氯喹、地塞米松对烟雾吸入伤大鼠肺细胞膜损伤的影响

目的　观察氯喹、地塞米松对烟雾吸入伤大鼠肺细胞膜损伤的影响。方法　健康 Ｗｉｓｔａｒ 大鼠１００ 只随机分成正常对照组,吸入伤１ ｈ 、３ ｈ 、６ ｈ 、１２ ｈ 和２４ ｈ 组,氯喹治疗６ ｈ和１２ ｈ 组以及地塞米松治疗６ ｈ 和１２ ｈ 组。实验毕活杀动物,取肺组织制备细胞膜。提取膜磷脂,并用高效液相色谱仪测定磷脂组份,用荧光偏振法测定膜流动性,用生化比色法测定细胞膜 Ｎａ＋ , Ｋ＋ Ａ Ｔ Ｐ 酶、 Ｃａ２ ＋ Ａ Ｔ Ｐ 酶和 Ｍｇ２ ＋ Ａ Ｔ Ｐ酶活性。结果　烟雾吸入伤后,细胞膜磷脂酰胆碱（ Ｐ Ｃ） 、磷脂酰乙醇胺（ Ｐ Ｅ） 和磷脂酰肌醇（ Ｐ Ｉ） 明显降低,同时伴有膜荧光偏振度（ρ） 和膜平均微粘度（η） 明显增加及３ 种 Ａ Ｔ Ｐ 酶活性降低（ Ｐ＜ ００５ ～ Ｐ＜ ００１） 。与吸入伤６ ｈ 组相比,氯喹治疗６ ｈ 组动物 Ｐ Ｃ、 Ｐ Ｅ 含量明显增加,同时降低ρ和η,并增加 Ｎａ ＋ , Ｋ＋ Ａ Ｔ Ｐ 酶和 Ｃａ２ ＋ Ａ Ｔ Ｐ 酶活性（ Ｐ＜ ００５ ～ Ｐ＜ ００１） ,而地塞米松治疗６ ｈ 动物仅增加 Ｐ Ｅ 含量、降低ρ和η,但对膜上 Ａ Ｔ Ｐ 酶活性无影响。结论　烟雾吸入可引起肺细胞膜受损,膜流动性及膜 Ａ Ｔ Ｐ 酶活性降低,而氯?     

氯喹对烟雾吸入伤大鼠肺细胞膜ATP酶活性和丙二醛含量的影响

目的：探讨氯喹对烟雾吸入伤大鼠肺细胞膜ＡＴＰ酶活性及丙二醛含量的影响,方法：８０只Ｗｉｓｔａｒ大鼠随机分成正常对照组,烟雾吸入伤１,３,６,１２和２４ｈ组以及氯喹治疗６ｈ和１２ｈ组,分别于各时相点活杀动物,取肺制备膜制剂,用生化比色法测定膜上Ｎａ＾＋,Ｋ＾＋－ＡＴＰ酶Ｍｇ＾２＋－ＡＴＰ酶和Ｃａ＾２＋－ＡＴＰ酶活性,用比色法测定膜上丙醛含量,并用定磷法测定膜总磷脂含量,结果：烟雾吸入伤后,肺细胞膜３     

犬吸入性损伤吸入一氧化氮对某些内源性血管活性物质的影响

目的旨在评价吸入外源性ＮＯ对几种主要内源性缩血管活性物质的影响。方法以烟雾吸入性损伤犬模型为研究对象，１７只犬随机分为２组，对照组（ｎ＝８）单纯吸氧（ＦｉＯ２，０．４５），治疗组（ｎ＝９）吸氧（ＦｉＯ２，０．４５）＋０．００４５％（４５×１０－６）ＮＯ，连续监测１２ｈ动脉血变化。数据进行多个样本均数间方差分析。结果伤后两组血浆内皮素（ＥＴｓ）、血管紧张素Ⅱ（ＡⅡ）、肾上腺素（Ｅ）和去甲肾上腺素（ＮＥ）含量均明显升高，治疗组在治疗开始后，与对照组相比均有不同程度降低，ＥＴｓ（Ｐ＜０．０５，０．０１），ＡⅡ（Ｐ＜０．０５，０．０１），Ｅ（Ｐ＜０．０５，０．０１），ＮＥ（Ｐ＜０．０１）。结论吸入外源性ＮＯ对内源性缩血管活性物质有不同程度抑制作用，提示临床应用吸入ＮＯ疗法应逐渐减量，以防发生反跳。     

