布美他尼对豚鼠离体气管平滑肌收缩功能的影响

目的研究布美他尼对Ｃａ２＋、组胺、乙酰胆碱、前列腺素引起豚鼠离体气管平滑肌收缩的影响。方法建立不同浓度Ｂｕｍｅｔ（１０－６、１０－５、１０－４ｍｏｌ·Ｌ－１）孵育时Ｃａ２＋和组胺量效曲线，观察Ｂｕｍｅｔ对Ａｃｈ和ＰＧＦ２α引起气管条收缩的抑制作用。结果Ｂｕｍｅｔ可压低Ｃａ２＋和Ｈｉｓ量效曲线，减活指数分别为３．０８±０．４８和５．６１±０．１３。对Ａｃｈ１０－５ｍｏｌ·Ｌ－１和ＰＧＦ２α５×１０－３ｍｏｌ·Ｌ－１引起的气管平滑肌收缩的ＩＣ５０分别为（５．０９×１０－６±０．１６×１０－６）ｍｏｌ·Ｌ－１和（５．１３×１０－６±０．１７×１０－６）ｍｏｌ·Ｌ－１。结论Ｂｕｍｅｔ可抑制Ｃａ２＋、组胺、乙酰胆碱、前列腺素Ｆ２α引起的豚鼠离体气管平滑肌收缩     

3－酮－地索高诺酮在家兔体内的药物动力学

以高效液相色谱分析法测定按２ｍｇ·ｋｇ－１剂量给家兔皮下注射３－酮－地索高诺酮后０．２５～２４ｈ的血药浓度，其血药浓度－时间曲线符合二室开放模型，药物动力学方程为Ｃ＝２５７．０７ｅ－０．７１ｔ＋４２．２３ｅ－０．０５ｔ－２９９．３０ｅ－０．９３ｔ主要药物动力学参数：Ｔｋａ０．７８±０．１７ｈ，Ｔα１．２０±０．３０ｈ，Ｔβ１２．０９±４．１８ｈ，ＡＵＣ１３１２．９０±３８７．４５μｇ·ｈ￣（－１）·Ｌ￣（－１），Ｔ＿（ｍａｘ）１．６９±０．３９ｈ，Ｃ（ｍａｘ）＝１２８．２１±５０·７１μｇ·Ｌ￣（－１），Ｖ／Ｆ９．５０±４．３９Ｌ·ｋｇ（－１）。采用平衡透析法测得３－酮－地索高诺酮与兔血浆蛋白的结合率在８１．０９％～８４．６０％之间。     

人生长激素治疗垂体性侏儒症的效力及安全性评价

目的：对生物合成人生长激素（ｈＧＨ）治疗垂体性侏儒症的效力及安全性进行评价。方法：垂体性侏儒症１６例，男性，其中１２例年龄１１±ｓ３ａ（７￣１５ａ），骨龄５±３ａ（２￣１０ａ），４例年龄１８．０±１．４ａ（１６￣１９ａ），骨龄１２．７±１．２ａ（１１￣１４ａ）。给予ｈＧＨ，每日剂量０．１ＩＵ／（ｋｇ·ｄ），ｓｃ，６￣１２ｍｏ。结果：骨龄≤１１ａ的年身高增长速率１１．０±１．２ｃｍ（Ｐ〈０．０５），     

