Mechanisms of artemisinin antiarrhythmic action

采用全细胞电压钳技术,以确定青蒿素对分离的豚鼠心室肌细胞和狗的浦肯野纤维钾离子电流的影响．在豚鼠心室肌细胞,青蒿素呈浓度依赖关系显著降低内向整流钾电流〔ＩＫ１,膜电位为－１００ｍＶ时,ＩＣ５０为（７．２±０．８）μｍｏｌ·Ｌ－１〕,且这种抑制作用不呈现频率依赖性．５０μｍｏｌ·Ｌ－１的青蒿素降低延迟整流钾电流（ＩＫ）：时间依赖性外向钾电流（ＩＫｓｔｅｐ）在膜电位为＋４０ｍＶ时减少（３８±１０）％．尾电流步阶分析提示,ＩＫ的快组分（ＩＫｒ）和慢组分（ＩＫｓ）均被抑制．在犬浦肯野纤维,青蒿素明显抑制瞬时外向钾电流（Ｉｔｏ）,ＩＣ５０为（４．２±０．３）μｍｏｌ·Ｌ－１．实验结果表明,青蒿素以相似效率抑制ＩＫ１,Ｉｔｏ和ＩＫ,其抗心律失常作用可能与抑制ＩＫ１,Ｉｔｏ,ＩＫｒ和ＩＫｓ有关．     

甲基莲心碱对心肌细胞I_(Na)、I_(Ca-L)及稳态外向K~+电流的影响

目的　为证明甲基莲心碱（ Ｎｅｆｅｒｉｎｅ, Ｎｅｆ） 对单个心肌细胞离子通道电流的影响及抗心律失常作用的离子通道机制。方法　采用全细胞记录膜片钳技术,记录了 Ｎｅｆ 对培养大鼠心室肌细胞钠电流（ Ｉ Ｎａ） 及豚鼠心室肌细胞动作电位、 Ｉ Ｎａ 、 Ｌ 型钙电流（ Ｉ Ｃａ Ｌ） 及稳态外向 Ｋ＋ 电流的影响。结果　 Ｎｅｆ ３０ ,１００ μｍｏｌ· Ｌ－ １ 明显抑制培养大鼠心室肌细胞 Ｉ Ｎａ ,分别从对照水平的（３４ ±０７） ｎ Ａ 降至（２１ ±０５） 和（０４ ±０２） ｎ Ａ。 Ｎｅｆ １０ μｍｏｌ· Ｌ－ １ 可降低豚鼠心室肌细胞动作电位振幅、静息电位,延长动作电位时程。 Ｎｅｆ １０ ,３０ μｍｏｌ· Ｌ－ １ 分别使豚鼠心室肌细胞 Ｉ Ｎａ 及 Ｉ Ｃａ Ｌ从给药前的（７９ ±２１） ｎ Ａ 和（６８９ ±２４３） ｐ Ａ 降至（４０ ±１４） 、（１３ ±０６） ｎ Ａ和（３７４ ±１７２） 、（１０９ ±６７） ｐ Ａ。 Ｎｅｆ １０ μｍｏｌ· Ｌ－ １ 还抑制 Ｉ Ｎａ 、稳态外向 Ｋ＋ 电流和 Ｉ Ｃａ Ｌ的 Ｉ Ｖ 曲线并使后者的峰值电流电位略右移。结论　 Ｎｅｆ 有钠、 Ｌ 型钙通道阻滞作用并抑制稳态外向 Ｋ＋ 电流,这些可解释     

M 受体阻断剂对粉防己碱心肌负性肌力作用的调节及其离子机理

研究Ｍ 受体阻断剂对粉防己碱（Ｔｅｔ）负性肌力作用的影响并探讨其机理．记录Ｔｅｔ对豚鼠离体左心房收缩力,兔心房肌细胞动作电位及豚鼠单个心室肌细胞Ｃａ２＋ ,Ｋ＋ 通道电流的作用及Ｍ 受体阻断剂的影响．Ｍ 受体阻断剂阿托品（０．０３ μｍ ｏｌ·Ｌ－ １）及Ｍ２ 受体亚型阻断剂ＡＦ－ＤＸ １１６（１．０ μｍ ｏｌ·Ｌ－ １）能使Ｔｅｔ负性肌力作用的量效曲线平行右移, ＥＣ５０（μｍ ｏｌ·Ｌ－ １）由２８．９±０．９ 分别增至１２５±２１ 和１２７±１３;Ｔｅｔ（１－ １００ μｍ ｏｌ·Ｌ－ １）浓度依赖性缩短兔心房肌细胞动作电位时程ＡＰＤ２０,ＡＰＤ５０, 此作用被阿托品（０．０３ μｍ ｏｌ·Ｌ－ １）部分拮抗,而Ｔｅｔ延长ＡＰＤ９０ 的作用不受阿托品的影响．阿托品（１μｍ ｏｌ·Ｌ－ １）部分拮抗Ｔｅｔ（３０ μｍ ｏｌ·Ｌ－ １）对豚鼠心室肌细胞Ｌ－型钙电流的阻滞作用,而不影响其抑制内向整流钾电流（ＩＫ１）的作用． １ μｍ ｏｌ·Ｌ－ １乙酰胆碱则能逆转Ｔｅｔ对ＩＫ１的抑制．Ｍ 受体阻断剂对Ｔｅｔ阻滞钙通道作用的影响可能是其拮抗Ｔｅｔ负性肌力作用的主要离子机理．     