小檗碱对大鼠实验性心肌梗塞的保护作用

应用大鼠实验性心肌梗塞模型，观察小檗碱（Ｂｅｒｂｅｒｉｎｅ，Ｂｅｒ）对缺血心肌的保护作用。结果表明；Ｂｅｒ（总量１２ｍｇ·ｋｇ－１，ｉＰ）能显著缩小大鼠冠脉结扎后２４ｈ的心肌梗塞范围，减少血清游高脂肪酸的增高，降低梗塞后病理性Ｑ波的发生率，提示Ｂｅｒ对缺血心肌具有保护作用。Ｐ＜０．０１（ｎ＝１０），３０６±８７μｍｏｌ·Ｌ－１（ｎ＝１０），与正常血清比差异无显著性（Ｐ＞０．０５），ＮＳ组冠脉结扎后１ｈ，４ｈ血清ＦＦＡ明显增高，与结扎前正常血清比差异有显著性（Ｐ＜０．０５）。Ｂｅｒ和Ｖｅｒ组与ＮＳ组比均能降低冠脉结扎后１ｈ，４ｈ血清ＦＦＡ的增高（Ｐ＜０．０５）。结果见表２。表２Ｂｅｒ对大鼠冠脉结扎后１ｈ，４ｈ血清ＦＦＡ的影响，ｎ＝１０；与ＮＳ组比较，Ｐ＜０．０５２．３对大鼠心肌梗塞后病理性Ｑ波的影响各组大鼠结扎后４ｈ，２４ｈ胸前导联（Ｖ４）心电图病理性Ｑ波的出现率见表３。结果表明，Ｂｅｒ与Ｖｅｒ相似，能降低Ｑ波的发生率（Ｐ＜０．０５）。表３Ｂｅｒ对大鼠冠脉结扎后４ｈ，２４ｈＥＣＧＱ波发生率的影晌（ｎ＝１０）Ｓｈａｍ＝伪结扎组，与ＮＳ组比较，＊Ｐ＜０．０５，Ｐ＜０．０１３讨论ＭＩＳ是影响心功能的主要因素之一，Ｍ?     

顺铂对大鼠红细胞免疫初步研究

采用ＤＤＰ于大鼠尾静脉一次性注射，同时设正常对照及中药组，６周后观察对红细胞免疫功能的影响。结果发现ＤＤＰ可致红细胞Ｃ３ｂ受体花环率降低（Ｐ＜０．０１）；免疫复合物花环率升高（Ｐ＜０．０５）。而中药组红细胞Ｃ３ｂ受体花环率明显高于ＤＤＰ所致的模型组（Ｐ＜０．０１）。提示，中药对ＤＤＰ所致的红细胞免疫功能损伤具有较好的修复作用。     

中期妊娠药物引产不同给药途径的效果观察

目的：探索米非司酮配伍米索前列醇（米索）终止１６周～２４周妊娠的最佳给药途径。方法：将２４０例孕１６周～２４周要求终止妊娠的妇女随机分为２组，观察组１３０例．米非司酮５０ｍｇ每天二次，连服３ｄ（总量３００ ｍｇ），第４天晨阴道内放置米索２００μｇ，２ ｈ～３ｈ１次．２４ ｈ内最多６次；对照组１１０例，米非司酮用法同观察组，第４天晨口服米索４００μｇ，以后隔２ｈ～３ ｈ服药１次，２４ ｈ内可服４次．两组若２４ｈ内宫口未扩张第２天均可重复用药。结果：两组４８ｈ内的引产成功率分别为９９．２３％和９８．１８％．差异无显著性（Ｐ＜０．０５），２４ｈ小时内流产成功者米索的用量．阴道给药者比口服给药者明显减少（Ｐ＜０．０１）．胃肠道副反应发生率也明显降低（Ｐ＜０．０５）。结论：米索２００μｇ阴道小量序贯给药是中期引产较好的给药方法。     

