拟除虫菊酯和马拉硫磷对鼠脑细胞肌醇磷酸酯代谢的影响

为探索拟除虫菊酯（Ｐｙ）和马拉硫磷（Ｍａｌ）对肌醇磷酸酯代谢的影响，采用ＨＰＬＣ、高效薄层色谱法（ＨＰＴＬＣ）并结合３Ｈ同位素示踪技术，分别测定了Ｗｉｓｔａｒ胎鼠和新生鼠脑细胞中的多磷酸肌醇磷脂（ＰＰＩ），ＰＰＩ磷脂酶Ｃ（ＰＰＩＰＬＣ）活力及肌醇磷酸酯（ＩＰｓ）的含量。结果表明，氰戊菊酯（Ｆｅｎ）和四甲菊酯（Ｔｅｔ）可使磷脂酰肌醇二磷酸（ＰＩＰ２）降低，对ＰＩＰ２ＰＬＣ呈明显的激活效应；Ｆｅｎ和Ｔｅｔ引起ＩＰｓ升高的敏感剂量（ＳＤ）分别是３×１０－５和４．５×１０－５ｍｏｌ，相对高剂量对ＩＰｓ的上调效应明显减弱。新霉素（Ｎｅｏ）不仅可降低ＩＰｓ各分子成份的含量，而且可阻止Ｆｅｎ和Ｔｅｔ对ＩＰｓ的上调效应。Ｍａｌ对ＩＰｓ没有明显影响，与Ｆｅｎ等剂量混用，亦未见明显的联合增毒或拮抗作用。     

镉对心肌细胞Ca^2＋通道的阻滞作用及硒的保护效应

目的探讨镉（Ｃｄ）对心肌细胞Ｃａ２＋通道阻滞作用的机制,比较亚硒酸钠（ＮａＳｅ）与硒代蛋氨酸（ＳｅＭｅｔ）两种硒化合物的保护效应。方法在培养的Ｗｉｓｔａｒ大鼠心肌细胞上观察Ｂ、Ｌ、Ｔ三型Ｃａ２＋通道的单通道电活动。结果Ｃｄ浓度为１０μｍｏｌ／Ｌ时,心肌细胞Ｂ、Ｌ型Ｃａ２＋通道受到明显阻滞;而对Ｔ型Ｃａ２＋通道没有影响。在加入Ｃｄ的同时,分别加入等浓度的ＮａＳｅ和ＳｅＭｅｔ,ＮａＳｅ能拮抗Ｃｄ对Ｂ、Ｌ型Ｃａ２＋通道的阻滞作用,ＳｅＭｅｔ仅能减轻Ｃｄ对Ｌ型Ｃａ２＋通道的阻滞,而且使Ｔ型Ｃａ２＋通道的关闭时间延长。结论Ｃｄ对心肌细胞Ｂ、Ｌ型Ｃａ２＋通道具有明显的阻滞作用,而对Ｔ型Ｃａ２＋通道没有影响;两种硒化合物均可影响Ｃｄ致心肌细胞膜Ｃａ２＋通道的阻滞作用,ＮａＳｅ的保护作用比ＳｅＭｅｔ更有效。     

β-胡萝卜素拮抗促癌剂抑制细胞间隙连接通讯的机理探讨

运用荧光探针标记方法和放射免疫分析方法分别研究了细胞内游离Ｃａ２＋（［Ｃａ２＋］ｉ）和ｃＡＭＰ的变化与促癌剂ＴＰＡ抑制细胞间隙连接通讯（ＧａｐＪｕｎｃ－ｔｉｏｎａｌＩｎｔｅｒｃｅｌｕｌａｒＣｏｍｍｕｎｉｃａｔｉｏｎ，ＧＪＩＣ）功能的关系，以及β－胡萝卜素对这些变化的影响。结果表明：ＴＰＡ使［Ｃａ２＋］ｉ显著升高，ｃＡＭＰ水平显著降低，与对照组均有显著差异；β－胡萝卜素对［Ｃａ２＋］ｉ和ｃＡＭＰ的作用分别表现为降低和升高趋势，并对ＴＰＡ升高［Ｃａ２＋］ｉ、降低ｃＡＭＰ有一定的拮抗作用。提示：ＴＰＡ升高〔Ｃａ２＋〕ｉ、降低ｃＡＭＰ，影响间隙连接通道蛋白质磷酸化，这可能是其抑制细胞ＧＪＩＣ功能的重要原因之一，而β－胡萝卜素对［Ｃａ２＋］ｉ和ｃＡＭＰ的影响可能是其拮抗促癌剂抑制ＧＪＩＣ的部分作用机制。     

