克山病病区粮饲鸡雏胰腺损伤及其对维生素E需要量的研究

用克山病病区粮喂饲鸡雏三周,其胰腺外分泌腺泡出现以空泡变性为主的改变,并引起维生素 E 吸收障碍;预防病区粮喂饲鸡雏之胰腺损伤,补充维生素 E 的最低量应为500mg/kgDL—α—生育酚醋酸盐。     

克山病红细胞膜中维生素E的分析

本文对饲克山病病区糖大鼠的克山病患者红细胞膜中维生素Ｅ（ＶＥ）进行了研究，结果表明：饲克山病病区粮大鼠红细胞膜中α－ＶＥ显著低于非病区粮组；病区粮补充α－ＶＥ后，大鼠红细胞膜中α－ＶＥ显著增加，α＋ｒ－ＶＥ也有所增加，ｒ－ＶＥ则下降；病区粮补硒后，α－ＶＥ，ｒ－ＶＥ均上升；克山病患者红细胞膜中α－ＶＥ、ｒ－ＶＥ均低于病区对照和非病区对照，而病区对照和非病区对照之间无显著性差异。     

内、外环境硒营养水平与克山病发病关系的研究

目的 探讨克山病病区内、外环境硒水平以及与克山病发病的关系。方法 分别采集病区、非病区水，以及居民食用粮和病区、非病区人群头发、血清及尿样，用荧光法测定样品硒含量；并观察全省40年克山病病情动态变化，观察硒水平与克山病发病的关系。结果 克山病病区水硒、土壤硒含量低于非病区；居民食用粮（小麦、玉米、瓜干）硒含量显著低于非病区（P〈0．01）；克山病病区水、土中硒含量与当地粮食中硒含量成正相关关系。克山病患者发硒、血清硒、尿硒含量均显著低于病区健康人和非病区健康人（P〈0．01），病区健康人的血清硒、尿硒水平低于非病区健康人，发硒也有降低趋势。从1976～2004年克山病病区居民食用小麦、玉米硒含量逐渐增高，克山病患者头发、血清及尿液硒含量逐渐增高，克山病患病率逐渐降低。结论 克山病发生于低硒地区，病区居民机体硒营养水平与克山病患病率之间呈一定的负相关关系。缺硒可能是克山病发生的地区性条件致病因素。     

克山病病区粮中致病因素对肝脏损伤作用的研究

本文观察了饲克山病病区粮大鼠肝脏五种酶活性和脂质过氧化物(MDA)含量的变化。结果表明,病区粮组与非病区粮组动物相比,肝脏谷胱甘肽过氧化物酶活性和T_45′-脱单碘酶活性明显下降,谷氮酰转肽酶活性和MDA含量显著增加。提示饲克山病病区粮动物伴有原发性肝脏损伤。讨论了肝脏损伤在克山病心肌坏死发生中可能起的作用。     

克山病区粮养动物心肌T_45~′—脱单碘酶活力的改变及硒和维生素E对其保护作用的研究

本文测定了饲克山病区粮大鼠心肌T_45′—脱单碘酶活性,结果表明病区粮组动物心肌脱碘酶活力明显低于非病区粮组,并在补硒或维生素E后升高。提示心肌组织脱碘酶的损伤所致心肌组织甲状腺激素代谢改变在克山病心肌病变中可能起着重要的作用。     

补充硒、钼对克山病病区粮所致大白鼠心肌细胞膜通透性改变的影响——用辣根过氧化物酶(HRP)作示踪物的研究

已有研究证实,口服亚硒酸钠能有效地预防克山病急性发病;用施钼肥的方法也可明显降低克山病病区人群发病率。但是有关硒和钼预防克山病发病的机制目前还不十分清楚。我们以前的研究证明,用克山病病区粮喂养的大白鼠心肌细胞膜通透性显著增大,表明病区粮中存在着可致心肌细胞膜损伤的因素。本研究的目的是观察克山病病区粮补充硒或钼对大白鼠心肌细胞膜通透性变化的影响,并藉以了解硒、钼与克山病发病之间的     