IQ_(23)对豚鼠心室肌细胞钙通道和CHO H_(10)细胞异源表达的钙通道α_1亚单位的作用

应用膜片钳全细胞记录技术,观察了具有正性肌力作用的苄基异喹啉衍化物ＩＱ２３,即１－〔对甲氧苄基－２－（Ｎ－苄基,Ｎ－甲基）〕－６,７－二甲氧基异喹啉盐酸盐,对豚鼠心室肌分离细胞的Ｃａ２＋通道,以及ＣＨＯＨ１０细胞表达的Ｃａ２＋通道α１亚单位的作用．结果显示,当豚鼠心室肌细胞从保持电位（Ｖｈ）－５０ｍＶ除极至测试电位（Ｖｔ）０ｍＶ时,ＩＱ２３３,１０μｍｏｌ·Ｌ－１分别使Ｃａ２＋电流（ＩＣａ）由对照的（０．４７±０．２３）ｎＡ增至（０．５７±０．２３）和（０．７９±０．３１）ｎＡ（Ｐ＜０．０５）．在ＣＨＯＨ１０细胞Ｖｔ为２０ｍＶ时,ＩＱ２３１０μｍｏｌ·Ｌ－１电压依赖性的增强Ｂａ２＋电流（ＩＢａ）,ＩＢａ从（０．４５±０．１０）ｎＡ增至（０．６７±０．２０）ｎＡ（Ｖｈ＝－８０ｍＶ）,或从（０．４３±０．０８）ｎＡ增至（０．６０±０．１４）ｎＡ（Ｖｈ＝－４０ｍＶ）．ＩＱ２３１０和３０μｍｏｌ·Ｌ－１还分别使电流－电压曲线的峰值和失活曲线的半失活电位向负膜电位方向移动．实验结果表明,ＩＱ２３通过作用于通道的α１亚单位,对心肌Ｌ型Ｃａ２＋通道产生电压依赖性激动作用,此作用为其正性肌力效应提供了部分解释．     

萘普生控释片的人体相对生物利用度的研究

目的：研究８名健康志愿者口服萘普生片剂的药代动力学特征。方法：ＨＰＬＣ内标法测定人血浆中萘普生浓度，该法回收率＞８０％，日内及日间变异系数均＜１０％。结果：萘普生控释片与普通片的Ｔｍａｘ分别为８．３８±４．１４和２．３１±１．５１ｈ，Ｃｍａｘ分别为３７．１±５．８和５６．５±１０．１ｍｇ·Ｌ－１，ＭＲＴ分别为２０．５±１．７８和１６．５±１．１５ｈ，经检验差异均有显著性（Ｐ＜０．０５）；两制剂的ＡＵＣ０～４８分别为１０７１．１±１０６．１和１０２２．３±１１６．６ｍｇ·ｈ·Ｌ－１，控释片相对于普通片的生物利用度为１０５．３％±９．２２％，差异无统计学意义（Ｐ＞０．０５）。结论：该控释片具有明显的控释特征和临床使用价值。     

沙丁胺醇在家兔体内的时间药代动力学

沙丁胺醇（Ｓａｌ）抗哮喘作用的昼夜节律，可能与其在体内的药代动力学的昼夜差别有关。为此本文给家兔灌胃２ｍｇ·ｋｇ－１Ｓａｌ，用ＨＰＬＣ荧光检测１０：００ｈ和２２：００ｈ两个时间动物体内血药浓度。结果表明，Ｓａｌ的药动学参数存在明显的昼夜差别。Ｔｐ白天为（２．２８±０．２０）ｈ，夜间为（１．２５±０．３０）ｈ（Ｐ＜０．０５）；ＡＵＣ白天为（０．４１±０．０９）ｍｍｏｌ／Ｌ·ｈ，夜间为（０．３０±０．０５）ｍｍｏｌ／Ｌ·ｈ（Ｐ＜０．０５）；Ｔ１／２白天是（２．７２±０．２２）ｈ，夜间为（１．８６±０．１３）ｈ（Ｐ＜０．０５）；Ｃｍａｘ昼夜无差别。     

汉防己甲素抑制三种神经递质引起的新生大鼠脑细胞内游离钙的升高

应用Ｐｕｒａ－２技术测定游离新生大鼠脑［Ｃａ２＋］ｉ浓度的技术、研究了Ｔｅｔ对静息脑［Ｃａ２＋］ｉ和３种递质引起的脑［Ｃａ２］ｉ变化的影响。Ｔｅｔ（１，１０和２０μｍｏｌ·Ｌ－１）对静息脑［Ｃａ２＋］ｉ无明显影响。Ｔｅｔ（１０μｍｏｌ·Ｌ－１）可降低Ｌ－Ｇｌｎ（０．１、１．０和１０μｍｏｌ·Ｌ－１）引起的脑（Ｃａ２＋）ｉ的升高。在Ｈａｎｋ＇ｓ液Ｃａ２＋为１．３ｍｍｏｌ·Ｌ－１时，Ｔｅｔ１０μｍｏｌ·Ｌ－１可降低Ｈｉｓ（５０和１００μｍｏｌ·Ｌ－１）和５－ＨＴ（０．１、１．０、１０和１００μｍｏｌ·Ｌ－１）引起的脑［Ｃａ２＋］ｉ的升高。但不能降低Ｈａｎｋ＇ｓ液无Ｃａ２＋时Ｈｉｓ和５－ＨＴ引起的脑［Ｃａ２＋］ｉ的升高。研究表明Ｔｅｔ可阻滞Ｌ－Ｇｉｎ、Ｈｉｓ和５－ＨＴ受体调控的钙通道。但对Ｈｉｓ和５－ＨＴ引起的细胞内贮存钙的释放并无明显影响。Ｔｅｔ的这种降低脑［Ｃａ２＋］ｉ的作用可能是其治疗脑缺血性疾病的机理之一。Ｐ＜０．０１在Ｔｅｔ１０μｍｏｌ·Ｌ－１作用下，相同浓度的细胞外液钙和Ｈｉｓ（０、５０和１００μｍｏｌ·Ｌ－１），脑［Ｃａ２＋］ｉ分别是２２１±５、２４５±５和３０２±６ｎｍｏｌ·Ｌ－１。增加了１１．８?     