中医药防治硫酸镍对大鼠肾脏Na^＋—K^＋—ATP酶,Ca^2＋—ATP酶活性 …

目的 检测肾小管细胞膜Ａａ＾＋－Ｋ＾＋－ＡＴＰ酶、Ｃａ＾２＋－ＡＴＰ酶活性,探讨扶正解毒汤（ＦＪＤ）对ＮｉＳＯ４致肾脏损伤的防治作用及其机理。方法 ＮｉＳＯ４腹腔注射染毒,ＦＪＤ灌胃防治,测定肾小管细胞膜Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶及Ｃａ＾２＋－ＡＴＰ酶活性进行评价。结果 ＮｉＳＯ４组与ＮＳ组比较,两种酶活性均明显抑制（Ｐ〈０．０１）。用ＦＪＤ防治后,两种酶活性明显改善（Ｐ〈０．０１）。结论 ＦＪＤ     

丙烯腈对大鼠肝脏Ca~(2+)-ATP酶、磷酸化酶A活力的影响

本文通过丙烯腈对大鼠肝脏Ｃａ２＋－ＡＴＰａｓｅ和磷酸化酶Ａ活性影响的研究,探讨了丙烯腈对动物肝脏钙稳态的影响,进一步阐明丙烯腈的毒作用机制。采用成年雄性ＳＤ大鼠,每天经口染毒,染毒剂量为０、１０、３０和５０ｍｇ／ｋｇ,连续染毒４２天,于染毒第１４天、２８天和４２天时分别测定各组肝匀浆Ｃａ２＋－ＡＴＰａｓｅ和磷酸化酶Ａ的活性。结果显示,丙烯腈可明显地抑制肝脏Ｃａ２＋－ＡＴＰａｓｅ（Ｐ＜０．０１）,同时可显著地激活磷酸化酶Ａ的活性,特别是高剂量组（５０ｍｇ／ｋｇ）和染毒４２天时影响最明显,相关关系分析表明,丙烯腈对Ｃａ２＋－ＡＴＰａｓｅ和磷酸化酶Ａ的活性的影响均存在较好的剂量－反应和时间－反应关系（Ｐ＜０．０１）。结果认为丙烯腈能显著地抑制大鼠肝脏Ｃａ２＋－ＡＴＰａｓｅ和激活磷酸化酶Ａ的活性,可导致大鼠肝脏钙稳态的失调。     

氟对大鼠红细胞膜Na~＋－K~＋－ATPase、Ca~（2＋）－ATPase活性的影响及“抗氟灵”的拮抗作用研究

选择健康雄性Ｗｉｓｔａｒ大鼠４０只,随机分为５组,观察氟对大鼠红细胞膜Ｎａ＋－Ｋ＋－ＡＴＰａｓｅ、Ｃａ２＋－ＡＴＰａｓｅ活性的影响及“抗氟灵”的拮抗作用。染毒及给药方式为自由饮式,染毒剂量为１８０ｍｇＦ－／Ｌ“抗氟灵浓度为２４ｇ％;染毒时间为２个月,“抗氟灵”治疗时间为１个半月。结果显示,染氟组动物红细胞膜Ｎａ＋－Ｋ＋－ＡＴＰａｓｅ、Ｃａ２＋－ＡＴＰａｓｅ活性均有显著升高,给予氟＋“抗氟灵”组比染氟组显著降低;氟中毒后给予“抗氟灵”治疗组明显低于治疗对照组。提示氟对红细胞膜Ｎａ＋－Ｋ＋－ＡＴＰａｓｅ、Ｃａ２＋－ＡＴＰａｓｅ活性有促进作用,而“抗氟灵”具有拮抗氟的作用     

