褪黑素对饲低硒粮大鼠微观结构的影响

目的观察褪黑素对克山病病区低硒粮喂养的大鼠微观结构的影响。方法将SD大鼠分为3个组，分别用克山病病区低硒饲料、低硒饲料加硒、低硒饲料加褪黑素灌胃饲养，12周时检查心肌及肝脏病理损伤情况。结果12周时低硒组大鼠光镜下见心肌局限性炎症，电镜下见心肌细胞线粒体明显损伤。加硒组与褪黑素组心肌形态学检查均未发现明显的病变。12周时低硒组大鼠光镜下肝脏病变检出率明显高于其他两组。结论褪黑素可以预防低硒引起的大鼠心肌及肝脏的微观结构损伤，其保护作用可能与抗氧化机制有关。     

硒和VE对克山病病区粮及低硒人工合成饲料喂养大鼠心肌胰岛素含量的影响

饲予低硒克山病病区粮引起大鼠心肌细胞摄取胰岛素能力明显下降；在病区粮内补充一定剂量硒或维生素Ｅ可明显增加心肌细胞对胰岛素的摄取量（Ｐ＜０．０５～０．０１）；在亚硝酸钠引起的一过性缺氧条件下，单纯补硒或维生素Ｅ对心肌细胞摄取胰岛素能力无明显影响（Ｐ＞０．０５），只有联合补硒和维生素Ｅ才表现出统计学意义（Ｐ＜０．０１）；在低硒人工半合成饲料中补硒或维生素Ｅ均可显著增加心肌细胞摄取胰岛素能力（Ｐ＜０．０１）。本研究结果提示，克山病病区粮中的致病因素可原发性损害心肌细胞摄取胰岛素功能，此改变可能是病区粮引起克山病心肌损害重要环节之一。     

低硒与心肌线粒体膜的功能与超微结构关系的研究

动物实验结果表明半合成低硒饲料不足以引起心肌线粒体超微结构与内膜氧化磷酸化功能的明显变化;喂以克山病病区粮能引起心肌线粒体超微结构与能量转换功能明显的异常,但与克山病患者心肌线粒体损伤的程度比较尚有一定距离,病区粮补 Se 能明显减轻线粒体一系列的异常,这说明了克山病的形成低 Se 只是一个重要条件,尚有其它综合因素的参与,同时也在细胞分子水平上进一步肯定了 Se 对克山病的预防作用。     

硒对饲予克山病病区粮大白鼠膜结合酶活性的影响

本文用低硒的克山病病区粮和补硒饲料分别喂养两组大白鼠,对比观察其体内三种膜结合酶活力的变化。结果表明:饲病区粮大白鼠红细胞膜乙酰胆碱酯酶、肝细胞5′-核苷酸酶和心肌线粒体肌酸激酶同工酶活力显著降低;红细胞膜5′-核苷酸酶活力无明显变化。病区粮补充硒盐后饲养动物可防止或减轻上述病变。     

克山病致病因素对大鼠心肌线粒体α－磷酸甘油脱氢酶的影响

测定了克山病病区粮喂养大鼠心肌线粒体α－磷酸甘油脱氢酶（ａ－ＧＰＤ）活性，并观察了硒和维生素Ｅ对该酶的影响。结果表明，病区粮组大鼠心肌线粒体α－ＧＰＤ活力明显低于非病区粮组和常规．食组，并在补０．１μｇ／ｇ＋８００μｇ／ｇＶＥ后，α－ＧＰＤ活性升高与病区粮组比较有显著差异、本实验结果提示：１、饲克山病病区粮大鼠心肌线粒体α－ＧＰＤ活力的降低，此时的心肌可能处于甲状腺激素功能低下状态．２、硒（０．１μｇ／ｇ）＋维生素Ｅ（８００μｇ／ｇ）的补充可以升高该酶活性，改善甲状腺激素功能不足状态。     