17β-雌二醇对人成骨细胞株HOS TE85细胞增殖及胞内cAMP,cGMP,iNOS影响

目的观察１７β－雌二醇（Ｅ２）对ＨＯＳＴＥ８５细胞增殖及胞内ｃＡＭＰ，ｃＧＭＰ，ｉＮＯＳ影响。方法［３Ｈ］－ＴｄＲ参入，放射免疫及Ｌ－３Ｈ－精氨酸转化法。结果Ｅ２１．０ｍｍｏｌ·Ｌ－１处理４８ｈ，细胞计数为（９４．３×１０７±７．５×１０７）个·Ｌ－１，对照组为（６５．０×１０７±５．９×１０７）个·Ｌ－１，［３Ｈ］－ＴｄＲ参入量增加４５．０％；细胞ｉＮＯＳ活性为（７３．０±６．６）ｐｍｏｌ·Ｌ－１·ｇ－１·ｍｉｎ－１（比对照组增加４６１．５％），ｃＧＭＰ为（０．６９±０．０３）ｐｍｏｌ·Ｌ－１·１０－８ｃｅｌ（比对照组增加３０５．９％）；抑制ｈＰＴＨ诱导胞内ｃＡＭＰ升高。结论Ｅ２能刺激成骨细胞增殖。Ｅ２可能通过影响胞内ｃＡＭＰ，ｃＧＭＰ，ｉＮＯＳ含量和活性而发挥作用。     

西拉普利的降压疗效

原发性高血压１４例（男性１０例、女性４例；年龄５３±ｓ８ａ）用西拉普利２．５ｍｇ，每晨顿服治疗，共４ｗｋ。结果：降压显效率５０％（７／１４），总有效率７１％。２４ｈ动态血压监测呈２４ｈ收缩压和舒张压显著的下降，在治疗期间没有发现明显的不良反应。＊ｐ＜０．０１。该药对降低ＳＢＰ有较明显的作用，并能维持２４ｈ降压效果。而对降低ＤＢＰ的效果不及前者明显。８例患者服药前２４ｈ平均ＳＢＰ负荷占５１％±１０％，２４ｈＤＢＰ负荷占５３％±７％：用药后２４ｈＳＢＰ负荷为３２％±１１％、２４ｈＤＢＰ负荷为３６％±８％。因此，平均ＳＢＰ及ＤＢＰ负荷下降均非常显著（Ｐ＜０．０５）。３心率改变情况用ＡＢＰＭ２４ｈ观察西拉普利服药前心率６８．０±１．４次／ｍｉｎ，服药后为６７０±１．１次／ｍｉｎ，变化不明显（Ｐ＞０．０５）。４症状改善情况症状改善依次为焦躁、疲倦、心悸、面红及头昏（表２）。表２１４例治疗前后自觉症状改善情况（例）５不良反应８例在服用本药１ｗｋ后，出现头昏、恶心，其中１例因此停药３ｄ，继续服药后症状消失，其余７例继续服药症状消失。１４例患者治疗前后血、尿常规，肝、肾功能，血糖，血脂，血清钾、钠、氯，心电图检查，无异常改?     