甲状腺功能状态对普萘洛尔药物动力学的影响

本文通过建立具有亚临床病例特点的实验性甲亢和甲低模型，以及通过参照文献的方法建立应用荧光分光光度计测定血浆中普萘洛尔（ｐｒｏｐｒａｎｏｌｏｌ）的方法，研究了甲状腺功能状态对普萘洛尔药物动力学的影响。结果如下：对照组，甲亢组和甲低组大鼠ｉｐ普萘洛尔４ｍｇ／ｋｇ，求得其主要药物动力学参数：Ｔ１／２β（ｈ）分别为４．５４±０．６５，３．５８±０．３５（Ｐ＜０．０５）和６．４±０．８（Ｐ＜０．０５）；Ｋ１０（ｈ－１）分别为０．９９±０．０２，１．２３±０．０９（Ｐ＜０．０１）和０．６６±０．０８（Ｐ＜０．０１）；ＡＵＣ〔ｎｇ／（ｍｌ·ｈ）〕分别为６５４．２±９０．４，４４８．２±６６．８（Ｐ＜０．０１）和１０３４．６±１３２．３（Ｐ＜０．０１）；ＣＬ〔ｍｇ／（ｋｇ·ｈ）／（ｎｇ·ｍｌ）〕分别为０．００６２２±０．０００９６，０．００９１±０．００１６（Ｐ＜０．０１）和０．００３９２±０．０００５８（Ｐ＜０．０１）；Ｃｍａｘ（ｎｇ／ｍｌ）分别为５０１．４６±４０．１３，４０８．３３±５７．６５（Ｐ＜０．０１）和６０７．８±２７．２（Ｐ＜０．０１）。     

速克喘干粉吸入剂在慢性阻塞性肺疾病急性发作期的作用

目的：了解速克喘干粉吸入剂在慢性阻塞性肺疾病（ＣＯＰＤ）急性发作期的作用。方法：ＣＯＰＤ急性发作期３０例（男性２１例，女性９例，年龄６９±ｓ６ａ），用速克喘吸入４００μｇ。结果：临床总有效率为７５％，吸入后５ｍｉｎ肺功能即有明显改善，２ｈ后用力肺活量，１ｓ用力呼气量和最大呼气流速有明显增加（Ｐ＜０．０５，Ｐ＜０．０１），有效时间达４ｈ以上。无明显不良反应。结论：ＣＯＰＤ急性发作期病人用速克喘可缓解胸闷、气急等症状。     

烧伤病人红细胞七项指标的变化

采用ＳｙｓｍｅｘＦ－８００型全自动血液分析仪随机对８８例中度以上烧伤病人伤后１、３、７、１４、２１天红细胞七项指标进行动态观察，结果显示：中度、重度、特重度三级不同伤情的烧伤病人伤后早期红细胞计数、血红蛋白、红细胞压积较健康人增高（Ｐ＜０．０５），红细胞平均容积、红细胞平均血红蛋白含量、红细胞平均血红蛋白浓度、红细胞体积分布宽度则无显著改变（Ｐ＞０．０５），而从伤后第７天开始三组病人前三项指标明显降低（Ｐ＜０．０５或０．０１），红细胞体积分布宽度亦出现较明显升高（Ｐ＜０．０５或０．０１）。     

颅脑损伤后不同时期用脑活素治疗

重型颅脑损伤１５８例中，４８例（男性４０例。女性８例；年龄２６±ｓ８ａ）用常规治疗，１１０例（男性９６例，女性１４例；年龄２８±１１ａ）于伤后６－８ｈ，２４－３６ｈ和７２ｈ开始加用脑活素１０－２０ｍＬ于０．９％氯化钠溶液２５０ｍＬ静脉滴注，ｑｄ，分别２９±４．３０±６，２８±８次。结果：伤后６－８ｈ开始用脑活素组疗效最佳（Ｐ＜０．０１）。     