钙硒对模拟克山病偏食喂养大鼠生长激素分泌的影响

模拟克山病偏食饲料及在这种饲料中补充钙和硒对大鼠生长和生长激素的影响。结果表明，这种克山病偏食饲料中除低硒外低钙特别突出，所饲大鼠血清钙水平及全血ＧＳＨ－Ｐｘ活性、血清总蛋白、生长激素明显低于常规食组。在克山病偏食饲料中单纯补钙或硒可明显改善大鼠生长状态及生长激素增多。表明钙和硒在病区粮偏食喂养大鼠所致生长迟缓方面及生长激素的释放中起重要作用。补充钙同时补充硒效果更好。     

克山病区低硒粮饲养大鼠心肌α1受体的变化

将 Sprague-Dawley 大鼠随机分为三组,分别用病区低硒粮饲料、病区粮加 Na_2SeO_3饲料和本校常规饲料喂养,用以研究克山病区低硒粮饲养动物心肌α_1受体变化及补硒的影响。实验结果发现,大鼠饲养两月时,常规饲料组大鼠心肌与〔~3H〕哌唑嗪的最大结合量(Bmax)为01.90±36.97fmol/mg 蛋白;补硒组略有下降;低硒组则明显降低(P<0.05)。常规饲料组大鼠心肌α_1受体与〔~3H〕哌唑嗪结合的平衡解离常数(KD 值)为2.25±0.08nM(?)补硒组仅有下降趋势;低硒组则明显降低(P<0.05)。反映克山病区低硒粮饲养可使大鼠心肌的α_1受体数量减少,受体与配体的亲和力降低。     

蛋白质对饲克山病病区粮大鼠心肌损伤的保护作用

目的　探讨克山病病区粮对大鼠心肌的影响及蛋白质的保护作用。方法　用模拟克山病病区偏食饲料及补充蛋白质饲料喂养大鼠 4个月 ,观察总增重、食物利用率、心肌病变、全血谷胱甘肽过氧化物酶 (GSH -Px)活性的变化。结果　低硒低蛋白组大鼠的总增重、食物利用率和全血 GSH - Px活性低于常规饲料组及低硒高蛋白组 (P <0 .0 1,P <0 .0 5 ) ,心肌病变检出率高于常规饲料组及低硒高蛋白组 (P <0 .0 5 )。结论　模拟克山病病区偏食饲料影响动物的生长 ,引起心肌损伤 ,补充蛋白质对大鼠心肌具有保护作用     

硒对大鼠肝去线粒体后上清液~3H—亮氨酸掺入率的影响

本实验分别用低硒的克山病病区粮,加硒病区粮和西安粮喂养大鼠,制取大鼠肝去线粒体后上清液,进行~3H-亮氨酸掺入实验。同时还测定了肝 TBA 值、谷胱甘肽过氧化物酶活性和肝硒含量。结果表明:加硒组大鼠肝去线粒体后上清液~3H-亮氨酸掺入率无论以蛋白质或以 RNA作基准都较病区组大鼠明显增加,并和西安组相似。病区组大鼠肝谷胱甘肽过氧化物酶活性、肝硒含量较加硒组和西安组明显降低,而 TBA 值却显著升高。     

硒对大鼠心肌儿茶酚胺代谢的影响

本文采用高压液相色谱—电化学检测法,观察饲克山病病区低硒粮(低硒组)和病区补硒粮(补硒组)大鼠结扎冠状动脉后,心肌去甲肾上腺素和肾上腺素的变化。结果表明(?)1、两组动物结扎冠状动脉1h 后,缺血区心肌去甲肾上腺素和肾上腺素都明显低于非缺血区。2、低硒组非缺血区心肌去甲肾上腺素和肾上腺素显著高于补硒组。3、结扎冠脉后低硒组缺血区与非缺血区心肌去甲肾上腺素含量的差值明显大于补硒组。     

Oxidative phosphorylation and aspects of calcium metabolism in myocardia of hypercholesterolaemic swine with moderate coronary atherosclerosis.