超氧阴离子对培养的牛动脉平滑肌细胞内钙及收缩性的影响

目的研究超氧阴离子对牛主动脉平滑肌细胞内钙及收缩性的影响。方法采用Ｆｕｒａ－２测定牛肺动脉平滑肌细胞内钙及采用胶原凝胶实验方法分析平滑肌细胞的收缩性。结果超氧阴离子作用于平滑肌细胞后使ＡＴＰ（１０μｍｏｌ·Ｌ－１）诱导的细胞内钙浓度的增加从（２０６± １０） ｎｍｏｌ·Ｌ－１降到（１４７±１５） ｎｍｏｌ·Ｌ－１。 ５ ｍｉｎ内细胞内钙浓度增加的积分（∫　△［Ｃａ２＋］ｉ·ｄｔ）从（１２．２± ０．５）μｍｏｌ· Ｌ－１·ｓ－１降至（９．８± ０．８）μｍｏｌ·Ｌ－１·ｓ－１。ｔｈａｐｓｉｇａｒｇｉｎ在无钙溶液中诱导的细胞内钙浓度的增加不受超氧阴离子的影响,而在含钙的Ｋｒｅｂａ溶液中,超氧阴离子能使随后的钙释放激活的钙进入（△［Ｃａ２＋］ｉＣＲＡＣ）从（２７．３ ±１．０） ｎｍｏｌ·Ｌ－１降到（１３．５ ±１．０） ｎｍｏｌ·Ｌ－１。ＡＴＰ诱导的凝胶面积减少的百分比从２４％±５％降到 ７．４％ ±０．２％;在无钙 Ｋｒｅｂｓ溶液中,ｔｈａｐｓｉｇａｒｇｉｎ诱导的凝胶面积减少的百分比从 ３．５％± ０．６％降到－０．５％±０．７％。结论超氧阴离子通过影响平滑肌细胞的内钙动员而降低它的收缩性。     

呋喃苯胺酸对Ca~（2＋）和几种致喘介质引起气管平滑肌收缩的抑制作用

在体外研究了呋喃苯胺酸对Ｃａ２＋和某些致喘介质对离体气管平滑肌收缩的影响。呋喃苯胺酸能明显压低Ｃａ２＋和组胺的量效曲线，ｐＤ２＇分别为２．８６±０．０３和２．８６±０．０４，对乙酰胆碱１０μｍｏｌ·Ｌ－１和前列腺素Ｆ２α５ｍｍｏｌ·Ｌ－１引起的气管条收缩也有一定抑制作用，ＩＣ５０分别为５．４±０．１６和１．５３×１０４±０．０９×１０４ｍｏｌ·Ｌ－１。     

一氧化氮供体预处理对乳鼠心肌细胞的延迟保护作用及其机制

目的　探讨一氧化氮模拟预处理延迟保护作用的机制。方法　体外培养新生大鼠心肌细胞 ,实验分为 :①阴性对照组 (Normal组 ) ;②SNAP组 :一氧化氮 (nitricoxide ,NO)供体S 亚硝基 N 乙酰青霉胺 (S nitroso N acetyl 1 ,1 penicil lamine ,SNAP ,5 0 0 μmol·L-1 )与心肌细胞共育 2 4h ;③Che +SNAP组 :蛋白激酶C拮抗剂白屈菜季铵碱 (chelerythrinechlo ride ,Che ,1 0 μmol·L-1 )处理心肌细胞 30min后 ,加入SNAP与心肌细胞共育 2 4h ;④PDTC +SNAP组 :核因子κB(NF κB)特异性阻断剂PDTC(1 0 0 μmol·L-1 )处理心肌细胞 30min后 ,加入SNAP与心肌细胞共育 2 4h ;⑤缺氧复氧损伤组 (H/R组 ) :心肌细胞缺氧 6h ,复氧 3h。②～④组部分取细胞爬片以免疫组织化学法观察SNAP对热休克蛋白 70 (HSP70 )表达的影响 ;其余细胞经历H/R损伤后 ,检测心肌细胞存活率及乳酸脱氢酶 (LDH)活性。结果　在正常心肌细胞免疫组织化学法未检测到HSP70的表达 ,心肌细胞经过H/R损伤后 ,可检测到少量HSP70阳性细胞 ,其阳性染色A值为 94 6± 9 1 ,心肌细胞培养上清LDH活性为 (2 1 90 5± 1 5 1 7)U·L-1 ,细胞存活率为 5 1 7%± 4 6 % ,细胞损伤较正常组加重 (P <0 0 1 ) ;SNAP处理细胞后 2 4h ,HSP70阳性细胞数增多 ,     