氟化钠对大鼠脑突触体膜Ca~（2＋）Mg~（2＋）－ATP酶活性的影响

用体内和体外试验的方法观察ＮａＦ对大鼠脑突触体膜Ｃａ￣（２＋）Ｍｇ￣（２＋）－ＡＴＰ酶活性的影响。ＮａＦ（０．３、１．６、８．０、２０．０、４０．０ｍｍｏｌ／Ｌ）明显抑制该酶活性，抑制串分别为６．６％、１８．０％、４１．０％、５５．５％和６３．１％，半数抑制浓度为１４．８ｍｍｏｌ／Ｌ，存在明确的剂量效应与时间效应关系。酶底物动力学分析表明，ＮａＦ的这种效应属非况争性抑制。在妊娠期和哺乳期饮用５、１５和５０ｍｇ／Ｌ加氟水５０天后，母鼠脑突触体膜Ｃａ￣（２＋）Ｍｇ￣（２＋）－ＡＴＰ酶活性有降低趋势，其子鼠在１５和５０ｍｇ／Ｌ组该酶活性抑制达１１．３％和３２．１％。     

丁烯酸内酯对心肌细胞跨膜电位的影响及硒的保护作用

丁烯酸内酯对培养的Ｗｉｓｔａｒ大鼠乳鼠心肌细胞动作电位呈双相性效应，即在１００ｍｇ·Ｌ－１以下时使动作电位幅值、超射、阈电位、最大舒张电位、最大除极速率以及复极化时程一致增大；在２００ｍｇ·Ｌ－１以上时使这些参数减小。提示丁烯酸内酯在低剂量时能激活Ｃａ２＋通道，而在高剂量时能抑制Ｃａ２＋通道。含硒０５ｍｇ·Ｌ－１的亚硒酸钠和硒代蛋氨酸能减轻丁烯酸内酯（５００ｍｇ·Ｌ－１）对心肌细胞动作电位的抑制作用。     

胃腺癌组织中Fas、Bcl-2蛋白表达及其与浸润转移关系的研究

目的：为了解Ｆａｓ、Ｂｃｌ－２蛋白在胃腺癌中的表达及其意义。方法：用免疫组化ＡＢＣ法检测４８例胃腺癌中Ｆａｓ、Ｂｃｌ－２蛋白的表达。结果：中、高分化癌中Ｆａｓ蛋白阳性表达率（７０．６％、７１．４％）显著高于低分化癌（１２．５％）,（Ｐ＜０．０５）,无淋巴结转移组的胃癌Ｆａｓ阳性表达率（５５．６％）高于有淋巴结转移组（２３．８％）,（Ｐ＜０．０５）,浸及粘膜及粘膜下的胃癌Ｆａｓ阳性表达率（７１．４％）高于浸及浆膜及周围组织者（２３．５％）,（Ｐ＜０．０５）。高分化癌中Ｂｃｌ－２的阳性表达率（４２．８％）显著低于低分化癌（８７．５％）,（Ｐ＜０．０５）,Ｂｃｌ－２阳性表达与浸润深度及淋巴结转移无关。结论：Ｆａｓ表达与胃腺癌的分化、浸润转移有关,Ｂｃｌ－２表达仅与胃腺癌分化有关     

微山湖鱼虾蟹鳖螺元素含量调查

微山湖鱼虾蟹鳖螺元素含量调查马龙江，孙艺，苏政，史可江，刘钧山东省济宁市卫生防疫站（济宁２７２１４５）ＡｂｓｔｒａｃｔＴｈｅｃｏｎｔｅｎｔｏｆ１４ｍｉｃｒｏｌｅｍｅｎｔｓ（Ｋ，Ｎａ，Ｃａ，Ｍｇ，Ｆｅ，Ｍｎ，Ｚｎ，Ｃｕ，Ｃｒ，Ｍｏ，Ｐ，Ｓｅ，Ｆ，Ｃｏ）...     

