56±8．80）％,高于 HC 组（P 值分别为0．011、0．000）。CHC 轻度、中度、重度组 REE ／pREE（％）分为（93．47±26．57）％、（105．42±37．88）％、（116．09±46．24）％,3组比较差异无统计学意义（P ＝0．092）;RQ 分别为0．84±0．06、0．81±0．06、0．78±0．05,3组比较差异有统计学意义（P ＝0．001）。不同基因分型肝损伤程度差异无统计学意义（P ＝0．312）,1b 基因型组 RQ 为0．81±0．06、低于非1b 基因型组0．85±0．06,差异有统计学意义（P ＝0．010）。结论CHC 患者 REE 总体呈正常代谢状态,随着肝损伤程度加重,REE 增加;CHC 患者存在营养物质代谢障碍,以 FAT％及 PRO％上升,CHO％降低为主,与肝功能损伤程度及基因分型有一定相关性。     

The effect of age on glucose and energy metabolism in brain cortex of rats

It is well documented that the mature human brain oxidizes only glucose to obtain energy under physiological, nonstarved conditions. Through adulthood to the beginning of senescence, the balance between oxygen and glucose consumption of the brain was found to be unchanged as the basis for energy production. Beyond the age of 70 yr, however, cerebral glucose consumption appears to decrease. In the present study, the effect of advancing age on glucose and energy metabolism in brain cortex of rats was investigated. The study was carried out in male Wistar rats, 6 (young adult), 12 (adult), 24 and 30 (both aged) mth of age. Male Wistar rats may be designated as being 'aged' from 24 mth of life onwards. Intermediates of glycolysis, tricarboxylic acid cycle and energy-rich compounds were measured by means of sensitive standard enzymatic methods under steady-state conditions of arterial normotension, normoxemia, normocapnia and normothermia in anesthesia with 0.5 vol% halothane and nitrous oxide/oxygen 70:30. The 12-mth-old adult rats served as controls. The glucose concentration in brain cortex was found to be about 1.5 times higher in 6-mth-old than in 12-mth-old animals but did not differ in the 12-, 24-, and 30-mth-old rats. Besides glucose, fructose-1,6-phosphate and ATP decreased from young adult to adult rats while pyruvate, malate and creatine phosphate diminish with advancing age. A tendency to reduction with aging was also evident in glucose-6-phosphate, fructose-1, 6-diphosphate, and lactate. The fall in substrate concentrations may be attributed to the reduced activity of enzymes acting in glucose breakdown. It is concluded that glucose and energy metabolism may diminish with the process of normal aging, but that the reduction is of only moderate extent.     

States of myocardial metabolism related to ischemia

Energy metabolism of the heart in ischemia is mainly characterized by oxygen deficiency and lack of lactate removal. However, under certain circumstances substrate deficiency might contribute to disturbances of energy supply as well. Capillary permeability was determined from tracer washout kinetics of isolated hearts. Regulation of mitochondrial respiration was estimated from the relationship of phosphorylation potential vs. oxygen consumption. The results obtained suggest that at least under experimental conditions substrate supply at the level of capillary exchange can be a rate-limiting figure, as well as substrate supply at the mitochondrial level, i.e., NADH supply. The latter was inferred from the effects of cobalt and strontium ions on the regulation of respiration.     

Body iron metabolism and pathophysiology of iron overload

Iron is an essential metal for the body, while excess iron accumulation causes organ dysfunction through the production of reactive oxygen species. There is a sophisticated balance of body iron metabolism of storage and transport, which is regulated by several factors including the newly identified peptide hepcidin. As there is no passive excretory mechanism of iron, iron is easily accumulated when exogenous iron is loaded by hereditary factors, repeated transfusions, and other diseased conditions. The free irons, non-transferrin-bound iron, and labile plasma iron in the circulation, and the labile iron pool within the cells, are responsible for iron toxicity. The characteristic features of advanced iron overload are failure of vital organs such as liver and heart in addition to endocrine dysfunctions. For the estimation of body iron, there are direct and indirect methods available. Serum ferritin is the most convenient and widely available modality, even though its specificity is sometimes problematic. Recently, new physical detection methods using magnetic resonance imaging and superconducting quantum interference devices have become available to estimate iron concentration in liver and myocardium. The widely used application of iron chelators with high compliance will resolve the problems of organ dysfunction by excess iron and improve patient outcomes.     