DDPH对豚鼠心室乳头状肌细胞电压与频率依赖性的电生理作用

目的　观察１ （２,６ 二甲基苯氧基） ２ （３,４ 二甲氧基苯乙氨基） 丙烷盐酸盐〔１ （２,６ ｄｉｍｅｔｈｙｌｐｈｅｎｏｘｙ） ２ （３ ,４ ｄｉｍｅｔｈｏｘｙｐｈｅｎｙｌｅｔｈｙｌａｍｉｎｏ） ｐｒｏｐａｎｅ ｈｙｄｒｏｃｈｌｏｒｉｄｅ, ＤＤＰＨ〕对豚鼠右心室乳头状肌细胞电压与频率依赖性的电生理作用。方法　采用常规细胞内玻璃微电极技术,分别以０－０２Ｈｚ、２ Ｈｚ 的刺激频率,观察ＤＤＰＨ（１ ～５０ μｍｏｌ·Ｌ－１） 对豚鼠右心室乳头状肌细胞动作电位（ＡＰ） 各参数的影响,并采用０－１ ～３－３ Ｈｚ 的刺激频率和提高Ｋ＋ 浓度（２－７ ～１５ ｍｍｏｌ·Ｌ－ １）将静息膜电位除极化到不同的水平,观察了ＤＤＰＨ（１０μｍｏｌ·Ｌ－１）对豚鼠右心室乳头状肌细胞动作电位零相最大除极化速率（ Ｖｍａｘ）频率与电压依赖性的抑制作用。结果　ＤＤＰＨ以浓度依赖降低豚鼠右心室乳头状肌细胞动作电位振幅（ＡＰＡ） 、缩短动作电位复极５０ ％ 时程（ＡＰＤ５０） 、延长动作电位复极９０％ 时程（ＡＰＤ９０） 并抑制Ｖｍａｘ ,但不明显改变静息膜电位（ＲＰ）,其作用在刺激频率为２ Ｈｚ 时较０－０２ Ｈｚ 时更为明显。对Ｖｍａｘ 呈现出刺激频率     

NAD-and NADP-dependent 11β-hydroxysteroid dehydrogenase isoforms in guinea pig kidney with gossypol inhibition

探讨棉酚诱发低钾血症机制．方法：从豚鼠肾脏皮质制备１１βＯＨＳＤ，反相高效液相测定该酶活性．结果：依赖辅酶Ｉ的１１βＯＨＳＤ的Ｖｍａｘ＝０６４ｍｍｏｌ·ｈ－１／ｇｐｒｏｔｅｉｎ，Ｋｍ＝００７μｍｏｌ；依赖辅酶ＩＩ的１１βＯＨＳＤ的Ｖｍａｘ＝１７５ｍｍｏｌ·ｈ－１／ｇｐｒｏｔｅｉｎ，Ｋｍ＝０２１μｍｏｌ．棉酚对它们的抑制有显著差异，ＩＣ５０（９５％可信限）前者为５０２（４８３－５２０）μｍｏｌ，后者为１１４３（１０９８－１１８８）μｍｏｌ，抑制常数Ｋｉ分别为９６ｍｍｏｌ·Ｌ－１和３４０ｍｍｏｌ·Ｌ－１．结论：抑制依赖辅酶Ｉ的１１βＯＨＳＤ是棉酚诱发低钾血症的更主要的生理因素．     

