植物药金边瑞香对小鼠肠道Peyer’s结的影响

目的：采用环磷酰胺所致小鼠肠道黏膜相关淋巴组织损伤模型。观察植物药金边瑞香浸膏对小鼠肠道Peyer’s结的影响。 方法：实验于2005-01／2005-08在赣南医学院分析实验室完成。44只昆明种小鼠随机分为正常组、金边瑞香组，金边瑞香＋环磷酰胺组及环磷酰胺组4组，每组11只，给予正常组小鼠生理盐水灌胃，每天1次，每次0．02mL／g。连续7d；环磷酰胺组小鼠第7天1次腹腔注射100mg／kg环磷酰胺，其他同正常组；金边瑞香组用金边瑞香浸膏（浓度400g／L，由江西省中医药研究院提供，含生药量5g／mL，临用时用蒸馏水稀释至所需浓度，批号：050310）灌胃，每天1次，每次0．02mL／g，连续7d；金边瑞香＋环磷酰胺组，方法同金边瑞香组和环磷酰胺组。第8天麻醉下脱颈椎处死全部动物，立即小心取出全小肠，肉眼观察其形态并计数小肠Peyer’s结的数量、随后用生理盐水冲洗肠腔，用针头小心取出Peyer’s结按常规方法制备细胞悬液后计数细胞。观察正常组、金边瑞香组、金边瑞香＋环磷酰胺组及环磷酰胺组4组小鼠Peyer’8结，计数Peyer’8结细胞总数，比较Peyer’8结的数量及细胞数。 结果：①正常组、金边瑞香组、金边瑞香＋环磷酰胺组Peyer’s结的数目及结内细胞总数明显高于环磷酰胺组[（5．818&;#177;1．991）。（7．273&;#177;1．678），（6．364&;#177;1．690）．（3．818&;#177;0．874）：（4．223&;#177;1．197）&;#215;10^9L^-1。（6.658&;#177;3．758）&;#215;10^9L^-1，（6．884&;#177;1．807）&;#215;10^9L^-1。（1．451&;#177;1．024）&;#215;10^9L^-1，F=14．28，9．044，P〈0．05-0．0011。②金边瑞香＋环磷酰胺组、金边瑞香组及正常组之间两两比较Peyer’s结的数目及结内细胞总数差别无统计学意义（P〉0，05）。 结论：金边瑞香可对抗环磷酰胺诱导的小鼠肠道Peyer’s结的损伤，提示金边瑞香可能对肠道黏膜免疫具有改善作用。     

金边瑞香浸膏对小鼠免疫功能影响的量效关系

目的:通过检测小鼠灌服具有抗炎症、抑菌、抗脂质过氧化和抗衰老等作用的中药金边瑞香后的非特异性免疫、体液免疫和细胞免疫功能的变化情况,观察不同剂量金边瑞香对小鼠免疫功能的影响及其量效关系。方法:实验于2004-03/2004-06在江西医学院免疫学教研室完成。选用昆明小鼠60只,随机分为生理盐水对照组和1,2,4,8,16g/(kg·d)金边瑞香浸膏实验组共6组,每组10只,分别灌胃0.02mL/g相应不同剂量药物或生理盐水,连续14d。每鼠腹腔注射10mL/L鸡红细胞悬液1mL,1h后麻醉下颈椎脱臼处死小鼠。取腹腔洗液0.5mL滴片,37℃温育30min,甲醇固定,瑞氏染液染色。计数100个巨噬细胞中吞噬鸡红细胞的巨噬细胞数和吞噬的鸡红细胞总数,计算吞噬百分率和吞噬指数。取胸腺和脾脏称重,并计算胸腺指数和脾脏指数。四甲基偶氮唑蓝比色法测定小鼠脾脏T淋巴细胞对ConA诱导的增殖反应,免疫比浊法测定血清免疫球蛋白的含量。对比各组小鼠的胸腺指数和脾脏指数、刺激指数、吞噬百分率和吞噬指数、血清IgG、IgM、IgA的含量,分析不同剂量金边瑞香对小鼠免疫功能的影响及其量效关系。结果:纳入小鼠60只,最终进入结果分析60只,无脱失值。①金边瑞香1,2,4,8,16g/(kg·d)剂量组的胸腺指数、脾脏指数和血清IgG,IgM,IgA含量与对照组相比差异无显著性(F=1.217,0.840,1.085,1.156,0.363,P>0.05)。②金边瑞香4,8g/(kg·d)剂量组T淋巴细胞增殖刺激指数明显高于对照组(1.55±0.19,1.48±0.09,1.22±0.06,F=6.674,P<0.01)。③金边瑞香4,8g/(kg·d)剂量组的小鼠腹腔巨噬细胞的吞噬百分率和吞噬指数明显高于对照组及1,2,16g/(kg·d)剂量组犤(29.13±14.03)%,(40.68±9.70)%,(12.72±2.61)%,(15.37±4.36)%,(15.18±4.22)%,(20.66±7.19)%,F=14.344,P<0.01;1.62±0.24,1.69±0.18,1.35±0.18,1.38±0.19,1.29±0.14,1.43±0.13,F=6.511,P<0.01犦。结论:金边瑞香具有一定的免疫调节作用。1,2,4,8,16g/(kg·d)剂量金边瑞香浸膏对小鼠的非特异免疫、细胞免疫功能有明显的增强作用,8g/(kg·d)剂量金边瑞香对小鼠的免疫功能增强作用最为有效。     

