AMPK通过增强心肌脂肪酸氧化抑制大鼠心肌肥厚

目的： 探讨单磷酸腺苷（AMP）激活的蛋白激酶（AMPK）对心肌肥厚的影响及可能涉及的作用机制。方法： 通过对大鼠行腹主动脉缩窄术（TAC）引起压力负荷增加，造成心肌肥厚的模型。术后24 h起经皮下注射AMPK的特异性激活剂AICAR(0.5 mg·kg-1·d-1)直至术后7周。处死动物前，对大鼠进行超声心动学指标的检测和血清游离脂肪酸浓度测定；处死动物，取心脏称重后计算心脏重/体重比值，测量心肌细胞的平均直径、心肌中的游离脂肪酸含量、过氧化体增殖物激活型受体α（PPARα）和肉碱棕榈酰转移酶（CPT-I）的mRNA表达。结果： （1）心肌肥厚+AICAR组大鼠的心脏重/体重比值、心肌细胞平均直径、血清及心肌中游离脂肪酸的浓度明显低于心肌肥厚对照组；（2）心肌肥厚+AICAR组大鼠心肌PPARα及CPT-I的mRNA表达明显高于心肌肥厚对照组；(3) 心肌肥厚+AICAR组大鼠心脏超声心动学指标：左室后壁舒张末期厚度、左室舒张、收缩末期内径 (PWT, LVDD, LVSD) 低于心肌肥厚对照组，左室短轴缩短率 (FS%) 则高于心肌肥厚对照组。结论： 活化的AMPK可能通过增强心肌脂肪酸氧化从而抑制压力负荷增加引起的心肌肥厚。     

Galactolipid fatty acids in brain of pyridoxine-deficient young rats

Summary The non-hydroxy fatty acids of the galactolipid fraction of brain lipids of pyridoxine-deficient rats have been analyzed. The results suggest an impairment in the pathway for the synthesis of very long chain fatty acids in the brain of pyridoxine-deficient rats.     

Palmitic acid metabolism in the soleus muscle in vitro in hypo- and hyperthyroid rats

The aim of this study was to establish whether the rate of fatty acid (FA) incorporation and its utilization by the isolated soleus muscle is modified under conditions of thyroid hormone deficit or excess. The rate of palmitic acid (PA) uptake, oxidation and incorporation into intramuscular lipids with increasing PA concentration (0.5–1.5 mM) in the incubation medium were determined. In hypothyroid rats intramuscular triacylglycerol (TG) synthesis was increased, while the rate of PA oxidation to CO₂ and incorporation into mono- and diacylglycerols (MG/DG) and phospholipids (PL) remained unchanged. In rats with triiodothyronine (T₃) excess the rate of all processes studied was enhanced, although the percentage incorporation of PA into different classes of intramuscular lipids was fairly constant and, independently of thyroid state and FA concentration in the medium, was 56–66% for TG, 9-14% for MG/DG and 24–32% for PL. Our results thus indicate that even short-term T₃ excess accelerates the rate of FA uptake and metabolism in the oxidative soleus muscle, whereas in hypothyroid rats only intramuscular TG synthesis is affected.     

Ultrastructure of the neuroglial fatty metamorphosis (virchow) in the perinatal period

Summary The ultrastructure of neuroglial fatty metamorphosis (GFM) has been investigated in the telencephalic white matter of 12 premature and mature infants (gestational age 22–40 weeks; survival 0–96 days). GFM was found in all cases apart from a 22-week-old fetus, and involves predominantly astrocytic cells (68.8%), then glioblasts (43.5%), but only 7.4% of oligodendrocytes. GFM, therefore, seems to be independent of the myelination process and indicates the vulnerability of the immature neuroglial population in the metabolic and circulatory disorders of the perinatal period. Since GFM is found in almost all children dying within the early postnatal period, this subtle alteration reflects a special form of minimal brain damage. The relationship between GFM, astrocytic hypertrophy and periventricular leucomalacia and their role in the telencephalic leucoencephalopathy are discussed.