卡维地洛改善大鼠肥厚心肌能量代谢及其机制

目的探讨卡维地洛对压力超负荷大鼠肥厚心肌能量代谢的影响及其机制。方法将雄性SD大鼠随机分为假手术组、腹主动脉缩窄组和卡维地洛治疗组,15周后观察大鼠血流动力学参数、心室重构指标。采用密度梯度法提取大鼠心肌线粒体,用抑制剂终止法测定线粒体腺苷酸转运体（adenine nucleotide translocator,ANT）的转运活性,高效液相色谱法测量心肌组织及线粒体内腺苷酸含量。结果大鼠腹主动脉缩窄术后15周出现左心室肥厚及心功能减退;组织及线粒体内ATP、ADP及（ATP+ADP）含量及ANT转运活性降低。卡维地洛减轻心室肥厚、改善心功能的同时,增加组织及心肌线粒体腺苷酸含量,增强ANT转运活性。结论肥厚心肌心功能减退,心肌线粒体腺苷酸含量及ANT活性降低,使能量的产生和利用异常。卡维地洛改善心肌肥厚和心功能,且可能通过增强ANT活性而促进线粒体内产能,从而改善心肌能量代谢。     

用基因芯片研究卡托普利对糖尿病心肌病变大鼠心肌组织表达谱的影响

含4000个基因的基因芯片与荧光标记心肌mRNA杂交结果显示，卡托普利能够改善糖尿病所损害的心肌的能量供应，减轻氧化应激、炎症反应、间质纤维化和增生，还能对抗细胞凋亡，对心肌起保护作用。     

阿司匹林对脑缺血-再灌注大鼠脑能量代谢的影响

目的观察阿司匹林（ASA）对脑缺血一再灌注大鼠脑组织能量代谢的影响。方法取雄性sD大鼠50只，随机分为假手术组（12只）、溶剂组（26只）、ASA组（12只），根据再灌注时间将每组再分为24、72h两个亚组。线栓法制作大脑中动脉缺血2h，再灌24、72h模型。ASA组大鼠于再灌注同时灌胃给予ASA，60mg／kg（60mgASA加0．05ml无水乙醇助溶，用中性PBS液定容至10m1），1ml/100g。溶剂组大鼠灌胃给予等体积的0．5％无水乙醇PBS溶液。高效毛细管电泳分析法测定三磷酸腺苷酶（ATP）含量，无机磷法测定Na＋-K＋-ATP酶和Ca2＋-ATP酶活性，比色法测定乳酸脱氢酶及乳酸含量。结果①ASA组大鼠再灌注24、72hATP含量为（27．7±3．5）、（29．7±2．5）μml/g（湿重）；Na＋-K＋-ATP酶为（8．6±0．9）、（7．8±0．6）μmol·mg-1·h-1；Ca2＋-ATP酶为（6．1±0．8）、（6．6±0．7）μmol·mg-1·h-1，与溶剂组大鼠的（10．3±1．0）、（4．6±0．8）μmol／g（湿重），（4．5±0．7）、（5．8±0．8）及（4．5±0．4）、（2．5±0．5）μmol·mg-1·h-1比较，差异有统计学意义（P〈0．01或0．05）；与假手术组比较，除Ca2＋ATP酶含量高于假手术组[（4．3±0．5）、（4．6±0．3）μmol·mg-1·h-1]外，其他指标差异无统计学意义。②ASA组再灌注24、72h乳酸含量为（0．68±0．25）、（0．62±0．15）mmol／g（蛋白）；乳酸脱氢酶活性为（9769±957）、（9677±532）U／g（蛋白）；与溶剂组大鼠的（0．42±0．12）、（0．33±0．16）mmol／g（蛋白），（4033±723）、（5902±689）U／g（蛋白）比较，差异有统计学意义（P〈0．01或0．05）；与假手术组大鼠的（0．58±0．19）、（0．61±0．23）mmol／g（蛋白），（9430±273）、（9382±375）U／g（蛋白）比较，差异无统计学意义。结论阿司匹林对脑缺血-再灌损伤24和72h大鼠脑组织均有明显的保护?     