Metabolism of ochratoxin A: absence of formation of genotoxic derivatives by human and rat enzymes

Ochratoxin A (OTA) is a potent renal carcinogen in male rats, although its mode of carcinogenicity is not known. The metabolism and covalent binding of OTA to DNA were investigated in vitro with cytochromes P450, glutathione S-transferases, prostaglandin H-synthase, and horseradish peroxidase. Incubation of OTA with rat or human liver microsomes fortified with NADPH resulted in formation of 4-(R)-hydroxyochratoxin A at low rates [10-25 pmol min(-1) (mg of protein)(-1)]. There was no evidence of OTA metabolism and glutathione conjugate formation with rat, mouse, or human kidney microsomes or postmitochondrial supernatants (S-9) [<5 pmol min(-1) (mg of protein)(-1)]. Recombinant human cytochromes P450 (P450) 1A1 and 3A4 formed 4-(R)-hydroxyochratoxin A at low rates [0.08 and 0.06 pmol min(-1) (pmol of P450)(-1), respectively]; no oxidation products of OTA were detected with recombinant human P450 1A2 or 2E1 or rat P450 1A2 or 2C11 [<0.02 pmol min(-1) (pmol of P450)(-1)]. Prostaglandin H-synthase produced small amounts of an apolar product [33 pmol min(-1) (mg of protein)(-1)], and OTA products were not formed with horseradish peroxidase. There was no evidence of DNA adduct formation when [(3)H]OTA was incubated with these enzyme systems in the presence of calf thymus DNA (<20 adducts/10(9) DNA bases); however, these enzymes catalyzed DNA adduct formation with the genotoxins aflatoxin B(1), 2-amino-3-methylimidazo[4,5-f]quinoline, benzo[a]pyrene, and pentachlorophenol. There was also no detectable [(3)H]OTA bound in vivo to kidney DNA of male Fischer-344 rats treated orally with [(3)H]OTA (1 mg/kg, 100 mCi/mmol, 24 h exposure, <2.7 adducts/10(9) DNA bases), based upon liquid scintillation counting. However, (32)P-postlabeling experiments did show evidence of DNA lesions with total adduct levels ranging from 31 to 71 adducts/10(9) DNA bases, while adducts in untreated rat kidney ranged from 6 to 24 adducts/10(9) DNA bases. These results do not support the premise that OTA or metabolically activated species covalently bind to DNA and suggest that the (32)P-postlabeled lesions are due to products derived from OTA-mediated cytotoxicity.     

Role of cytochrome p4501 family members in the metabolic activation of polycyclic aromatic hydrocarbons in mouse epidermis