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Zusammenfassung Die Gliazellverfettung im unreifen Großhirn-Marklager wurde bei 12 Kindern ultrastrukturell untersucht (Gestationsalter 22–40 Wochen; Überlebenszeit 0–96 Tage). Die fettige Metamorphose der Neuroglia (Virchow) fand sich in allen Fällen, ausgenommen den 22 Wochen alten Feten, und betrifft vorwiegend junge Astrozyten (68,8%), ferner zu 43,5% unreife Vorstufen, jedoch nur zu 7.4% die (z.Z. der Geburt erst in Erscheinung tretende) Oligodendroglia. Die Fett-Metamorphose der unreifen Glia stellt einen sensiblen Indikator für metabolisch-zirkulatorische Störungen der Perinatalperiode dar und erfolgt unabhängig von dem Prozeß der Markscheidenbildung. Zusammen mit einer oft auffälligen Astroglia-Proliferation ist die intracytoplasmatische Akkumulation nicht membrangebundener Lipide Ausdruck einer temporären Differenzierungsstörung der unreifen Neuroglia. Die resultierende Reifungsdissoziation mit Unterdrückung der oligodendrozytären Zellinie führt zur retardierten Markscheidenbildung und dem Bild der telencephalen Leucoencephalopathie.

     

弓形虫分离株表膜脂肪酸的色质谱分析

本文采用有机质谱法（ＧＣ／ＭＳ）对弓形虫不同分离株，虫体表膜脂肪酸的种类和含量进行观察分析，实验结果表明弓形虫速殖子细胞膜含有６种主要脂肪酸，范围在Ｃ１４－Ｃ１８之间，分别为肉豆寇酸、棕榈油酸、软脂酸、硬脂酸、油酸和亚油酸，而油酸和软脂酸约占总脂肪酸含量的７０％（５２－８４％）。本室自畸胎儿分离获得的ＳＨ多个虫株的脂肪酸含量及组分与国际标准人源ＲＨ株相一致，而ＳＨ４，ＳＨ（１０）与ＰＰ株，ＲＴ株相似，与平行观察的人和哺乳动物细胞膜的脂肪酸在含量与组分上均有明显差异，为鉴定分离的弓形虫株提供了实验依据。     

The effect of cathartic agents on transmucosal electrical potential difference in the human rectum

Summary Active ion transport in the colon is generating a transmucosal electrical potential difference (PD) of about 40 mV. Cathartic agents inhibit electrolyte and water net-absorption or cause net-secretion which should be reflected in a change of PD.In 83 normal subjects the effect of an isotonic eletrolyte solution (control) and different cathartic agents on rectal PD was tested: Laxatives (bisacodyl, rhein), bile acids (cholic and deoxycholic acid), fatty acids (oleic and ricinoleic acid) and cardiac glycosides (meproscillarin, digitoxin, digoxin). Bisacodyl, deoxycholic acid in high concentration, meproscillarin and digitoxin significantly decreased PD, while the other substances did not.Cathartics act on different transport mechanisms which together with different absorption characteristics of the proximal and distal colon may explain the difference in effecting the PD. Rectal PD measurement provides an easy and convenient tool to document effects of cathartic agents on electrolyte transport, otherwise difficult to obtain, and is applicable for clinical use.To Prof. Dr. H.P. Wolff on the occasion of his 65th birthday     

Adult hypophosphatasia without apparent skeletal disease: “odontohypophosphatasia“ in four heterozygote members of a family

Summary Twenty members of a family with adult hypophosphatasia were examined clinically and biochemically. Severe caries causing early loss of permanent teeth was the only clinical symptom which could be attributed to hypophosphatasia. None of them had a history of defective bone mineralization, rachitic skeletal alterations, and recurrent pseudofractures or fractures. An iliac crest bone biopsy of the proposita showed a normal finding corresponding to the age of the patient.Four family members in two subsequent generations were affected, thus suggesting an autosomal dominant inheritance. Their serum and leukocyte alkaline phosphatases were reduced. The phosphoethanolamine (PEA) excretion in the urine was increased to a level which suggests a heterozygote state. The serum alkaline phosphatase activity could be ascribed to the liver isoenzyme fraction. This was shown by polyacrylamide electrophoresis, by inhibition studies with organ-specific inhibitors, heat inactivation, inhibition by antibodies, and treatment with neuraminidase.The proposita had an unexplained, diffuse fatty infiltration of the liver. Thus, not only alterations of bone but also of liver metabolism in hypophosphatasia should be considered.The variety of adult hypophosphatasia described in this paper is characterized by the lack of severe bone abnormalities, the apparently autosomal dominant inheritance, and the reduction of bone and intestinal isoenzyme in the serum. Our study suggests that hypophosphatasia is a heterogenous disorder which includes both severe and clinically mild forms.     