达格列净对急性心肌梗死后大鼠的心肌电活动影响的研究

目的探讨达格列净对急性心肌梗死(acute myocardial infarction,AMI)后大鼠心室结构及心室肌电活动稳定性的影响。方法将健康成年Sprague-Dawley(SD)雄性大鼠24只随机分为三组:正常对照组(NC组,8只)、安慰剂组(PB组,8只)达格列净组(DAPA组,8只)。NC组、PB组给予1 ml·kg^-1·d^-1生理盐水灌胃处理,DAPA组给予1 ml·kg^-1·d^-1达格列净灌胃处理,一天一次。给药14天后,三组大鼠经外科开胸手术,剪开心包,NC组只观察,PB组和DAPA组通过结扎前降支动脉制备AMI模型,建模成功后即行超声心动图测量左心室舒张末期内径(left ventricular end diastolic dimension,LVEDD)、左心室收缩末期内径(left ventricular end-systolic diameter,LVESD)和左心室射血分数(left ventricular ejection fraction,LVEF);通过SiS2程序性刺激评估三组大鼠左心室有效不应期(1eft ventricular effective refractory period,LVERP)、SiS连续刺激测定心室颤动阈值(ventricular fibrllation threshold,VFT);利用Masson染色检测左心室心肌纤维化程度。结果分析比较三组小鼠心动超声各指标变化情况:①LVERP:PB组、DAPA组较NC组明显缩短[PB组比NC组(9.13±1.04)ms比(17.86±2.03)ms,P<0.01;DAPA组比NC组(14.37±1.25)ms比(17.86±2.03)ms,P<0.01];然而DAPA组较PB组增加[(14.37±1.25)ms比(9.13±1.04)ms,P<0.01]。②VFT:PB、DAPA组的VFT较NC组均明显降低[PB组比NC组(2.88±1.29)V比(10.07±0.98)V,P<0.01;DAPA组比NC组(7.44±1.03)V比(2.88±1.29)V,P<0.01]。③LVEDD:PB组LVEDD较NC组明显增加[(10.00±1.12)mm比(6.10±1.79)mm,P<0.05];DAPA组LVEDD较PB组明显降低[(7.98±0.97)mm比(10.00±1.12)mm,P<0.05]。④LVESD:PB组、DAPA组LVESD均较NC组增加[PB组比NC组(8.01±0.76)mm比(3.25±1.82)mm,P<0.05;DAPA组比NC组(5.94±0.82)mm比(3.25±1.82)mm,P<0.05];DAPA组LVESD较PB组明显降低[(5.94±0.82)mm比(8.01±0.76)mm,P<0.05]。⑤LVEF:PB组、DAPA组LVEF均较NC组显著下降[PB组比NC组(23.92±2.04)%比(49.75±2.07)%,P<0.05;DAPA组比NC组(35.85±2.15)%比(49.75±2.07)%,P<0.05];进一步比较发现,DAPA组较PB组增加[(35.85±2.15)%比(23.92±2.04)%,P<0.05]。⑥左心室心肌纤维化程度:PB组、DAPA组左心室心肌纤维化程度均较NC组增加[PB组比NC组(45.69±3.19)%比(30.07±2.19)%,P<0.05;DAPA组比NC组(35.13±2.17)%比(30.07±2.19)%,P<0.05];进一步比较发现,DAPA组较PB组明显减小[(35.13±2.17)%比(45.69±3.19)%,P<0.05]。结论达格列净可以增加AMI大鼠左心室的电活动稳定性,降低左心室纤维化,改善心室重塑。     