金边瑞香浸膏对小鼠免疫功能影响的量效关系

目的：通过检测小鼠灌服具有抗炎症、抑菌、抗脂质过氧化和抗衰老等作用的中药金边瑞香后的非特异性免疫、体液免疫和细胞免疫功能的变化情况，观察不同剂量金边瑞香对小鼠免疫功能的影响及其量效关系。 方法：实验于2004—03／2004—06在江西医学院免疫学教研室完成。选用昆明小鼠60只，随机分为生理盐水对照组和1，2，4，8，16g／（kg&#183;d）金边瑞香浸膏实验组共6组，每组10只，分别灌胃0．02mkVg相应不同剂量药物或生理盐水，连续14d。每鼠腹腔注射10mL／L鸡红细胞悬液1mL，1h后麻醉下颈椎脱臼处死小鼠。取腹腔洗液0．5mL滴片，37℃温育30min，甲醇固定，瑞氏染液染色。计数100个巨噬细胞中吞噬鸡红细胞的巨噬细胞数和吞噬的鸡红细胞总数，计算吞噬百分率和吞噬指数。取胸腺和脾脏称重，并计算胸腺指数和脾脏指数。四甲基偶氮唑蓝比色法测定小鼠脾脏T淋巴细胞对ConA诱导的增殖反应，免疫比浊法测定血清免疫球蛋白的含量。对比各组小鼠的胸腺指数和脾脏指数、刺激指数、吞噬百分率和吞噬指数、血清IgG、IgM、IgA的含量，分析不同剂量金边瑞香对小鼠免疫功能的影响及其量效关系。 结果：纳入小鼠60只，最终进入结果分析60只，无脱失值。①金边瑞香1，2，4，8，16g/（kg&#183;d）剂量组的胸腺指数、脾脏指数和血清IgG，IgM，IgA含量与对照组相比差异无显著性（F=1．217，0．840，1．085，1．156，0．363，P〉0．05）。②金边瑞香4，8g/（kg&#183;d）剂量组T淋巴细胞增殖刺激指数明显高于对照组（1．55&#177;0．19．1．48&#177;0．09，1．22&#177;0．06，F=6．674．P〈0．01）。③金边瑞香4，8g/（kg&#183;d）剂量组的小鼠腹腔巨噬细胞的吞噬百分率和吞噬指数明显高于对照组及1，2，16g／（kg&#183;d）剂量组[（29．13&#177;14．03）％，（40．68&#177;9．70）％，（12．72&#177;2．61）％．（15.37&#177;4．36）％．（15．18&#177;4．22）％，（20．66&#177;7．19）％，F=14．344，P〈0．01；1．62&#177;0．24，1．69&#177;0．18．1．35&#177;0．18，1．38&#177;0．19，1．29&#177;0．14，1．43&#177;0．13．F=6．511．P〈0．01]。 结论：金边瑞香具有一定的免疫调节作用。1，2，4，8，16g/（kg&#183;d）剂量金边瑞香浸膏对小鼠的非特异免疫、细胞免疫功能有明显的增强作用，8g／（kg&#183;d）剂量金边瑞香对小鼠的免疫功能增强作用最为有效。     

