氯化镉对大鼠肝线粒体和微粒体膜功能的影响

体外观察ＣｄＣｌ２对大鼠肝线粒体和微粒体膜流动性，膜结合酶活性，脂质过氧化产物丙二醛（ＭＤＡ）生成的影响以及维生素Ｃ的拮抗作用。结果表明，Ｃｄ２＋可在较短时间内引起膜流动性的降低和ＭＤＡ的增高，并伴有膜结合酶活性的抑制；维生素Ｃ处理不能改善膜流动性的降低。但能完全拮抗ＭＤＡ的增高，并部分缓解Ｃｄ２＋对葡萄糖－６－磷酸酶的抑制，提示Ｃｄ２＋膜毒性并非单纯由脂质过氧化所致，其中包括了对膜脂双层的直接作用。     

几种香茶菜属二萜化合物对自由基导致线粒体损伤的保护作用

目的了解香茶菜属二萜类化合物冬凌草甲素（Ｏｒｉｄ）、腺花香茶素（Ａｄｅ）、黄花香茶菜素（Ｓｃｕｌ）是否具有抗氧化作用。方法用分光光度法测定脂质过氧化物丙二醛（ＭＤＡ）含量及线粒体肿胀度。用荧光分光光度法测定线粒体膜流动性。结果Ｏｒｉｄ,Ａｄｅ,Ｓｃｕｌ４０,８０,１６０μｍｏｌ·Ｌ－１抑制铁－半胱氨酸（Ｆｅ２＋－Ｃｙｓ）引起的肝线粒体ＭＤＡ形成,并呈剂量依赖关系。Ｏｒｉｄ,Ａｄｅ,Ｓｃｕｌ１６０μｍｏｌ·Ｌ－１抑制肝线粒体膜流动性下降（Ｐ值分别为２．２９７±０．０２２,０．３８９±０．００９,０．３８２±０．０１３,Ｆｅ２＋－Ｃｙｓ的Ｐ值为０．４２３±０．０１４）;Ａｄｅ１６０μｍｏｌ·Ｌ－１还可抑制脂质过氧化引起的肝线粒体肿胀。结论Ｏｒｉｄ,Ａｄｅ,Ｓｃｕｌ可能通过抑制脂质过氧化而产生抗氧化作用     

氢化泼尼松的肝毒性机理研究

氢化泼尼松１０，２０ｍｇ／ｋｇ可显著增加肝脏ＭＤＡ含量，降低肝微粒体及线粒体膜荧光强度，荧光偏振度及平均微粘度同时肝我浆及微粒体ＧＳＴ酶活性亦降低，结果表明，Ｐｒｅｄ可增加直脏膜脂质过氧化作用及膜流动性，降低ＧＳＴ酶催化的肝结合功能。     

褪黑素拮抗鼠肝线粒体自由基产生的实验研究

目的观察褪黑素拮抗氧自由基和对膜脂质过氧化损伤的保护作用。方法用电子自旋共振技术，以ＤＭＰＯ和４－ＰＯＢＮ为捕集剂，捕集Ｆｅｎｔｏｎ反应产生的羟自由基和Ｆｅ２＋启动的鼠肝线粒体膜脂质过氧化产生的脂类自由基，以脂肪酸自旋标记物５－Ｄｏｘｙｌ和１６－Ｄｏｘｙｌ标记线粒体膜，研究脂质过氧化损伤后膜流动性的变化。结果褪黑素对羟自由基和脂类自由基有良好的清除作用，５０％清除浓度分别为１８６μｍｏｌ·Ｌ－１和４５０μｍｏｌ·Ｌ－１，而且在５００μｍｏｌ·Ｌ－１浓度范围内能防止脂质过氧化引起的线粒体膜流动性降低。结论褪黑素是一个有效的抗氧化剂，能防止生物膜的脂质过氧化损伤。     