苄达赖氨酸片剂在家犬体内药代动力学和相对生物利用度

目的：比较苄达赖氨酸两种片剂在家犬体内的药代动力学和相对生物利用度。方法：高效液相—荧光检测法。结果：家犬口服后，其体内的血药浓度—时间曲线符合一室开放模型。国产片和进口片的主要药动学参数分别为Ｃｍａｘ：１３．７８±１．８６ｍｇ·Ｌ－１和１４．０±１．５０ｍｇ·Ｌ－１；Ｔｍａｘ：６．２４±０．５９ｈ和６．３９±０．８２ｈ；ＡＵＣ：８８３．２８±１５６．３５ｍｇ·ｈ－１·Ｌ－１和９０５．１０±１７３．８０ｍｇ·ｈ－１·Ｌ－１。结论：国产苄达赖氨酸片剂对进口苄达赖氨酸片剂的相对生物利用度为９７．９９％±５．８７％，可以认为国产片与进口片生物等效。     

单剂量口服法莫替丁缓释片的药代动力学

选择６名男性健康志愿者，通过ＨＰＬＣ法测定单剂量口服法莫替丁缓释片和普通市售片后的血药浓度，用３ｐ８７程序处理数据，研究该药缓释制剂的药代动力学和生物利用度，并考察了体内吸收率与体外溶出度的相关性．结果表明，两种剂型在体内血药浓度－时间曲线均符合一室模型．法莫替丁缓释片的主要药代动力学参数为：Ｔｍａｘ＝４．６ｈ，Ｃｍａｘ＝５０．９６μｇ／Ｌ，Ｔ１／２ｋｅ＝５．０４ｈ，ＡＵＣ＝６９６．８６μｇ·ｈ／Ｌ．其相对生物利用度为１１６％．     

Alleviation of wood smoke-induced lung injury by tachykinin receptor antagonist and hydroxyl radical scavenger in guinea pigs

We recently reported that wood smoke inhalation initially (within 5 min) causes airway injury and subsequently produces both airway and parenchymal injury after a delay (within 2 h). In this study, we investigated the mediator mechanisms of this delayed smoke-induced lung injury in 126 anesthetized and artificially ventilated guinea pigs who received challenges of either air or 40 tidal breaths of wood smoke. Two hours after inhalation, wood smoke produced various injurious responses, including increases in alveolar-capillary permeability, microvascular permeabilities, and histological injury scores, in airway and parenchymal tissues. Pre-treatment given before smoke challenge with CP-96,345 [a tachykinin NK1 receptor antagonist; (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-aza bicyclo(2.2.2.)-octan-3-amine], dimethylthiourea (a hydroxyl radical scavenger), or a combination of these two drugs largely alleviated both the airway and parenchymal responses, whereas pre-treatment with SR-48,968 [a tachykinin NK2 receptor antagonist; (S)-N-methyl-N(4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-butyl)benzamide] or a combination of CP-96,344 and SR-48,965 (inactive enantiomers) failed to do so. Post-treatment given at 5 min after smoke challenge with CP-96,345 or dimethylthiourea significantly alleviated the parenchymal responses, while having no effect on the airway responses. Pre-treatment with dimethylthiourea prevented the smoke-induced reduction in airway neutral endopeptidase activity (an enzyme for tachykinin degradation). We concluded that (1) tachykinins and hydroxyl radical play important roles in producing smoke-induced delayed lung injury in guinea pigs, and both may be involved in the spread of injury from the airways to the pulmonary parenchyma, and (2) the contribution of tachykinins is mediated via the activation of tachykinin NK1 receptors, and is associated with the hydroxyl radical-induced inactivation of airway neutral endopeptidase.     