氰戊菊酯和辛硫磷对大鼠背根节细胞钠通道的影响

目的　观察氰戊菊酯、辛硫磷农药单用和混用对成年大鼠背根神经节 (DRG)神经元钠通道的毒性作用。方法　应用膜片钳技术研究氰戊菊酯和辛硫磷对DRG河豚毒素敏感 (TTX S)和不敏感 (TTX R)型钠通道的作用。结果　氰戊菊酯明显延迟去极化时TTX R型钠通道的关闭时间 ,氰戊菊酯 10、5 0、10 0 μmol/L组和对照组钠通道峰电流失活时间常数分别为 (8 10± 2 41)ms、(11 78±2 76 )ms、(8 76± 1 94)ms和 (6 41± 1 32 )ms。氰戊菊酯还具有延长TTX R型钠通道尾电流的关闭时间 ,氰戊菊酯 10、5 0、10 0 μmol/L组和对照组尾电流失活时间常数分别为 (6 11± 0 5 2 )ms、(7 82±0 82 )ms、(7 2 3± 1 0 9)ms和 (4 91± 0 97)ms。氰戊菊酯对TTX S型钠通道的作用小于TTX R型 ,仅表现为对尾电流的关闭有延迟作用。辛硫磷对这两种亚型钠通道无明显影响 ,将氰戊菊酯和辛硫磷混配使用后 ,仅见氰戊菊酯作用的表现 ,未见氰戊菊酯和辛硫磷的联合作用。结论　氰戊菊酯影响DRG钠通道峰电流和尾电流 ,对TTX R型钠通道的作用大于TTX S型 ,未见氰戊菊酯和辛硫磷混配对钠通道的联合作用     

bFGF对慢性酒精中毒大鼠脑和肝组织ATP酶活力的影响

[目的]观察碱性成纤维细胞生长因子(bFGF)对慢性酒精中毒大鼠脑组织及肝组织Na+-K+-ATP酶活力和Ca2+-Mg2+-ATP酶活力,探讨bFGF对慢性酒精中毒所致的脑损伤、肝损伤的保护作用。[方法]选择成年Wistar雄性大鼠,采用白酒灌胃建立慢性酒精中毒模型,慢性酒精中毒模型建立成功的大鼠随机抽签法分为酒精中毒对照组、生理盐水(NS)对照组和bFGF治疗组,每组10只。另10只不灌白酒作为正常对照组。bFGF治疗组大鼠白酒灌胃的同时,1 h后按12μg/kg剂量肌肉注射,共14 d。各组大鼠到相对应的时间点取出各组大鼠脑组织、肝组织制成匀浆,测定脑组织、肝组织匀浆中Na+-K+-ATP酶活力和Ca2+-Mg2+-ATP酶活力。[结果]与正常对照组相比,慢性酒精中毒后大鼠脑组织及肝组织中Na+-K+-ATP酶活力和Ca2+-Mg2+-ATP酶活力均明显降低(P﹤0.01);经bFGF治疗后脑组织及肝组织中Na+-K+-ATP酶活力和Ca2+-Mg2+-ATP酶活力均明显高于酒精中毒对照组及NS对照组(P﹤0.05)。[结论bFGF能提高慢性酒精中毒脑组织和肝组织中Na+-K+-ATP酶活力及Ca2+-Mg2+-ATP酶活力,提示bFGF对慢性酒精中毒所致的脑损伤和和肝损伤具有保护作用。     

双酚A对大鼠背根神经节神经元钙离子通道电流影响

目的探讨双酚A对大鼠背根神经节(DRG)神经元钙离子通道影响。方法 SD大鼠,周龄4～6周,采用酶消化法急性分离大鼠背根神经节神经元,分别采用全细胞膜片钳技术和激光共聚焦技术记录钙电流和KCl激发钙瞬变的变化。结果双酚A(0.1、1、10、100μmol/L)呈浓度依赖性抑制大鼠背根神经节神经元钙电流,对钙通道的半数最大抑制浓度(IC50)为11.41μmol/L;10μmol/L双酚A显著改变Ca2+通道的激活特性,电流激活曲线去极化方向移动(P<0.05),该浓度双酚A同样可以抑制50 mmol/L KCL激发瞬时胞内钙浓度增加。结论双酚A对大鼠背根神经节神经元钙离子通道具有抑制作用。     