维生素E对创伤小鼠T细胞功能以及脂质过氧化和膜流动性的影响

观察了创伤小鼠Ｔ细胞丙二醛（ＭＤＡ）含量、膜流动性、Ｔ细胞功能的变化以及维生素Ｅ（Ｖ－Ｅ）的治疗作用。结果显示，创伤后Ｔ细胞ＭＤＡ含量增加；Ｔ细胞质膜，线粒体膜及微粒体膜流动性降低；Ｔ淋巴细胞转化、白介素２（ＩＬ－２）的产生、ＩＬ－２受体（ＩＬ－２Ｒ）的表达以及ＩＬ－２介导的淋巴细胞增殖反应均受抑。这些变化同ＭＤＡ的改变均密切相关。Ｖ－Ｅ（５０或１００ｍｇ·ｋｇ－１·ｄ－１，ｉｍ×４ｄ）可明显逆转各指标的变化。表明创伤后脂质过氧化反应是导致Ｔ细胞膜流动性降低及Ｔ细胞功能受抑的重要原因，而Ｖ－Ｅ则具有明显的治疗效果。     

香烟依赖与血浆LPO含量及红细胞SOD活性关系的研究

检测经配对设计的５７例吸烟者和５７例健康非吸烟者的血浆过氧化脂质（Ｐ－ＬＰＯ）含量以及红细胞超氧化物歧化酶活性（Ｅ－ＳＯＤＡ）的结果表明，与健康非吸烟组比较．吸烟组的Ｐ－ＬＰＯ平均含量显著升高（Ｐ＜０．００１）、Ｅ—ＳＯＤＡ平均值显著降低（Ｐ＜０．００１），吸烟者的Ｐ－ＬＰＯ含量随吸烟者吸烟史和吸烟量的增加而升高、Ｅ－ＳＯＤＡ值随吸烟者吸烟史和吸烟量的增加而降低，并均呈线性相关（Ｐ＜０．００１）；提示吸烟者体内的氧自由基反应及脂质过氧化反应明显加剧。     

银杏叶制剂对心绞痛患者的抗氧化和抗脂质过氧化作用

目的：探讨银杏叶制剂对心绞痛患者的抗氧化和抗脂质过氧化作用。方法：检测了７８例心绞痛患者经银杏叶制剂“天宝宁”治疗前后的血浆维生素Ｃ（Ｐ－ＶＣ）、维生素Ｅ（Ｐ－ＶＥ）、β－胡萝卜素（Ｐ－β－ＣＡＲ）、过氧化脂质（Ｐ－ＬＰＯ）以及红细胞超氧化物歧化酶（Ｅ－ＳＯＤ）、过氧化氢酶（Ｅ－ＣＡＴ）、谷胱甘肽过氧化物酶（Ｅ－ＧＳＨ－ＰＸ）、过氧化脂质（Ｅ－ＬＰＯ）值。结果：与治疗前比较,治疗后的Ｐ－ＶＣ、Ｐ－     

叶下珠对肝细胞损伤的保护作用

实验证实叶下珠能明显降低ＣＣｌ_４引起的小鼠血清丙氨酸转氨酶（ＡＬＴ）的升高；抑制肝脏脂质过氧化产物丙二醛（ＭＤＡ）的生成。叶下珠体外与大鼠肝细胞共同孵育，能抑制ＣＣｌ_４所致的肝细胞膜流动性降低，降低肝细胞内钙离子浓度。结果提示，叶下珠的保护肝脏损伤作用可能与其抗脂质过氧化和膜保护作用有关。     

三尖杉酯碱对大鼠心肌肌质网膜脂过氧化及膜脂分子运动的影响

目的：研究三尖杉酯碱（Ｈａｒ）对膜脂过氧化及膜脂运动的影响．方法：膜脂过氧化用硫代巴比妥酸法测定，其含量用ＭＡＡ表示；用纳秒荧光偏振技术研究膜脂过氧化对膜脂分子运动的影响．结果：Ｈａｒ１０ｍｇ·Ｌ－１可使ＭＡＡ由１７±０８增加至５４±５１μｍｏｌ／ｇ蛋白质；随过氧化脂质含量的增加，膜脂双层的微粘度增加，磷脂分子摆动角减小（ｒ＝－０８５６５，Ｐ＜００１），Ｃａ２＋转运ＡＴＰ酶活性降低（ｒ＝－０８７１４，Ｐ＜００１）；ＤＰＨ的荧光强度减弱，荧光寿命缩短．结论：Ｈａｒ引起肌浆网膜脂过氧化，因而影响膜脂双层的运动和膜蛋白的功能．     