Polycyclic aromatic hydrocarbons (PAHs) are known to be activated by the cytochrome P450 (P450) 1 family. However, the precise role of individual P4501 family members in PAH bioactivation remains to be fully elucidated. We therefore investigated the formation of PAH-DNA adducts in the epidermis of Cyp1a2(-/-), Cyp1b1(-/-), and Ahr(-/-) knockout mice. A panel of different PAHs was used, ranging in carcinogenic potency. Mice were treated topically on the dorsal skin with the following tritium-labeled PAHs: dibenzo[a,l]pyre-ne (DB[a,l]P), 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (B[a]P), dibenzo[a,h]anthracene (DB[a,h]A), benzo[g]chrysene (B[g]C), and benzo[c]phenanthrene (B[c]P). At 24 h after treatment, mice (two male and two female mice per group) were sacrificed, and epidermal DNA was isolated and hydrolyzed with DNase I; subsequently, DNA adducts were quantitated by liquid scintillation counting. In the DB[a,l]P-treated mice, levels of DNA adducts were significantly lower in Cyp1a2(-/-) and Cyp1b1(-/-) mice by 57 and 46%, respectively, as compared to wild-type (WT) mice (C57BL/6 background). The levels of DB[a,l]P DNA adducts formed in Ahr(-/-) mice were 26% lower, but this was not statistically significant. The levels of DMBA-DNA adducts in Cyp1a2(-/-) mice were not different than the WT mice but were significantly lower in Cyp1b1(-/-) and Ahr(-/-) mice by 64 and 52%, respectively. DMBA-DNA adduct samples were further analyzed by HPLC following further digestion to deoxyribonucleosides. HPLC analysis of individual DMBA-DNA adducts revealed differences in the ratio of syn-DMBA-diol epoxide- to anti-DMBA-diol epoxide-derived adducts in the Ahr(-/-) and Cyp1b1(-/-) mice. The ratio of syn-/anti-derived adducts in WT mice was 0.49. This ratio was 0.23 in the Cyp1b1(-/-) mice and 0.87 in the Ahr(-/-) mice. In contrast to the results with DB[a,l]P and DMBA, the levels of B[a]P-, DB[a,h]A-, B[g]C-, and B[c]P-DNA adducts were significantly lower in Ahr(-/-) mice by 73, 75, 50, and 81%, respectively, as compared to WT mice but were not significantly lower in the Cyp1a2(-/-) or Cyp1b1(-/-) mice. Collectively, these and other results support a role for both P4501A1 and P4501B1 in the bioactivation of DMBA; P4501A2, P4501B1, and possibly P4501A1 in the bioactivation of DB[a,l]P; and P4501A1 in the bioactivation of B[a]P, DB[a,h]A, B[g]C, and B[c]P in mouse epidermis. Furthermore, in the metabolic activation of DMBA in mouse epidermis, P4501B1 shows a preference for the formation of syn-DMBA-diol epoxide adducts, whereas P4501A1 shows a preference for the formation of anti-DMBA-diol epoxide adducts.     

Aldo-keto reductase- and cytochrome P450-dependent formation of benzo[a]pyrene-derived DNA adducts in human bronchoalveolar cells

There is substantial evidence to suggest that polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (B[a]P) induce lung cancer through metabolic activation. As part of a program to delineate the routes of PAH activation, we have examined DNA adducts that are formed in human lung cells. A stable isotope dilution liquid chromatography/multiple reaction monitoring mass spectrometry method was used to quantify eight anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-B[a]P (B[a]PDE)-derived DNA adducts in four H358 human bronchoalveolar cell lines with different phenotypes. In P450 1A1/P450 1B1-induced H358 cells exposed to (+/-)-B[a]P-7,8-dihydro-7,8-diol (B[a]P-7,8-dihydrodiol), (+)-anti-trans-B[a]PDE-N2-2'-deoxyguanosine [(+)-anti-trans-B[a]PDE-N2-dGuo] was the major DNA adduct, and it formed with no lag phase. In AKR1A1-transfected H358 cells, (+)-anti-trans-B[a]PDE-N2-dGuo was also the major adduct with a 3 h lag phase before significant adduct formation was detected. In AKR1A1-transfected H358 cells with induced P450 1A1/P450 1B1, (+)-anti-trans-B[a]PDE-N2-dGuo was formed with no lag phase in amounts similar to those in the H358 cells with up-regulated P450 1A1/P450 1B1. Surprisingly, the greatest amount of (+)-anti-trans-B[a]PDE-N2-dGuo was formed in the control H358 cells. Furthermore, (+)-anti-trans-B[a]PDE-N2-dGuo formation was 2-fold higher in (-)-B[a]P-7,8-dihydrodiol-exposed H358 cells when compared with (+/-)-B[a]P-7,8-dihydrodiol-exposed cells. The P450 1A1/1B1 inhibitor 2,4,3',5'-tetramethoxystilbene did not attenuate DNA adduct formation in the control H358 cells, suggesting that another P450 was responsible. These data raise the intriguing possibility that P450 1A1/P450 1B1 and AKR1A1 may be protective against (+)-B[a]PDE-mediated DNA damage.     