Electrophysiologic effect of enalapril on guinea pig papillary muscles in vitro

目的：研究依那普利（Ｅｎａ）对豚鼠乳头状肌电生理特性，哇巴因诱发的延迟后除极（ＤＡＤ）和触发电活动（ＴＡ）的直接作用．方法与结果：采用标准玻璃微电极技术记录豚鼠乳头状肌动作电位．Ｅｎａ呈浓度依赖性增加静息膜电位（ＲＰ）和动作电位幅度（ＡＰＡ），而对０期最大除极，超射，和动作电位时程无明显影响．Ｅｎａ１０μｍｏｌ·Ｌ－１则可明显抑制哇巴因０５μｍｏｌ·Ｌ－１诱发的ＤＡＤ和ＴＡ，ＤＡＤ幅度分别由５３±２３，５９±２８，７４±２１和８９±１３降至２６±０７，３１±１０，３７±１５和５３±１１（ｍＶ）（Ｐ均＜００１），刺激周长为２００ｍｓ时ＴＡ数目由３６±０７降至０８±０２（Ｐ＜００５）．结论：Ｅｎａ通过增加心肌细胞ＲＰ和ＡＰＡ抑制哇巴因诱发豚鼠乳头状肌ＤＡＤ和ＴＡ．     

Effects of norepinephrine and isopentenyladenosine on Na~ /Ca~(2 ) exchangecurrents in isolated guinea pig ventricular myocytes

目的：研究去甲肾上腺素（ＮＥ）和异丙肾上腺素（Ｉｓｏ）对Ｎａ＋／Ｃａ２＋交换电流的影响及受体调控机制．方法：应用全细胞电压钳技术的斜坡脉冲程序，测定离体豚鼠心肌细胞准稳态电流电压关系曲线．结果：ＮＥ０００５，００５和５μｍｏｌ·Ｌ－１分别使膜电位＋５０ｍＶ时的Ｎｉ２＋敏感电流增加２９％±９％，７２％±１１％和１２０％±３１％；Ｉｓｏ１５，１５０和１５００ｎｍｏｌ·Ｌ－１分别使该电流增加２８％±２８％，５６％±１３％和１０２％±１２％．ＮＥ和Ｉｓｏ的这种增强效应能被普萘洛尔１０μｍｏｌ·Ｌ－１完全阻断，而酚妥拉明５０μｍｏｌ·Ｌ－１无此作用．结论：ＮＥ和Ｉｓｏ通过兴奋心脏β肾上腺素受体使Ｎａ＋／Ｃａ２＋交换电流增加．     

Modulation of NMDA receptor by huperzine A in rat cerebral cortex 1

目的：研究石杉碱甲（ＨｕｐＡ）对大脑皮层ＮＭＤＡ受体的影响．方法：１）用急性分离海马锥细胞全细胞记录研究ＨｕｐＡ对ＮＭＤＡ诱发电流的影响．２）用大脑皮层突触膜标本研究ＨｕｐＡ对［３Ｈ］Ｄｉｚ特异性结合的影响．结果：１）ＨｕｐＡ可逆地抑制ＮＭＤＡ诱发的电流反应（ＩＣ５０＝４５４μｍｏｌ·Ｌ－１）．２）在突触膜标本,ＨｕｐＡ抑制［３Ｈ］Ｄｉｚ的结合量（ＩＣ５０＝０５（０１－１９）μｍｏｌ·Ｌ－１,ｎ＝４）．３）Ｌ谷氨酸１０μｍｏｌ·Ｌ－１增加［３Ｈ］Ｄｉｚ结合量．加入Ｌ谷氨酸后,ＨｕｐＡ０００１－０１μｍｏｌ·Ｌ－１进一步增加结合量;ＨｕｐＡ１－３００μｍｏｌ·Ｌ－１则抑制结合量（ＩＣ５０＝１２３（５８－２６３）μｍｏｌ·Ｌ－１,ｎ＝５）．结论：ＨｕｐＡ在大脑皮层除了抑制乙酰胆碱酯酶外,还是ＮＭＤＡ受体拮抗剂     

7－溴化乙氧苯四氢巴马汀对豚鼠心室肌细胞电压依赖性通道电流的影响

目的：研究７溴化乙氧苯四氢巴马汀（ＥＢＰ）对电压敏感通道电流的影响．方法：在豚鼠心室肌细胞上进行全细胞电流钳和电压钳记录．结果：ＥＢＰ３０μｍｏｌ·Ｌ－１可使单细胞ＡＰＤ９０从４３０±４７ｍｓ延长至５１４±６１ｍｓ（Ｐ＜００５，ｎ＝５）．电压钳研究表明ＥＢＰ可依剂量地抑制ＩＫ及其尾电流，而对ＩＫ１，ＩＣａ和ＩＮａ无明显作用．结论：以上结果提示选择性地抑制ＩＫ，从而延长动作电位时程，可能是ＥＢＰ抗心律失常作用机制之一．     

Artemisinin blocks activating and slowly activating K~ current in guinea pig ventricular myocytes