无机氟对大鼠生物膜脂质流动性的影响

以ＡＮＳ，ＤＰＨ为荧光探剂，用荧光偏振技术观察氟对生物膜流动性的影响。体外实验，终浓度１～１２８ｍｍｏｌ／ＬＮａＦ对大鼠脑突触体上ＤＰＨ的荧光偏振度（Ｐ值）无明显影响（Ｐ＞０．０５）；而ＡＮＳ的Ｐ值增大，即膜表层流动性降低，呈剂量－效应关系。体内以每日２０ｍｇ／ｋｇＮａＦ腹腔注射染毒５０天，观察大鼠脑突触体膜，肝细胞膜和红细胞膜的平均流动性变化，发现３种膜中ＤＰＨ的Ｐ值均显著升高（Ｐ＜０．０１）。提示氟的直接作用和通过影响体内代谢导致生物膜流动性降低。     

Effects of the calcium channel blocker verapamil and sulphydryl reducing agent dithiothreitol on atractyloside toxicity in precision-cut rat renal cortical and liver slices.

The effects of dithiothreitol (DTT), a sulfhydryl-containing agent and verapamil (VRP), a calcium channel blocker as possible cytoprotectants against the atractyloside-induced toxicity were characterized in rat kidney and liver slices in vitro using multiple markers of toxicity. Precision-cut slices (200 microM thick) were either incubated with atractyloside (2 mM) or initially preincubated with either DTT (5 mM) or VRP (100 microM) for 30 min followed by exposure to atractyloside (2 mM) for 3 h at 37 degrees C on a rocker platform rotated at approximately 3 rpm. All of the toxicity parameters were sensitive to exposure to atractyloside, but treatment with DTT or VRP alone did not provide any indication of damage to the tissues. Preincubation of slices containing either DTT or VRP for 30 min provided total protection against atractyloside-induced increase in LDH leakage in both kidney and liver slices. Increased induction of lipid peroxidation by atractyloside in liver slices was completely abolished by DTT and VRP. Both DTT and VRP provided partial protection against atractyloside-induced inhibition of gluconeogenesis in both kidney and liver slices. Atractyloside-induced ATP depletion in both kidney and liver slices was partially abolished by VRP but not DTT. The significant depletion of GSH in the kidney slices by atractyloside was completely reversed by DTT only, while VRP alone reversed the same process in liver slices. Decreased MTT reductive capacity and significant increase in ALT leakage caused by atractyloside in liver slices was partially reversed. Complete protection was achieved with both DTT and VRP against atractyloside-induced inhibition of PAH uptake in kidney slices. These findings suggest that both DTT and VRP exert cytoprotective effects in atractyloside-induced biochemical perturbation, effects that differ in liver and kidney. The effect of these agents on atractyloside has provided us with a further understanding of the molecular mechanism of its action.     

三种苯胺衍生物对大鼠外周血淋巴细胞膜损伤的比较研究

观察了三种结构类似，但致癌／致突变强度不同的苯胺衍生物如ＭＯＣＡ、ＭＤＡ和Ｄｓｐｓｏｎｅ处理雄性Ｗｉｓｔａｒ大鼠后，对其外周血淋巴细胞膜脂质过氧化作用和膜脂流动性和影响，发现有致癌作用的ＭＯＣＡ和ＭＤＡ均能诱发大鼠外周血淋巴细胞膜的脂质过氧化作用，同时还可使膜脂流动性下降。并发现ＭＯＣＡ的上述作用强于ＭＤＡ；而无致癌作用的Ｄａｐｓｏｎｅ则无上述作用。由此可以推测化学致癌物对大鼠外周血淋巴细胞膜某些     

Effects of toluene and n-hexane on rat synaptosomal membrane fluidity and integral enzyme activities.