A rat model of smoke inhalation injury

Context: Smoke inhalation injury is the leading cause of acute respiratory failure in critical burn victims. Advances in the treatment of smoke inhalation injury have been limited in the past years. To further explore the pathogenesis, stable and practical animal models are necessary.

Objective: To develop a rat model of smoke inhalation injury.

Materials and methods: The smoke composition including the particulate matters, irritant gases, chemical carcinogens was measured. The blood gas values, pro-inflammatory and protein concentration in bronchoalveolar lavage fluid and lung wet to dry weight ratio were assayed. Pathological evaluations of pulmonary were performed at 24 h, 96 h, 7 days and 28 days post-injury. Masson–Goldner trichrome staining was performed on day 7 and 28 post-injury, along with the measurement of hydroxyproline and collagen I and III.

Results: In our present animal model, smoke inhalation caused a significant hypoxemia and CO poisoning. A surge of pro-inflammatory response and microvascular hyperpermeability with neutrophils accumulations were also found in our animal model. At 24 h post-smoke inhalation, the hematoxylin and eosin results exhibited that there were inflammatory exudates and diffuse hemorrhage in the lung tissue with significant edema. With the time going, the lung injuries appeared at alveolar collapse and alveolar septum thickening, which indicated that smoke inhalation further induced damage to lung parenchyma. Specially, the markedly collagen deposition appeared at 28 days post-injury indicated that pulmonary fibrosis happened.

Discussion and conclusion: In conclusion, this rat smoke inhalation injury model induced by our novel self-made smoke generator could be used for acute and chronic lung injury experiments.     

芸香甙的药代动力学研究

目的研究芸香甙在兔体内的药代动力学。方法家兔一次静注芸香甙５ｍｇ·ｋｇ－１后，利用荧光分光光度法测定不同时间的血药浓度。应用３Ｐ８７药动学软件程序对数据进行计算机处理。结果芸香甙的药时（Ｃ－Ｔ）方程为：Ｃ＝８５．９７８９ｅ－０．９０４４Ｔ＋３４．５１０５ｅ－０．０５８７Ｔ＋４．３８３８ｅ－０．００４６Ｔ。芸香甙的主要药代动力学参数如下：Ｔ１／２ａ：（０．７６０９±０．１０６６）ｍｉｎ，Ｔ１／２ｂ：（１２．５６６７±３．７１３９）ｍｉｎ，Ｔ１／２ｃ：（１６２．５６５１±５０．６０３５）ｍｉｎ，Ｋ１２：（０．５１２３±０．１３１６）ｍｉｎ－１，Ｋ２１：（０．３２９８±０．０７３７）ｍｉｎ－１，Ｋ１３：（０．０７３９±０．０１８２）ｍｉｎ－１，Ｋ３１：（０．０１００±０．００３７）ｍｉｎ－１，Ｋ１０：（０．０７７４±０．０１６０）ｍｉｎ－１，Ｖｃ：（０．０４０４±０．００４４）Ｌ·ｋｇ－１，ＡＵＣ：（１６７９．７５８３±４８０．６０４５）ｍｇ·Ｌ－１·ｍｉｎ－１，ＣＬ（ｓ）：（０．００３１±０．０００８）Ｌ·ｋｇ－１·ｍｉｎ－１。结论芸香甙在兔体内的Ｃ－Ｔ变化符合三室开放模型；芸香甙在体内的分布、消除迅速。     

赛庚啶对大鼠垂体-甲状腺轴功能的影响

目的研究赛庚啶对大鼠垂体－甲状腺轴内分泌功能的影响。方法用放射免疫分析法和电镜观察赛庚啶对大鼠垂体－甲状腺轴内分泌功能及垂体ＴＳＨ细胞超微结构的影响。结果赛庚啶２．３ｍｇ·ｋｇ－１，ｉｇ，连续用药１０ｄ，可使大鼠血清促甲状腺激素（ＴＳＨ）含量明显降低（Ｐ＜０．０５），而甲状腺激素（Ｔ３，Ｔ４）则无显著变化。４．６ｍｇ·ｋｇ－１赛庚啶可引起大鼠血清ＴＳＨ，Ｔ３，Ｔ４水平均显著降低（Ｐ＜０．０１及０．０５），组织形态电镜观察，该药亦引起大鼠垂体ＴＳＨ细胞超微结构的退行性改变。结论赛庚啶对大鼠垂体－甲状腺轴的内分泌功能有抑制作用。     