蛇床子素对小鼠实验性肝损伤的干预效应

背景蛇床子素是一种广泛存在于伞形科植物中的香豆素,本课题组曾报道蛇床子素具有Ca2+拮抗作用和抗炎、抗氧化等作用,另据报道蛇床子素能抑制肝肿瘤等所致血清黄嘌呤氧化酶等升高.目的观察蛇床子素对四氯化碳诱发的小鼠肝损伤模型肝损伤的影响.设计完全随机对照动物实验.单位赣南医学院药理教研室,赣南师范学院体育系.材料选用昆明种小鼠40只,雌雄不拘,体质量为(20±2)g.实验药物蛇床子素为成都龙泉高科天然药业有限公司提供.方法实验于2005-03/07在赣南医学院药理教研室完成.实验小鼠以随机数字表法分成4组,即对照组,四氯化碳模型组,蛇床子素50,100 mg/kg剂量组,每组10只.对照组和模型组分别腹腔注射生理盐水10mL/kg;蛇床子素50mg/kg剂量组小鼠腹腔注射蛇床子素50mg/kg;蛇床子素100 mg/kg剂量组小鼠腹腔注射蛇床子素100 mg/kg.1次/d,连续15 d.末次给药后2 h,正常组腹腔注射容量花生油,其余各组均腹腔注射1 g/L四氯化碳花生油溶液10 mL/kg1次.禁食,自由饮水,16 h后各组小鼠麻醉下断头取血.测定血清谷丙转氨酶、谷草转氨酶活性、肝组织丙二醛含量,并观察肝组织病理变化.主要观察指标各组小鼠血清中谷丙转氨酶、谷草转氨酶活性、肝组织丙二醛含量,并观察肝组织病理变化.结果40只小鼠均进入最后结果分析.①给四氯化碳诱导16 h后,模型组小鼠血清中谷丙转氨酶和谷草转氨酶均高于对照组(P＜0.001).蛇床子素组呈剂量依赖性地抑制四氯化碳所致的谷丙转氨酶的升高,100 mg/kg剂量组显著性抑制四氯化碳所致的谷丙转氨酶的升高(P＜0.05),蛇床子素50,100 mg/kg剂量组均可显著性抑制四氯化碳所致的谷草转氨酶的升高(P＜0.01～0.001).②模型组丙二醛含量的增加(P＜0.05),蛇床子素100 mg/kg剂量组的丙二醛的含量接近对照组,可明显降低四氯化碳肝损伤小鼠肝脏丙二醛含量(P＜0.05),蛇床子素50 mg/kg组虽没有显著性抑制四氯化碳所致的丙二醛含量的升高,但有抑制四氯化碳所致肝损伤丙二醛含量的趋势.③四氯化碳肝损伤模型组肝组织明显损伤,肝细胞浊肿、气球样变性,病变以肝小叶中央静脉周围为重.肝小叶内可见轻度、中度肝细胞点状、碎片状坏死;坏死区内有中、重度淋巴细胞和浆细胞浸润,汇管区内有单核细胞浸润.蛇床子素50,100 mg/kg组也有不同程度的肝细胞破坏、炎性细胞浸润等肝损伤病变,但与模型组比较损伤程度明显减轻,尤其是100 mg/kg剂量组表现更为明显.结论蛇床子素能保护四氯化碳所致小鼠肝损伤,表现为降低血清谷丙转氨酶和谷草转氨酶活力和肝脏丙二醛含量.     

蛇床子素对小鼠实验性肝损伤的干预效应

背景：蛇床子素是一种广泛存在于伞形科植物中的香豆素，本课题组曾报道蛇床子素具有Ca^2＋拮抗作用和抗炎、抗氧化等作用，另据报道蛇床子素能抑制肝肿瘤等所致血清黄嘌呤氧化酶等升高。目的：观察蛇床子素对四氯化碳诱发的小鼠肝损伤模型肝损伤的影响。设计：完全随机对照动物实验。单位：赣南医学院药理教研室，赣南师范学院体育系。材料：选用昆明种小鼠40只，雌雄不拘，体质量为（20&;#177;2）g。实验药物：蛇床子素为成都龙泉高科天然药业有限公司提供。方法：实验于2005-03／07在赣南医学院药理教研室完成。实验小鼠以随机数字表法分成4组，即对照组，四氯化碳模型组，蛇床子素50，100mg／kg剂量组，每组10只。对照组和模型组分别腹腔注射生理盐水10mL／kg；蛇床子素50mg／kg剂量组小鼠腹腔注射蛇床子素50mg／kg；蛇床子素100mg／kg剂量组小鼠腹腔注射蛇床子素100mg／kg。1次／d，连续15d。末次给药后2h，正常组腹腔注射容量花生油，其余各组均腹腔注射1g/L四氯化碳花生油溶液10mL／kg 1次。禁食，自由饮水，16h后各组小鼠麻醉下断头取血。测定血清谷丙转氨酶、谷草转氨酶活性、肝组织丙二醛含量，并观察肝组织病理变化。主要观察指标：各组小鼠血清中谷丙转氨酶、谷草转氨酶活性、肝组织丙二醛含量，并观察肝组织病理变化。结果：40只小鼠均进入最后结果分析。①给四氯化碳诱导16h后，模型组小鼠血清中谷丙转氨酶和谷草转氨酶均高于对照组（P〈0．001）。蛇床子素组呈剂量依赖性地抑制四氯化碳所致的谷丙转氨酶的升高，100mg／kg剂量组显著性抑制四氯化碳所致的谷丙转氨酶的升高（P〈0．05），蛇床子素50，100mg／kg剂量组均可显著性抑制四氯化碳所致的谷草转氨酶的升高（P〈0．01～0．001）。②模型组丙二醛含量的增加（P〈0．05），蛇床子素100mg／kg剂量组的丙二醛的含量接近对照组，可明显降低四氯化碳肝损伤小鼠肝脏丙二醛含量（P〈0．05），蛇床子素50mg／kg组虽没有显著性抑制四氯化碳所致的丙二醛含量的升高，但有抑制四氯化碳所致肝损伤丙二醛含量的趋势。③四氯化碳肝损伤模型组肝组织明显损伤，肝细胞浊肿、气球样变性，病变以肝小叶中央静脉周围为重。肝小叶内可见轻度、中度肝细胞点状、碎片状坏死；坏死区内有中、重度淋巴细胞和浆细胞浸润，汇管区内有单核细胞浸润。蛇床子素50，100mg／kg组也有不同程度的肝细胞破坏、炎性细胞浸润等肝损伤病变，但与模型组比较损伤程度明显减轻，尤其是100mg／kg剂量组表现更为明显。结论：蛇床子素能保护四氯化碳所致小鼠肝损伤，表现为降低血清谷丙转氨酶和谷草转氨酶活力和肝脏丙二醛含量。     