Cardiovascular effects of selective serotonin reuptake inhibitor antidepressants

This paper reviews the cardiovascular effects of fluoxetine and other selective serotonin reuptake inhibitors comparing with those of tricyclic antidepressants. The authors survey the electrophysiological mechanisms and the recent data referring on drug's actions on different ionic currents/channels. The paper primarily focuses on preclinical data, showing various effects of fluoxetine and citalopram on cardiac and smooth muscle preparations and on cardiac ionic currents. At concentrations of 0.5-50 microM, fluoxetine and citalopram exhibit depressant effects on Ca(2+)- and Na(+)-dependent electrophysiological parameters of different cardiac preparations and on cardiac Ca2+ current. At concentrations of 0.1-10 microM, fluoxetine and citalopram elicit relaxation of both vascular and intestinal smooth muscles. These results provide evidence for inhibition of cardiac Na+, Ca2+ and more recently K+ channels by fluoxetine and citalopram at concentrations close to therapeutic level. The inhibition of cardiac Ca2+, Na+ and K+ and vascular Ca2+ channels by fluoxetine and citalopram may explain most cardiovascular side effects observed occasionally with the drugs during the chronic treatment. The inhibitory effects on cardiac Ca2+, Na+ and K+ channels of fluoxetine and citalopram may result in antiarrhythmic/proarrhythmic actions. Thus fluoxetine, citalopram and other selective serotonin reuptake inhibitors similarly to tricyclic antidepressants, may exhibit cardiovascular depressant effects. The paper summarizes drug interactions that may lead risk of arrhythmia and vascular side effects. Taking all these into consideration, in depressed patients having also cardiac or liver disorders, these antidepressants should be also more rigorously applied.     

Effect of norepinephrine on inhibition of mouse brain (Na+ + K+)-stimulated, (Mg++)-dependent, and (Ca++)-dependent ATPase activities by ethanol

Norepinephrine (0.1 mM) has been reported to "sensitize" (Na+ + K+)-ATPase activity of rat brain homogenates to inhibition by ethanol. The present study extends these investigations to the mouse and includes other ATPase activities. We measured the effects of norepinephrine on the sensitivity of ethanol-induced inhibition of (Na+ + K+)-stimulated (E.C. 3.6.1.3), (Mg++)-dependent (E.C. 3.6.1.4) and (Ca++)-dependent ATPase activities. Whole forebrains from C57BL/6J mice were homogenized and assayed in vitro for ATPase activity using standard conditions. Ethanol (0.125-2.0 M) caused a dose-dependent inhibition of all three ATPases. Norepinephrine (0.1 mM) had no appreciable effect on ethanol's inhibition of (Na+ + K+)-stimulated or (Ca++)-dependent ATPase activities, but slightly antagonized ethanol's effect on (Mg++)-ATPase. These results suggest that norepinephrine has little effect on the sensitivities of specific ATPases to ethanol inhibition in mouse brain.     

氰戊菊酯对卵巢细胞、组织钙稳态和激素水平的影响

目的　观察氰戊菊酯对卵巢颗粒细胞钙稳态、卵巢组织钙稳态相关酶及血清类固醇激素水平的影响。方法　用激光共聚焦显微镜、放射免疫法和定磷比色法、酶免疫法等技术测定氰戊菊酯对人卵巢颗粒黄体细胞钙稳态和 30d染毒大鼠卵巢组织Ca2 ATP酶、磷酸化酶a(P a)活性、钙调素含量和血清雌二醇、孕酮水平。结果　氰戊菊酯浓度为 2 0 0和 2 0 μmol/L时 ,可见人卵巢颗粒黄体细胞内游离Ca2 浓度缓慢上升 ,外钙内流为胞内钙升高的主要来源。染毒大鼠Ca2 ATP酶活性总体趋势下降 ,对照组为 (10 3 9± 10 5 7) μmol磷·g蛋白 -1·h-1,1/ 2 5 0LD50 为 (80 6± 5 11) μmol磷·g蛋白 -1·h-1;P a活性增高 ,均显著高于对照组 ;钙调素含量升高 ,动情期显著升高 ,对照组为 (35 7± 2 32 ) μg/L ,1/ 2 5 0LD50 为 (90 5± 30 8) μg/L ,1/ 15LD50 为 (110 6± 36 7) μg/L ;血清雌二醇水平上升 ,对照组为 (0 2 6± 0 13)nmol/L ,1/ 2 5 0LD50 为 (0 4 1± 0 19)nmol/L ;孕酮水平下降 ,对照组为 (7 0 5± 5 6 7)nmol/L ,1/ 15LD50 为 (3 35± 1 14 )nmol/L。结论　氰戊菊酯干扰卵巢颗粒细胞内钙稳态 ,影响体内激素水平 ,钙信号通路可能为其影响机制之一。     