目的：研究青蒿素（Ａｒｔ）对豚鼠心室肌细胞外向整流钾电流的作用．方法：以全细胞膜片箝技术观察Ａｒｔ对快速延迟整流钾电流（ＩＫｒ）和缓慢延迟整流钾电流（ＩＫｓ）的作用．结果：Ａｒｔ剂量依赖性抑制时间依赖性外向钾电流（ＩＫｓｔｅｐ）和ＩＫｔａｉｌ．Ａｒｔ５０μｍｏｌ·Ｌ－１在＋４０ｍＶ时，使ＩＫｓｔｅｐ从３８７±４６ｐＡ减少到２４０±４８ｐＡ，ＩＫｔａｉｌ从２９９±３０ｐＡ减少到１３０±３８ｐＡ．结论：Ａｒｔ抑制外向钾电流的两种成分ＩＫｓ和ＩＫｒ．     

胃漂浮缓释片研究Ⅰ硝苯啶胃漂浮缓释片的制备与性质

以 PVP、PVA 为辅料制备了一种能漂浮在胃液上的硝苯啶片剂,用自制的石英弹簧秤比较了辅料配比不同时片剂的漂浮性能,片中硝苯啶以接近零级模式在8h 内释药90%。     

METABOLISM OF TETRADECAPEPTIDE, ANGIOTENSINOGEN AND ANGIOTENSIN I AND II BY ISOLATED PERFUSED RAT HINDLIMBS

1. We investigated the mechanism of tetradecapeptide-induced vasoconstriction by studying the metabolism of tetradecapeptide (TDP), angiotensinogen, and angiotensin I (AI) and angiotensin II (AII) by isolated perfused rat hindlimbs. 2. Using HPLC and specific RIAs we have quantified six angiotensin peptides: pentapeptide(4-8), hexapeptide(3-8), heptapeptide(2-8), octapeptide(1-8), nonapeptide(2-10) and decapeptide(1-10) in hindlimb effluent. 3. TDP-induced vasoconstriction was associated with generation of predominantly AI and AII, with smaller amounts of the other peptides measured. 4. Captopril prevented vasoconstriction and inhibited AII production by 80%, indicating a dominant role for AI generation in the vascular response to TDP. 5. Evidence that renin is not the enzyme responsible for AI generation from TDP includes: first, the failure of angiotensinogen to cause vasoconstriction or angiotensin peptide generation despite very high amounts of AI and AII generation from TDP; second, the resistance of the TDP-induced vasoconstriction and angiotensin peptide generation to inhibition by pepstatin; and third, the failure of bilateral nephrectomy 24 h before the experiment to influence the vascular and angiotensin peptide response to TDP. 6. AII was cleared with 41% efficiency, with generation of penta-, hexa-, and heptapeptides. 7. AI was cleared with 59% efficiency; this was reduced to 24% by captopril, indicating a conversion of at least 35% of AI to AII by ACE. 8. These studies have identified vascular metabolism of AI and AII to be an efficient process, with both ACE and aminopeptidases playing an important role, and indicate that those peptidases which cleave TDP to generate AI are unlikely to play any role in AI generation in vivo.     

免疫抑制剂I2190B的分离与鉴别

在筛选免疫抑制剂的过程中，找到了一株吸水类链霉菌Ｉ２１９０，属于ＦＫ－５０６类化合物的产生菌，从其发酵产物中已分离出Ａ、Ｂ二个组份，基于光谱数据和理化特性的分析，证实１２１９０Ｂ和免疫抑制剂ＦＫ－５２０及ＬＤ－６８３５９０（Ｉｍｍｕｎｏｍｙｃｉｎ）均为同一物质。     

新皮啡肽I(DELI)类似物的合成及构效关系研究

用固相多肽合成法合成了类阿片肽新皮啡肽I(DELI)及其三个类似物(将Asp4从5位到7位逐一后移)。实验发现DELI在离体条件(浓度范围10^-14～10mol·L^-1)和在体条件(剂量范围0.5～5μg·kg^-1)下能提高红细胞玫瑰花环形成细胞百分率(E-RFC)和红细胞C3b受体花环百分率(RBC-CR₁),且可被纳洛酮阻断。这些结果表明DELI能提高大鼠免疫功能。实验还发现DELI及其类似物的镇痛和免疫活性次序(由大到小)分别是Asp⁴,Asp⁷,Asp⁵,Asp⁶和Asp⁴,Asp⁷,Asp⁶,Asp⁵。     