The effects of toluene and n-hexane on rat synaptosomal membrane fluidity and the integral enzymes acetylcholinesterase (AChE) and ATPase were studied in vitro. The synaptosome membranes were isolated in Percoll and sucrose gradients. After adding toluene and n-hexane to the incubation mixture (37 degrees) in 2,4,6 and 8 mM concentrations, the fluidity changes were measured by the lateral pyrene diffusion method from Percoll-isolated membranes, and the ATPase and acetylcholinesterase activities were determined from both synaptosome isolations. Addition of toluene caused a linearly correlated increase of the synaptosomal membrane fluidity and a linear decrease of the AChE activity. The ATPase activity did not decrease linearly but dose-dependently. In contrast to the effects of toluene in vitro, addition of n-hexane in the same concentration range had no comparable influence on membrane fluidity nor on the activities of both integral enzymes despite its even higher lipid/water partition coefficient. Toluene increases synaptosomal membrane fluidity and at the same time inhibits the integral enzymes, probably by disturbing the lipid/protein interaction.     

Effects of Toluene and n-Hexane on Rat Synaptosomal Membrane Fluidity and Integral Enzyme Activities

Abstract: The effects of toluene and n-hexane on rat synaptosomal membrane fluidity and the integral enzymes acetylcholinesterase (AChE) and ATPase were studied in vitro. The synaptosome membranes were isolated in Percoll and sucrose gradients. After adding toluene and n-hexane to the incubation mixture (37°) in 2,4,6 and 8 mM concentrations, the fluidity changes were measured by the lateral pyrene diffusion method from Percoll-isolated membranes, and the ATPase and acetylcholinesterase activities were determined from both synaptosome isolations. Addition of toluene caused a linearly correlated increase of the synaptosomal membrane fluidity and a linear decrease of the AChE activity. The ATPase activity did not decrease linearly but dose-dependently. In contrast to the effects of toluene in vitro, addition of n-hexane in the same concentration range had no comparable influence on membrane fluidity nor on the activities of both integral enzymes despite its even higher lipid/water partition coefficient. Toluene increases synaptosomal membrane fluidity and at the same time inhibits the integral enzymes, probably by disturbing the lipid/protein interaction.     

川芎嗪对兔血小板膜流动性、电泳迁移率的影响及其与抗凝作用的关系

已有报道,川芎嗪是川芎有效成分之一,对其结构已进行了鉴定。实验证明,川芎嗪有抑制血管平滑肌痉挛、改善急性心肌缺血等作用,并能抑制血小板聚集、降低血小板活性。但对于抑制聚集的机理特别是对血小板膜的作用未见报道。因此本实验研究川芎嗪对兔血小板膜流动性、电泳迁移率的影响及其与抗凝作用的关系,并初步探讨以上作用与血小板膜上生理过程的联系。     

镉与离体大鼠肾微粒体膜的相互作用

本文利用荧光探剂ANS研究了Cd~(2+)与大鼠肾微粒体膜的相互作用。结果发现,Cd~(2+)能明显增加与膜结合的ANS荧光强度和荧光偏振度。用ANS荧光滴定法研究证实Cd~(2+)能降低膜ANS复合物的表观解离常数(Kd)和增加膜上ANS的结合位点数(n)。上述结果提示,Cd~(2+)能降低大鼠肾微粒体膜流动性和膜表面负电荷密度。     

Influence of polyunsaturated fatty acid supplementation and membrane fluidity on ozone and nitrogen dioxide sensitivity of rat alveolar macrophages

The phospholipid polyunsaturated fatty acid (PUFA) content and the membrane fluidity of rat alveolar macrophages were modified dose-dependently and in different ways. This was done to study the importance of both membrane characteristics for the cellular sensitivity toward ozone and nitrogen dioxide. Cells preincubated with arachidonic acid (20:4) complexed to bovine serum albumin (BSA) demonstrated an increased in vitro sensitivity versus ozone and nitrogen dioxide. The phenomenon was only observed at the highest 20:4 concentrations tested, whereas the membrane fluidity of the 20:4-treated cells already showed a maximum increase at lower preincubation concentrations. Hence it could be concluded that the increased ozone and nitrogen dioxide sensitivity of PUFA-enriched cells is not caused by their increased membrane fluidity, resulting in an increased accessibility of sensitive cellular fatty acid moieties or amino acid residues. This conclusion receives further support from other observations. These results strongly support the involvement of lipid oxidation in the mechanism(s) of toxic action of both ozone and nitrogen dioxide in an intact cell system.     