山东省克山病病区粮食致豚鼠心肌病变的实验研究

应用山东省克山病病区粮，模拟克山病高发年膳食组成喂养豚鼠。３个月后描记其心电图，测血Ｓｅ含量和ＧＳＨ－Ｐｘ活性，取心肌组织行病理学检查。结果实验动物血Ｓｅ，ＧＳＨ－Ｐ降低，心电图出现心肌缺血，损伤表现，心肌呈现灶状环死的形态学改变。表明克山病病区粮可使豚鼠发生心肌病变。本文就此种心肌病变的形成及与克山病的关系进行了讨论。     

克山病致病因素与心肌内甲状腺激素代谢改变及其机制和意义的探讨

用克山病病区粮饲养动物，观察心肌内甲状腺激素代谢的改变并探讨其对克山病心肌病变的意义。结果病区粮组：１．心肌Ｔ４５＇－脱单碘酶活性降低；２．心肌组织内源Ｔ３含量减少；３．心肌线粒体α－磷酸甘油脱氢酶（α－ＧＰＤ）活性下降；４．心肌内心钠素含量增加；５．心肌组织内自由基代谢紊乱。上述改变当补充Ｓｅ和／或ＶＥ后均可恢复至正常。表明：克山病病区粮饲料中的致病因素能够导致心肌甲状腺激素的代谢紊乱，并使心肌     

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。     

内皮素在克山病心肌坏死发生中的作用

用放免分析方法，对饲予克山病病区粮大鼠血浆和心肌内皮素水平进行测定。结果表明，病区粮组大鼠ＥＴ水平明显升高，并且伴有全血、心肌ＧＳＨ－Ｐｘ和红细胞，心肌Ｃｕ、Ｚｎ、ＳＯＤ活力下降，血清和心肌ＬＰＯ含量增高。结果提示；ＥＴ水平的变化可能作为一种中间环节参与克山病的发病机制；ＥＴ升高可能是使克山病的心肌坏死具有缺血缺氧特征的一个重要因素。     

Autoradiographic analysis of 125I-insulin-like growth factor II internalization into pancreatic acini

The internalization and intracellular distribution of 125I-insulin-like growth factor II (125I-IGF II) in mouse isolated pancreatic acini was studied by electron microscope autoradiography. 125I-IGF II was rapidly internalized; after 30 min over 70% of silver grains derived from the bound hormone were localized over the interior of the cells. The grain distribution from 125I-IGF II differed significantly from both a random grain distribution and that derived from bound 125I-insulin. The majority of intracellular 125I-IGF II grains were over the endoplasmic reticulum and Golgi; the Golgi showed the highest density of intracellular grains. Pretreatment of acini with 10 nM cholecystokinin octapeptide (CCK 8) reduced both the amount of acinar-associated IGF II and the density of intracellular 125I-IGF II grains. Moreover, CCK 8 altered the relative distribution of grains from 125I-IGF II between organelles. These studies indicate, therefore, that 125I-IGF II is internalized by pancreatic acini, and that this internalization is regulated by CCK 8.     

克山病病区粮喂饲大鼠组织维生素E和Se GSH—Px的测定分析

用克山病病区粮喂饲大鼠15周,其肝脏、心脏、胰腺、肾脏、脾脏及全血Se GSH-Px活性都明显低于非病区粮喂养的大鼠,骨骼肌Se GSH-Px活性亦有降低的趋势,但差异不显著。Vit.E测定的结果表明,用病区粮喂养的大鼠肝脏和血清中Vit.E的含量明显高于用非病区粮喂养的大鼠;肾脏、脾脏和胰腺中Vit.E的含量和非病区粮组大鼠相比,亦有增高的趋势,但没有统计学差异;唯独在心肌和骨骼肌中Vit.E的含量两组间基本相同,病区粮组无丝毫增多迹象。 病区粮喂养大鼠肝脏和血清中Vit.E含量明显增多是吸收增多的表现,是对体内低硒的代偿反应,说明病区粮喂养大鼠体内对Vit.E的需要量增加。Vit.E在体内变化不一致,说明各脏器对Vit.E的摄取能力存在着差异,由于心肌和骨骼肌摄入Vit.E的能力较弱,尤易发生Vit.E相对不足的现象,成为克山病病变之主要靶器官。因此应重视硒和Vit.E联合缺乏在克山病发病中的作用。     