马杜拉放线菌属新种的分类研究——Ⅰ:马杜拉放线菌新种和新变种

从我国福建省的土壤中分离到五株马杜拉放线菌,编号80-2、80-A13、80-30、80-28和80-191。其中除80-A13菌株外,其它菌株均有拮抗作用。无气生菌丝或气生菌丝贫乏,前二个菌株产生2～9个孢子的短孢子链,孢子表面疣状,后三个菌株孢子链形成假孢囊,孢子表面光滑。细胞壁化学组份为Ⅲ型,糖类型B,含马杜拉糖,甲基萘醌分析结果80-2为MK-9(H_6)、MK-9(H_8)。80-A13为MK-9(H_4)、MK-9(H_6),而80-30和80-191为MK-9(H_4)、MK-9(H_6)、MK-9(H_8)。通过分类研究证明它们不同于马杜拉菌属中的已知菌种。命名80-2为荧光马杜拉放线菌Actinomadura fluorescence sp.nov.1991;80-A13命名为微弱马杜拉放线菌Actinomaduraparva sp.nov.1991;80-30和80-28定名为紫褐马杜拉放线菌Actinomadura violacefonscussp nov 1991;80-191 定名为赭色马杜拉放线菌屏南变种Actinomadura ochracea varPingnansis nov.var.1991。     

CHANGES IN BLOOD AND RED CELL VOLUME IN THE NEONATAL LAMB AND THE EFFECT OF INSULIN-LIKE GROWTH FACTOR I

1. Blood volume was measured weekly using [⁵¹Cr]-labelled red cells in 10 lambs from 3 to 10 weeks of age. Red cell and plasma volumes were calculated using the measured blood volume and haematocrit. Other parameters, including plasma erythropoietin, urea, creatinine and glucose, were measured twice weekly. The results were compared to a group of five lambs that received an infusion of insulin-like growth factor I (IGF-I). 2. In control lambs, plasma volume increased linearly by 47 ± 7 mL/week over the experimental period. Red cell volume only increased by 10 ± 2 mL/week during weeks 3–7, but then increased by 25 ± 2 mL/week over weeks 7–10. Haematocrit declined from 28.0 ± 1.6 to 24.7 ± 1.7% over weeks 3–7 and then increased to 30.7 ± 1.1% by week 10. 3. In 10 control lambs infused for 8 days (starting at 22–26 days of age) with 10 mmol/L HCl, there was a decrease in plasma IGF-I concentrations, 3 days after the start of infusion. In five lambs infused for 8 days with IGF-I (6 μg/kg per h) plasma IGF-I concentration was maintained significantly (P < 0.01) higher than that of the controls. 4. There was no significant difference in haematocrit, red cell or plasma volumes between the treatment groups and no reticulocytosis was observed. Plasma erythropoietin concentrations did not change over the infusion period in either group. 5. Serum urea decreased significantly in the IGF-I infused group but serum creatinine did not change in either group during the infusion period. In both the groups, there was a significant decrease in glucose, urea and creatinine over weeks 3–10 after birth. There was no difference in growth rates between the two groups. 6. Thus, it appears that the observed changes in haematocrit are due to a constant increase in plasma volume with varying rates of red cell volume increases. 7. IGF-I infused at a dose that maintains physiological concentrations and alters protein metabolism does not result in increased erythropoietin or erythropoiesis during the neonatal period of the lamb.     

CIRCULATING LEVELS OF ACTIVE, TOTAL AND INACTIVE RENIN (PRORENIN), ANGIOTENSIN I AND ANGIOTENSINOGEN IN CARBON TETRACHLORIDE-TREATED RATS

1. Plasma renin activity (PRA), plasma angiotensin I concentration (ANG I), plasma angiotensinogen concentration (PAC) and the plasma levels of active, total and inactive renin (prorenin) were measured in rats with carbon tetrachloride (CCl₄)-induced acute renal failure. Rats were treated with a single oral dose of CCl₄ (2.5 mL/kg) and killed 1, 2, 3 and 7 days later. 2. On days 1–3 PRA, ANG I and PAC decreased and increased on day 7. Active renin fell on days 2 and 3, total renin (trypsin treatment) augmented on day 1 and diminished on day 3, prorenin and per cent prorenin increased on days 1 and 2. Angiotensin I concentration paralleled PRA and PAC. The CCl₄-induced decrease in PRA was secondary to the fall in active renin and in PAC. Total renin augmented as a consequence of the elevation of prorenin. Renal function, evaluated by serum urea, serum creatinine and creatinine clearance, decreased on days 1 and 2 when PRA was low and plasma prorenin was high. 3. These data do not support the involvement of the circulating active renin-angiotensin system (RAS) in the pathophysiology of acute renal failure induced by CCl₄, however, increased prorenin levels were associated with the decrease in renal function.