Relationship between thallium(I)-mediated plasma membrane fluidification and cell oxidants production in Jurkat T cells

The effects of thallous cation (Tl(+)) on: (a) the production of oxidant species and (b) membrane fluidity were evaluated in human leukemia T cells (Jurkat). After 72 h of incubation in the presence of Tl(+) (5-100 microM), no significant changes in cell viability were observed, although the average cell size was decreased as evaluated by steady-state light scattering. Tl(+) (5-100 microM) caused a significant increase in the concentration of cellular oxidants as measured with the probe 5(6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate (DCDCDHF). Similarly, a higher lipid oxidation products release was observed as measured by TBARS production. Both Tl(+)-mediated DCDCDHF oxidation and TBARS production were prevented when cells were supplemented with 2mM Trolox. Tl(+) (5-100 microM) also induced a concentration-dependent increase in plasma membrane fluidity, evaluated with the probe 6-(9-anthroyloxy)stearic acid (6-AS). This effect of Tl(+) was neither associated to the externalization of phosphatidylserine, nor observed in Trolox-supplemented cells. Significant correlations were found between the increase in plasma membrane fluidity and TBARS production and DCDCDHF oxidation. Together, the present results suggest that the increase in cellular oxidants caused by Tl(+) could oxidize membrane fatty acids, resulting in an increase in membrane fluidity. These effects could underlie the pathology associated with Tl(+) toxicity.     

Transdermal iontophoresis of insulin: IV. Influence of chemical enhancers

Transdermal iontophoresis per se may not be able to achieve significant permeation of large peptides like insulin, thereby necessitating the use of combination strategies involving chemical enhancers and iontophoresis. The study investigated effect of pre-treatment with commonly used vehicles such as ethanol (EtOH), propylene glycol (PG), water and their binary combinations, dimethyl acetamide (DMA), 10% dimethyl acetamide in water, ethyl acetate (EtAc) and isopropyl myristate (IPM) on insulin iontophoresis. Solvents, which acted on the lipid bilayer, were able to produce a synergistic enhancement with iontophoresis. The binary solvent systems produced either additive or no effect, when combined with iontophoresis. FT-IR studies showed that EtOH, DMA, EtAc caused lipid extraction and the former two also caused changes in skin proteins, whereas IPM caused increase in lipid fluidity. TGA studies showed that EtOH and PG caused dehydration of skin. Skin barrier property was severely compromised with DMA, followed by EtOH and EtAc, while IPM and PG had relatively minimum skin barrier altering potential. Thus, this study demonstrates the possibility of achieving higher permeation of large peptides like insulin by combining iontophoresis with chemical enhancers that act on the intercellular lipids.     

Effect of the water-soluble fraction of petroleum on microsomal lipid metabolism of Macrobrachium borellii (Arthropoda: Crustacea)

The effect of the water-soluble fraction of crude oil (WSF) on lipid metabolism was studied at critical metabolic points, namely fatty acid activation, enzymes of triacylglycerol and phospholipid synthesis, and membrane (lipid packing) properties in the freshwater prawn Macrobrachium borellii. To determine the effect of the contaminant, adults and embryos at different stages of development were exposed to a sublethal concentration of WSF for 7 days. After exposure, microsomal palmitoyl-CoA synthetase (ACS) showed a two-fold increase in adult midgut gland. Embryo's ACS activity was also affected, the increment being correlated with the developing stage. Endoplasmic reticulum acylglycerol synthesis was also increased by WSF exposure in adults and stage 5 embryos, but not at earlier stages of development. Triacylglycerol synthesis was particularly increased (18.5%) in adult midgut gland. The microsomal membrane properties were studied by fluorescent steady-state anisotropy, using the rotational behavior of the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Microsomes from midgut gland of WSF-exposed prawn showed no differences in fluidity. Nevertheless, microsomes incubated with WSF in vitro increased their fluidity in a temperature- and WSF concentration-dependent fashion. Both, aliphatic and aromatic hydrocarbons individually tested elicited an increase in membrane fluidity at 10 mg/l, but at 4 mg/l only nC10-C16 aliphatics did. In vivo results indicate that WSF increased the activity of microsomal enzymes that are critical in lipid metabolism, though this change was not due to direct alterations in membrane fluidity, suggesting a synthesis induction, or an enzyme-regulatory mechanism. Nevertheless, hydrocarbons elicited membrane fluidity alterations in in vitro experiments at concentrations that could be found in the environment after an oil spill.