Aspects of myocardial oxidative phosphorylation and Ca2+ metabolism were studied in a swine model in which coronary atherosclerosis was induced by a combination of denudation of the endothelium of the coronary arteries plus 7--11 months of feeding a high fat--high cholesterol diet. By microscopy, a moderate amount of coronary atherosclerosis was present at the time of sacrifice, and 2 of the 14 swine hearts had old myocardial infarcts. Myocardial mitochondria from grossly normal areas showed partial uncoupling and decreased state 3 O2 uptake with 3 of 4 substrates tested. In addition, Ca2+ stimulated mitochondrial respiration was decreased in the atherosclerotic swine. In the sarcoplasmic reticulum Ca2+ uptake under conditions of heavy loading was greater in the atherosclerotic swine than in control animals. The degree of atherosclerosis was not great enough to suggest that persistent myocardial ischaemia was present. Possibly coronary artery spasm induced an intermittent ischaemia resulting in the metabolic abnormalities observed, or the changes may have been brought about by the effects of the high fat--high cholesterol diet on subcellular membranes.     

Effects of simulated ischemia and reperfusion on the sarcoplasmic reticulum of digitonin-lysed cardiomyocytes.

ATP-dependent, inorganic phosphate-supported 45Ca2+ uptake by digitonin-lysed adult rat ventricular cardiomyocytes was used to evaluate the effects of simulated ischemia and reperfusion on the physically intact sarcoplasmic reticulum. Mitochondrial reactions were inhibited with rotenone and oligomycin. 45Ca2+ accumulation in the presence of the calcium efflux inhibitors, procaine (10 mM) and ruthenium red (30 microM), was used to characterize unidirectional uptake kinetics. A decrease in pH from 7.2 to 6.6 increased the [Ca2+] K0.5 from 0.5 to 2.0 microM and reduced the apparent Vmax by 28%. In the absence of procaine and ruthenium red, at a free [Mg2+] of 0.5 mM, maximum net uptake occurred at pCa 6.2 when pH was 7.2 and at pCa 6.0 when pH was 6.6. At lower pCa, net Ca2+ accumulation declined. Increasing free [Mg2+] from 0.5 to 1 mM at pH 6.6 or to 2.5 mM at pH 7.2 increased net 45Ca2+ accumulation in the absence of procaine and ruthenium and shifted maximum uptake to pCa 5.6 and 6.0, respectively. Increases in cytosolic free [Mg2+] thought to occur during myocardial ischemia are therefore capable of inhibiting calcium efflux from the sarcoplasmic reticulum. Reducing [ATP] from 10 to 1 mM reduced maximum net 45Ca2+ uptake by 30% both in the presence and absence of efflux inhibitors. Preincubation of intact myocytes under conditions designed to simulate ischemia and reperfusion decreased 45Ca2+ uptake greater than or equal to 50%. The data indicate that myocardial ischemia and reperfusion can alter both Ca2+ accumulation and calcium release by the sarcoplasmic reticulum.     

Der subzelluläre Kalziumstoffwechsel bei experimenteller Kaliummagel-Myokardiopathie

Mechanical Parameters of the whole, Langendorff-perfused cat heart and of isolated right ventricular papillary muscles are depressed in chronic potassium deficiency. 45Ca binding of sarcoplasmic reticulum (SR) was found to be diminished and correlated with a reduced contractility of the perfused hearts. 45Ca uptake of sarcoplasmic reticulum isolated from potassium deficient hearts was also reduced. The mitrochondrial 45Ca binding and endogenous Ca concentration were increased and there was a positive correlation between these two parameters. The data suggest that a reduced SR Ca binding plays a role in the depression of myocardial contractility in chronic potassium deficiency. Increased mitochondrial 45Ca binding in the presence of reduced 45Ca binding and uptake of sarcoplasmic reticulum suggests the possibility that mitochondria are an additional myocardial calcium pool in chronic potassium deficiency.     