Fatty acid synthesis in the arrested rabbit heart during ischemia

In rabbit hearts arrested by a carnosine-buffered cardioplegic solution the incorporation of [1-¹⁴C]acetate into lipids was investigated. After 10–20 and 60 min of ischemia the radioactivities of phospholipids, mono-, di-, and triacylglycerols, acyl-CoA, acylcarnitine, and free fatty acids were determined. In the first period of ischemia mainly acylcarnitine was labelled (ca. 50%) and only 25% of [¹⁴C]-activity was found in phospholipids which showed the lowest specific activity of all lipid classes. After 60 min of ischemia the percentage of total radioactivity of acylcarnitine and phospholipids was decreased, whereas that of neutral lipids was increased to more than 50%. During the increase of total radioactivity the relative specific activity of all lipids decreased except that of triacylglycerols. Only fatty acids up to chain lengths of 16 carbon atoms were labelled. Lauric and myristic acid had high specific activities. These results indicated de novo synthesis of fatty acids accumulating in triacylglycerols during ischemia of the arrested heart.     

Effect of 3-methyl-branching on the metabolism in rat hearts of radioiodinated iodovinyl long chain fatty acids

The metabolism of two new 3-methyl-branched iodovinyl fatty acids in rat hearts was evaluated by determining the subcellular and lipid pool distribution of these radiolabeled analogues after intravenous injection. Methyl branching had been introduced into the straight chain analogue, 19-iodo-18-nonadecenoic acid (IVN), to produce the monomethyl analogue, 19-iodo-3-(R,S)-methyl-18-nonadecenoic acid (BMIVN) and the dimethyl derivative, 19-iodo-3,3-dimethyl-18-nonadecenoic acid (DMIVN) in the hope of inhibiting oxidation. Since the presence of 3-methyl branching results in delayed myocardial clearance in rats, differences were sought in the lipid and subcellular distribution of these branched analogues that might correlate with the prolonged retention and reflect differences in metabolism. Hearts of rats injected intravenously with the radiolabeled fatty acids were removed and homogenized and the homogenates partitioned between the chloroform-methanol (organic) fraction and the aqueous fraction. Comparison of the distribution of radioactivity between the organic and aqueous fractions showed that most of the DMIVN and BMIVN activity was in the organic fraction with IVN activity initially divided equally between the two fractions. Identification of the lipid components of these organic fractions showed that there was slow incorporation of DMIVN into the triglyceride and polar lipid fractions with a slow loss from the free fatty acid fraction. With the straight chain IVN analogue which shows rapid washout from rat hearts, there was loss of activity from all 3 lipid components during the 60 min. The monomethyl branched BMIVN analogue demonstrated predominant storage in the polar lipid fraction with some incorporation into triglycerides. Subcellular distribution studies of the three analogues also showed differences that correlated with the observed differences in heart retention properties. With the unbranched IVN analogue, radioactivity was found primarily in the cytoplasmic fraction 30 min after injection, whereas the branched analogues demonstrated a much higher association with the microsomal and mitochondrial fractions of the heart. In rats fed prior to injection, these differences in the subcellular distribution profiles were minimized. The lipid and subcellular distribution patterns reported here for the methyl branched analogues as compared to those of the straight chain iodovinyl fatty acid may provide some understanding as to the mechanisms of retention in rat myocardium.Research supported by the Office of Health and Environmental Research, U.S. Department of Energy, under contract DE-AC0 5-840 R21400 with Martin Marietta Energy Systems, Inc.     

蚕蛹油多烯脂肪酸对大鼠血脂及血清EPA、DHA含量的影响

目的研究蚕蛹油多烯脂肪酸对大鼠体内脂质代谢及多烯脂肪酸代谢的影响.方法用高脂膳食喂养大鼠建立高脂模型,观察蚕蛹油(富含α-亚麻酸)对大鼠血清中甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDLC)、HDL-C/TC、丙二醛(MDA)及超氧化物歧化酶(SOD)、二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)和肝脏中MDA含量的影响.结果蚕蛹油可以降低大鼠血清中TC及MDA含量,升高HDL-C/TC比值,降低肝组织中MDA含量,并增加大鼠体内EPA和DHA合成.结论蚕蛹油可增加大鼠体内EPA和DHA的生成,并具有调整血脂、抗脂质过氧化作用.