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。     

克山病病区居民经济状况对内环境硒的影响

目的：观察克山病区居民状况对内环境硒水平的影响。方法：选择克山病病区6个发病村,连续10年观察居民的头发、小麦、玉米、瓜干的硒含量变化,调查居民经济收入及人均占有粮食。结果：病区居民发硒含量逐年升高,粮食硒含量相对恒定,经济状况不断改善,发硒和经济收入成正相关关系,和粮食硒含量无相关关系。结论：病区居民经济状况好转能使硒营养状况改善。     

Effect of obstructive jaundice on amylase secretion in rat pancreatic acini

The effect of obstructive jaundice on pancreatic amylase secretion was studied in isolated pancreatic acini prepared from bile duct ligated rats (7 days postoperatively), sham operated rats being used as control. Obstructive jaundice caused increase in pancreatic wet weight, pancreatic protein content and pancreatic amylase content by 27.9%, 40.1% and 33.2%, respectively. In acini prepared from obstructive jaundice group, compared with acini from sham operation group, responsiveness to cholecystokinin (CCK) and carbachol was decreased when amylase release was expressed as the percentage of total amylase activity initially present in acini. However, sensitivity to both secretagogues was unchanged when expressed as the percentage of maximally stimulated amylase release. The dose-response curves to Ca2+ ionophore for amylase release were similarly shaped in both groups. These results suggested that a pancreatico-trophic effect, compared with altered responsiveness of pancreatic acini, should play a major role in hypersecretion in obstructive jaundice.     

Toxic effects of oxygen-derived free radicals on rat pancreatic acini; an in vitro study.

Isolated pancreatic acini were incubated with either a combination of xanthine and xanthine oxidase which generates superoxide (O2), or hydrogen peroxide (H2O2), and the direct cytotoxic effect of active oxygen species on the pancreatic acini was examined in vitro in the isolated pancreatic acini system of the rat. Both amylase secretion and lactic dehydrogenase discharge were increased dose-dependently by the addition of xanthine and xanthine oxidase, and suppressed by the addition of a superoxide scavenger, superoxide dismutase. In addition, amylase and lectate dehydrogenase discharge was increased dose-dependently by hydrogen peroxide and decreased by catalase. These results suggest that superoxide and hydrogen peroxide directly injure pancreatic acinar cells and that active oxygen species are involved in the pathogenesis of acute pancreatitis.     

Analysis of muscarinic receptors on rat pancreatic acini by using 125I-quinuclidinyl benzilate and N-[3H]-methylscopolamine

To analyze muscarinic receptors on rat pancreatic acini, we studied the binding of 125I-quinuclidinyl benzilate (125I-QNB) and N-[3H]-methylscopolamine ([3H]-NMS) to these acini. Binding of 125I-QNB and [3H]-NMS to acini was specific and reversible. 125I-QNB bound to low affinity site, which was not recognised by [3H]-NMS. However, nonspecific binding of 125I-QNB to acini was very high (46%), so 125I-QNB may be inadequate to analyze muscarinic receptor on pancreatic acini. Muscarinic receptors are classified in two groups, M1 and M2, according to affinity of pirenzepine which binds to M1 receptor selectively. Pirenzepine was 530 times less potent than atropine in inhibiting the binding of 125I-QNB, and 250 times less potent than atropine in inhibiting the binding of [3H]-NMS. These results suggest that muscarinic receptors on pancreatic acini are mainly M2 receptors.     