硒和维生素E对克山病病区粮喂饲大鼠心肌损伤的影响

本实验在克山病病区粮食中补充硒和维生素E(VE)或单独补充硒喂饲大鼠,和单纯喂饲病区粮大鼠比较,联合补充硒和VE可明显减轻亚硝酸钠引起的大鼠心肌损伤;硒加VE组大鼠红细胞高铁血红蛋白还原酶活性明显升高,其可使亚硝酸盐氧化血红蛋白形成的高铁血红蛋白迅速还原,从而减轻机体缺氧状态;硒和VE可使大鼠心肌脂质过氧化产物丙二醛含量明显减少,减轻了病区粮喂饲大鼠心肌损伤;硒加VE使大鼠血清甲状腺激素(T_3、T_4)和心肌呼吸酶(CCO、SDH)活性维持在低水平,表明其纠正了病区粮喂养大鼠心肌能量代谢紊乱,使代偿增加的血清T_3、T_4和心肌CCO、SDH活性降低。和病区粮组大鼠比,单纯加硒组大鼠除心肌谷胱甘肽过氧化物酶活性升高外,其心肌损伤未明显减轻。 上述结果提示,联合补充硒和VE在预防克山病发病上可能会有更好效果。     

Mitochondrial dysfunction observed in situ in cardiomyocytes of rats in experimental diabetes.

OBJECTIVE: The aim was to investigate effects of experimental diabetes and insulin treatment on heart myocytes, particularly on the mitochondrial function studied in situ in isolated cardiomyocytes. METHODS: 20 male Sprague-Dawley rats (140-160 g) were made diabetic by intraperitoneal streptozotocin, 70 mg.kg-1. Ten then received daily subcutaneous injections of ultra lente insulin (starting dose of 3 units.d-1) for 7-15 d from the 20th day after streptozotocin. There was a control group of 11 rats. The rats were killed 21-35 d after the induction of diabetes, and heart myocytes were isolated by collagenase digestion. The 45[Ca]2+ uptake of mitochondria in situ in permeabilised myocytes, the transmembrane potential gradient of mitochondria, and the respiration of myocytes, as well as the cell yield and cell [45Ca]2+ uptake, were examined. RESULTS: Mitochondrial uptake of [45Ca]2+ was significantly decreased in the diabetic group compared to control at cytosolic calcium concentrations between 760 nM and 44.6 microM. The mitochondrial potential of diabetic myocytes, estimated from the distribution of [3H]triphenylmethylphosphonium+, was slightly but significantly decreased from the control value. Cell respiration, measured polarographically in the presence of pyruvate and malate or succinate as oxidisable substrates, and with or without 2,4-dinitrophenol, was decreased by diabetes. The rapidly exchangeable [45Ca]2+ content in the myocyte with intact sarcolemmal membrane ("cell Ca2+ uptake") and the yield of cells from heart tissue were also diminished in diabetic rats. These changes were returned to normal by insulin treatment of 7 d or longer. CONCLUSIONS: Insulin deficiency at early stages causes defects of mitochondrial function detectable in situ in cardiomyocytes. This suggests the possibility that such alterations are causative factors in the development of diabetic cardiomyopathy.     

膳食低钙对饲克山病区粮大鼠胰岛素分泌的影响

本实验通过对模拟克山病偏食饲料中补充一定量的钙和硒来观察Wistar大鼠胰岛素(Ins)的变化。结果表明,病区粮组血钙水平最低,仅及常规食(stock)组一半;血清硒(Se),α-VE水平低于Stock组;Ins减少;血清过氧化脂质水平明显高于Stock组;血清GSH-Px活性低,有显著差异。补钙后钙水平升高,Se、α-VE水平变化不大;Ins显著升高。补Se/VE组Se、α-VE水平明显高于EM组。联合补Se/VE和Ca组Se、α-VE水平高于单纯补Se/VE组,有显著差异,Ins升高。补Se/VE、Ca各组可使过氧化脂质水平下降,有显著差异。综合分析结果表明,补Ca各组与EM组比较差异显著,表明膳食钙量对胰岛素影响极大。     

Dietary sodium restriction exacerbates age-related changes in rat adipose tissue and liver lipogenesis