不同剂量卡托普利对自发性高血压大鼠左心室肥厚逆转作用比较

观察了小剂量卡托普利（Ｃａｐ）是否能在血压无明显下降情况下逆转自发性高血压大鼠（ＳＨＲ）的左心室肥厚。已有左心室肥厚的ＳＨＲ经Ｃａｐ２０ｍｇ·ｋｇ￣（－１）·ｄ￣（－１）治疗２４ｗｋ后血压仍维持在给药前水平，左心室重和体重的比值轻度下降，Ｃａｐ５０ｍｇ·ｋｇ￣（－１）·ｄ￣（－１）治疗２４ｗｋ后血压，左心室重和体重的比值均低于给药前水平，但仍未达正常水平。两种剂量的Ｃａｐ对心肌内去甲肾上腺素和羟脯氨酸含量及血小板内游离钙离子的影响基本相同。长期小剂量Ｃａｐ治疗即使在血压没有明显下降情况下仍能防止左心室肥厚发展，甚至还有轻度逆转ＳＨＲ的左心室肥厚和减少心脏胶原的作用。大剂量Ｃａｐ除减少心脏胶原外，还有明显的逆转左心室肥厚的作用，Ｃａｐ的降压和逆转左心室肥厚作用有相关性。     

利福平对家兔静注安替比林药代动力学的影响

选用健康家兔，分析利福平引起的静注安替比林药代动力学的改变，同时定量评估利福平对肝药酶活性的影响。实验结果表明利福平可使安替比林半衰期有所缩短；清除率由９．９±２．８ｍｌ·ｋｇ－１显著增加至１７．１±７．０ｍｌ·ｋｇ－１·ｍｉｎ－１，平均增加７２％；ＡＵＣ由１０７６．１±２８８．２显著减少至６８３．２±２８９．０ｍｇ·Ｌ－１·ｍｉｎ－１。因此，利福平可加速药物的代谢和排泄，说明利福平可显著提高肝药酶的活性；应用四点方法与３Ｐ８７计算主要药代参数两者无显著差异。提示，当药物消除符合一室模型（或所取数据点在消除相）时，可用该法计算有关的药代参数。     

阿卡波糖对2型糖尿病病人胰岛素抵抗的影响

目的 :探讨阿卡波糖对 2型糖尿病病人胰岛素抵抗的影响。方法 :16 0例 2型糖尿病病人随机分为 2组 ,治疗组 80例口服阿卡波糖治疗 ,前 2wk ,5 0mg ,po ,tid ,2wk后 ,10 0mg ,po ,tid ;安慰剂组 80例口服安慰剂 ,方法同治疗组 ,疗程为 2 4wk。同时观察空腹及餐后 2h血糖、血清胰岛素水平、体重指数、糖化血红蛋白、空腹时的红细胞胰岛素受体和红细胞膜流动性治疗前后变化。结果 :(1)wk 4时 ,阿卡波糖明显降低病人的空腹血糖、餐后 2h血糖、糖化血红蛋白 ,下降值分别为 :(2 .9±s 0 .8)mmol·L- 1,(4.0± 1.8)mmol·L- 1,(1.2± 2 .1) % ,P<0 .0 1;(2 ) 2 4wk后 ,阿卡波糖降低病人的体重、空腹血清胰岛素、餐后 2h血清胰岛素 ,下降值分别为 :(6± 4 )kg·m- 2 ,(10± 6 )MIU·L- 1,(14± 10 )MIU·L- 1,增加红细胞胰岛素受体 ,升高值为 :(80± 71)sites·RBC- 1,降低膜流动性 ,下降值为 :(1.5± 1.3) ,P <0 .0 1。结论 :阿卡波糖能改善 2型糖尿病病人的胰岛素抵抗     

卡托普利对培养乳鼠心肌细胞蛋白质合成的抑制作用

以培养乳鼠心肌细胞作为模型，观察了卡托普利对心肌细胞生长的抑制作风结果表明。卡托普利２０和２００ｕｍｏｌ·Ｌ￣（－１）作用于细胞７２ｈ，心肌细胞的总蛋白质量分别减少９％和１８％。但细胞数目未见明显变化。用［￣３Ｈ］亮氨酸结合的方法，测得血管紧张素Ⅱ１，１０．１００ｎｍｏｌ·Ｌ￣（－１）在４８ｈ内增加蛋白质合成２９％。５３％和７０％，但用［￣３Ｈ］胸腺嘧啶核苷结合的方法测得ＤＮＡ的合成未见明显增加。无论１００ｎｍｏｌ·Ｌ￣（－１）血管紧张素Ⅱ是否存在，卡托普利２０和２００ｕｍｏｌ·Ｌ￣（－１）均能够减少细胞的蛋白质合成。结果提示卡托普利可以直接抑制心肌细胞的生长。此作用可能与其抑制心肌肥厚有关。