ACUTE PULMONARY RESPONSE TO INHALED JP-8 JET FUEL AEROSOL IN MICE

The pulmonary response to JP-8 jet fuel inhalation was investigated by characterizing biomarkers of lung injury, respiratory permeability, pulmonary function, and lung morphology. C57BL/6 and B6.A.D. (Ahrd/Nats) mice, aryl hydrocarbon hydroxylase nonresponsive and slow N -acetylator, were exposed to atmospheres ranging from 0 to 113 mg/m 3 of aerosolized JP-8 jet fuel for 1 h. At 24-30 h after the exposure, pulmonary function testing was performed on anesthetized animals. Respiratory permeability was measured by monitoring the pulmonary clearance of instilled 99 m Tc-labeled diethylenetriamine pentaacetate and then lungs were assigned for bronchoalveolar lavage or histopathology. Bronchoalveolar lavage fluid (BALF) was analyzed for total protein, lactate dehydrogenase (LDH), and N -acetyl--D-glucosaminidase (NAG) as well as cell number and type. Pulmonary responses to JP-8 were similar in both strains of mice. JP-8 exposure between 50 and 113 mg/m 3 caused an increase in respiratory permeability, which was accompanied by BALF increases of total protein, LDH, NAG, and alveolar macrophages. There was also a small increase in BALF neutrophils in the C57BL/6 strain. JP-8 exposures did not have an effect on pulmonary function even though histopathology showed evidence of terminal bronchiole lesions. These results indicate that the acute pulmonary response to permissible exposure levels of aerosolized JP-8 jet fuel can cause changes in respiratory permeability and BALF markers of lung injury. These changes in biochemical, cellular, and pathological parameters following JP-8 exposure provide evidence that occupational exposure to hydrocarbon fuel aerosol is more detrimental than vapor exposure.     

A study of 99mtechnetium-labelled beclomethasone dipropionate dilauroylphosphatidylcholine liposome aerosol in normal volunteers

^99mTechnetium (^99mTc) was bound to preformed beclomethasone dipropionate (Bec) dilauroylphosphatidylcholine (DLPC) liposomes (Bec-DLPC) in the presence of the reducing agent, stannous chloride. Labelling efficiency was 96–99% as determined by micropartition and chromatographic analysis. Andersen cascade impactor analysis showed close correlation of the distribution of ^99mTc, DLPC, and Bec over the full range of particle sizes sampled. In mouse biodistribution studies, approximately one-half of ^99mTc activity delivered to the lungs was retained at 24 h. ^99mTc clearance was almost exclusively via the gastrointestinal tract. In contrast, free ^99mTc (administered unbound to Bec-DLPC) liposomes was cleared from mouse lungs within a few minutes. Six normal volunteers inhaled 20 breaths of the labelled Bec-DLPC liposome aerosol from each of two nebulizers (Aerotech II, MMAD 1.5μ, GSD 2.4) (Spira, MMAD 3.6μ, GSD 2.5). Immediately following inhalation, the gamma camera analysis showed 17% pulmonary deposition of inhaled ^99mTc-Bec-DLPC with the Aerotech II and 14% with the Spira nebulizer. At 3 h after Aerotech II exposure, 93% of deposited activity was retained in the lung and 82% was retained from the Spira nebulizer. These findings suggest that there is a stable association of ^99mTc with the Bec-DLPC liposomes and that inhaled liposomes were cleared slowly from the lungs of normal volunteers. The smaller particles produced by the Aerotech II nebulizer are presumably responsible for the somewhat larger deposition and longer persistence of pulmonary activity. These findings encourage further study of this modality of treatment for asthma and related conditions.