To investigate the effects of prolonged dietary sodium restriction on lipid metabolism, male rats weighing 35 to 40 g (just weaned) were fed either a low-salt (LSD) or a normal salt diet (NSD) and used in metabolic experiments after 1, 2, or 3 months of diet consumption. After 2 and 3 months on the diet, LSD rats showed increased amounts of lipid in carcass and retroperitoneal tissue. In both LSD and NSD, extending the feeding period from 2 to 3 months resulted in a marked reduction in the in vivo rates of adipose tissue fatty acid synthesis that was accompanied by increases in liver lipogenesis and in the activity of adipose tissue lipoprotein lipase (LPL). However, these increases were more marked in LSD rats. Thus, in vivo rates of liver fatty synthesis and LPL activity in LSD rats, which were already higher (by about 35% and 20%, respectively) than in controls after 2 months, attained levels 50% higher than those in NSD animals after another month on the diet. Brown adipose tissue (BAT) thermogenic capacity, estimated after 2 and 3 months by the tissue temperature response to norepinephrine (NE) injection and by guanosine diphosphate (GDP) binding to BAT mitochondria, did not change in controls, but was significantly reduced in LSD rats. This raises the possibility that a decrease in overall energy expenditure, together with an LPL-induced increased uptake of preformed fatty acids from the circulation, may account for the excessive lipid accumulation in LSD rats. Taken together, the data indicate that prolonged dietary sodium restriction exacerbates normal, age-related changes in white and BAT metabolism.     

钙,硒对膳食低钙大鼠红细胞钠／钾ATP酶及钙／镁ATP酶活性的影响

实验通过向模拟克山病偏食饲料中补充一定量的钙和硒／维生素Ｅ（Ｓｅ／ＶＥ）来观察大鼠红细胞钠／钾ＡＴＰ酶及钙／镁ＡＴＰ酶（Ｎａ－Ｋ－ＡＴＰａｓｅ,Ｃａ－Ｍｇ－ＡＴＰａｓｅ）活性的变化。探讨钙和硒对大鼠ＲＢＣ膜的变化规律。结果表明,病区粮组血钙水平最低,仅及常规食（ｓｔｏｃｋ）组一半,血清硒（Ｓｅ）,α－ＶＥ水平低于ｓｔｏｃｋ组,红细胞Ｎａ－Ｋ－ＡＴＰａｓｅ,Ｃａ－Ｍｇ－ＡＴＰａｓｅ,活性降低,血清过     

Studies of the rapid effects of parathyroid hormone and prostaglandins on 45Ca uptake into chick and rat bone in vivo

The rapid effects of parathyroid hormones and a variety of prostaglandins on net uptake of 45Ca into the skeleton have been investigated in chicks and, in a limited parallel study, in immature rats. Intravenous injection of bovine (b) parathyroid hormone(1-34) (bPTH(1-34)) or 16,16-dimethyl prostaglandin E2 (16,16-dimethyl PGE2) in a 45Ca-labelled vehicle, combined with subsequent microwave fixation of tissue isotope levels, resulted in rapid (3-15 min) net inhibition of 45Ca uptake into endochondral bone (femur) in chicks (12 days old) and rats (4 weeks old). Use of 125I-labelled albumin and [14C]mannitol indicated that these responses were not a reflection of gross changes in tissue vascular or extracellular space. In rats, bPTH(1-84) also caused significant net inhibition of 45Ca uptake into femur at 10 min. Both bPTH(1-34) and 16,16-dimethyl PGE2 produced generally smaller decreases in 45Ca uptake into chick dermal bone (calvarium) at 3-15 min. In rat calvarium, however, these agents stimulated net uptake of 45Ca at these times. When microwave fixation was omitted, inhibitory responses were reduced or disappeared, while the stimulatory response in rat calvarium was enhanced. Responses to natural prostaglandins (PGE1, PGE2, PGF2 alpha and PGI2) in chicks at 3 min were similar but less marked than those to 16,16-dimethyl PGE2; 45Ca uptake into femur and, to a lesser extent in calvarium, being inhibited. In rats, PGE1, PGE2 and PGF2 alpha showed a tendency to decrease 45Ca uptake into femur while PGE1 and PGE2 both increased 45Ca uptake into calvarium.