Effects of lead on kinetics of 3H-dopamine uptake by rat brain synaptosomes

The effects of lead on 3H-dopamine (3H-DA) uptake in rat brain synaptosomes were studied. Pb inhibited 3H-DA uptake in vitro and in vivo in a concentration-dependent manner. Altered pH versus 3H-DA uptake demonstrated comparable inhibition in buffered acidic, neutral, and alkaline pH ranges, and higher inhibition was observed in neutral pH. Kinetic studies of ATP activation of 3H-DA uptake indicated competitive inhibition by Pb. The inhibition of 3H-DA uptake followed the Na+ concentrations. The results indicate that the Pb inhibition of 3H-DA uptake is pH, ATP, and Na+ dependent.     

镉对大鼠肾皮质钙泵和钠泵活性的影响

给大鼠皮下注射不同剂量的镉金属硫蛋白（ＣｄＭＴ）后１２ｈ,染镉组大鼠尿镉、尿钙和尿蛋白含量高于对照组,且与给予的镉剂量间呈正相关;肾皮质钙泵和钠泵的活性随染镉剂量增大则逐渐降低,两者呈负相关。体外试验中,镉能抑制钙泵活性,这种抑制作用能被谷胱甘肽（ＧＳＨ）和Ｌ半胱氨酸所消除。结果表明,镉对钙泵和钠泵的抑制作用是其引起钙尿症的机理之一,ＧＳＨ和Ｌ半胱氨酸对镉抑制肾皮质钙泵活性的作用有一定的保护作用     

Ca(2+)-dependent suppression of inwardly rectified K+ channels in rat basophilic leukemia cells

A patch clamp technique was used in rat basophilic leukemia (RBL) cells to reveal the response properties of K+ Channels at different membrane potentials and the effects of Ca2+ on channel activity. In the whole-cell, cell-attached and inside-out clamp configurations, inward K+ currents markedly increased with increasing hyperpolarization, showing the inwardly rectifying property of the currents. Mean amplitude of inward K+ currents was smaller with larger (1-10 microM) internal Ca2+ than with low (less than or equal to 100 nM) internal Ca2+, indicating that high concentrations of internal Ca2+ suppress channel activity. Single channel currents and the conductance of channels were not changed by high internal Ca2+ concentrations, but the open probability of the channels was decreased in these conditions. The results suggest that, by changing K+ channel activity, Ca2+ is a factor in the regulation of inwardly rectified K+ currents in RBL cells.     

Acute inhibition of corticostriatal synaptic transmission in the rat dorsal striatum by ethanol.

The purpose of this study was to examine the effects of ethanol on synaptic transmission in the dorsal striatum in rat brain slices. The effects of ethanol on corticostriatal synaptic transmission were tested by whole-cell voltage-clamp recording. Ethanol significantly decreased corticostriatal excitatory postsynaptic currents (EPSCs) in a dose-dependent manner (10-200 mM). However, the paired-pulse ratio was not affected by the ethanol (100 mM) treatment. The amplitude of miniature EPSCs (mEPSCs) from these neurons, recorded without cortical stimulation, was decreased, but the frequency of the mEPSCs remained unchanged. Ethanol also decreased currents induced by the local pressure injection of glutamate into dorsal striatal neurons. These results suggest that ethanol inhibits glutamatergic synaptic transmission in the dorsal striatum, possibly through a postsynaptic mechanism.