Alterations in cardiac oxygen consumption under chronic pressure overload

Summary Hypertension and resulting left ventricular hypertrophy was induced in young male Wistar rats (60 to 70 days old) by narrowing of one renal artery (Goldblatt II). 8 and 24 weeks after operation, myocrdial oxygen consumption was measured on a modified in situ heart-lung preparation with nearly isovolumetric left ventricular contractions. Measured myocardial oxygen consumption was related to left ventricular wall stress. The myosin isoenzyme pattern of each heart was determined with pyrophosphate gel electrophoresis.Oxygen consumption related to wall stress averaged over the entire heart cycle amounted to 15 moles O₂/g·min 8 weeks after operation, and 24.4 moles O₂/g·min in age-matched controls ( 38%, p<0.0005). When wall stress was averaged over systole, oxygen consumption of the hypertrophied hearts amounted to 0.112 moles O₂/g·beat, and 0.149 moles O₂/g·beat in the controls ( 25%, p<0.05). The proportion of VM-3 (the cardiac myosin isoenzyme of lowest ATPase activity) increased from 26.3% in the controls to 30.1% in the Goldblatt hearts ( 14%, n.s.).24 weeks after operation, oxygen consumption related to wall stress averaged over the entire heart cycle amounted to 16.1 moles O₂/g·min, in age-matched controls 20.5 moles O₂/g·min ( 21%, p<0.05). When wall stress was averaged over systole, oxygen consumption of the Goldblatt hearts amounted to 0.080 moles O₂/g·beat, and in the controls 0.107 moles O₂/g·beat ( 25%, p<0.005). The proportion of VM-3 increased from 33.5% in the controls to 43.2% in the hypertrophied hearts ( 29%, p<0.05).The present findings indicate that the reduced oxygen consumption of the pressure-loaded heart should be attributed to a redistribution of myosin isoenzymes. The transformation of myocardium into a slower, but more efficiently working muscle due to an increase in VM-3 can be interpreted as an adaptational process.Supported by the Deutsche Forschungsgemeinschaft     

Effect of altered iron metabolism on markers of haem biosynthesis and intestinal iron absorption in mice

In this study, well-characterised animal models of altered iron metabolism were used to investigate link(s) between haem biosynthesis and intestinal iron absorption. Mice rendered iron deficient by feeding a low-iron diet for 3–4 weeks showed low levels of hepatic non-haem iron and hepcidin mRNA, with reduced urinary 5-aminolaevulinic acid (ALA) excretion and enhanced intestinal iron absorption. Hepatic ALA synthase activity was reduced while ALA dehydratase activity was increased. Iron-loaded mice had markedly increased liver non-haem iron and hepcidin mRNA, with increased urinary ALA excretion. Intestinal iron absorption was decreased mainly due to a reduction in transfer of absorbed iron from mucosa to the carcass. Hepatic ALA synthase activity was increased and ALA dehydratase activity moderately reduced. Mice exposed to hypoxia (0.5 atm) for 1–3 days had reduced hepatic hepcidin mRNA and urinary ALA excretion, while intestinal iron absorption was increased. Hepatic ALA synthase activity was reduced. The ALA dehydratase activity in liver and spleen was markedly enhanced. Injection of ALA to iron-deficient mice or hypoxic mice reduced their intestinal iron absorption to normal levels. This study further supports the hypothesis that alterations in haem biosynthesis influence duodenal iron absorption. ALA in particular appears to function as a modulator in controlling intestinal iron absorption.