Effects of cholecystokinin and carbachol on membrane fluidity in pancreatic acini

The effects of pancreatic secretagogues on the membrane fluidity of pancreatic acini were investigated using 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene iodide as a probe. Two kinds of pancreatic secretagogues, one category of which induces acute pancreatitis (cholecystokinin and carbachol) and another which does not induce acute pancreatitis (bombesin, CCK-JMV-180, and secretin), as well as lecithin were used to investigate the effect of changes in membrane fluidity of acini. Our study revealed that the membrane fluidity of the pancreatic acini was unaffected by a physiological dose (10^–11 M) of cholecystokinin. However, stimulation with a supramaximal dose of cholecystokinin (10^–8 M) increased membrane fluidity markedly within 20 min. Membrane fluidity increased dose-dependently with increasing CCK stimulation. A supramaximal dose of cholecystokinin also induced bleb formation and increased LDH release. These phenomena were blocked by simultaneous incubation with CR1505 (Loxiglumide), a potent antagonist of peripheral cholecystokinin receptors. A supramaximal dose of carbachol (10^–3 M) also induced increases in the membrane fluidity. Pancreatic secretagogues that do not induce acute pancreatitis did not induce alterations in membrane fluidity. Lecithin increased both membrane fluidity and LDH release. These observations suggest that this increase in membrane fluidity of the pancreatic acini may be related to membrane alteration and to functional damage of the acini. These observation can serve as a window to detect the development of acute pancreatitis at an early stage.This study was supported by Scientific Research grant C-06671267 from the Ministry of Education, Science and Culture, and by a grant from the Ministry of Health and Welfare of Japan.     

纤维囊性病与克山病的病因学,脏器病理学的共同点

克山病(Keshan Disease、简称 KSD)与纤维囊性病(Cystic Fibrosis 简称 CF)有其共同特点,如心肌呈散在性灶性坏死和纤维变,发病年龄多为胎儿或学龄前儿童等。而肝脏和胰腺损害为纤维囊性病的特征性病变。本文作者对克山病尸检材料作了进一步研究。在已确诊的1700例克山病病例中发现595例(35%)有纤维囊性病的胰腺改变,均为胎儿和学龄前儿童。其中850例(50%)表现出不同程度的灶性胆汁性肝硬变,85例(5%)发展成严重的小叶性肝硬化。纤维囊性病和克山病的另一共同点是易感个体的硒元素缺乏,易感个体多为胎龄17周至6个月的胎儿或是早期幼儿。克山病和纤维囊性病缺硒的表现是有区别的,但在基本的细胞水平及组织水平的病理生理学上,二者即便不是完全一致,已是十分相近的。     

The inhibitory effect of cholecystokinin on phosphatidylcholine synthesis in isolated rat pancreatic acini (II)]

To better understand the mechanism underlying the inhibition induced by cholecystokinin (CCK) of phosphatidylcholine (PC) synthesis, the effects of CCK treatment on the activities of enzyme involved in PC synthesis via CDP-choline pathway were studied in isolated rat pancreatic acini. CCK treatment of acini reduced CTP: phosphocholine cytidylyltransferase activity in both cytosolic and particulate fraction. However, CCK treatment of acini did not alter the activities of choline kinase and phosphocholinetransferase in acini. When acini were labeled with [3H] myristic acid and chased, CCK8 (1 nM) reduced the synthesis of [3H] myristic acid labeled-PC to 27% of control after 60 min-chase period. This inhibition of PC synthesis induced by CCK was accompanied by a delayed disappearance of [3H] diacylglycerol (DAG), the radioactivity of which was 225% of control at 60 min. CCK also induced an increase in [3H] triacylglycerol and [3H] phosphatidic acid in acini. These results suggest that CCK inhibits PC synthesis by inducing the inhibition of CTP: phosphocholine cytidylyltransferase activity. The inhibition by CCK of PC synthesis may contribute to the sustained accumulation of DAG in pancreatic acinar cells.