复方丹参注射液对小鼠缺氧耐受性影响的观察

目的：观察复方丹参注射液对小鼠缺氧耐受性的影响。方法：180只小鼠随机均分为对照组（生理盐水组）和试验组（复方丹参注射液组），进行不同状态下缺氧耐受性的对比观察。结果：常压缺氧、兴奋状态、二氧化碳分压升高、亚硝酸钠中毒情况下试验组小鼠对缺氧的耐受性明显优于对照组，差异具有显著性（P〈0．001）；煤气中毒、氰化物中毒情况下试验组小鼠对缺氧的耐受性优于对照组（P〈0．05，P〈0．005）。结论：复方丹参注射液可显著提高小鼠在常压缺氧、兴奋状态、二氧化碳分压升高、亚硝酸钠中毒情况下对缺氧的耐受性，而在煤气中毒、氰化物中毒情况下对小鼠缺氧耐受性的影响不显著。     

淫羊藿提取物对小鼠自发活动和睡眠功能的影响

背景：本草纲目记载小檗科淫羊藿属植物淫羊藿有益精气，坚筋骨，补腰漆，强心力等功能，近年来临床应用及药理作用报道较多。目的：观察在抖笼换能器法，阈上、阈下剂量戊巴比妥钠干预的情况下淫羊藿提取物对外、鼠自发活动和睡眠功能的影响。单位：赣南医学院，数理教研室，分析实验室，药理教研室。材料：健康成年昆明种雄性小鼠110只，清洁级，体质量18～22g。方法：2004-08/09在赣南医学院科研中心实验室完成。①小鼠（n=30）腹腔注射1000g/L的淫羊藿提取物（0．01mL/g），15min后放入吊笼中，稳定3min后记录用药后15s内自发活动波形。②小鼠（n=40）腹腔注射1000g/L的淫羊藿提取物（0.01mL/g），15min后，腹腔注射阈上剂量的戊巴比妥钠（2.5g/L）0.02mL/g，观察小鼠翻正反射消失时间。③小鼠（n=40）腹腔注射1000g/L的淫羊藿提取物（0．0lmL/g，15min后，腹腔注射阈下剂量的戊巴比妥钠（2．5g/L）0．01mL/g，观察小鼠翻正反射消失时间。主要观察指标：小鼠自发活动次数；阈上剂量戊巴比妥钠小鼠睡眠时间；阈下剂量戊巴比妥钠小鼠睡眠时间。结果：实验动物110只，全部进入结果分析。①浓度为0．1mL/10g的淫羊藿提取物具有明显抑制小鼠自发活动，与对照组比较中波、大波出现次数显著减少（7．4&;#177;6．5，47．1&;#177;18．7；t=3．265，P〈0．01）。②浓度为0．01mL/g淫羊藿提取物能显著加速阈上剂量戊巴比妥钠小鼠的入睡时间和延长睡眠时间，与对照组差异显著[（3．9&;#177;2．8），（219．7&;#177;87．2）；（5．8&;#177;2．9），（113．0&;#177;77．4）min；t=2．452，2．501，P〈0．05]。③浓度为0．01mL/g淫羊藿提取物能显著加速阈下剂量戊巴比妥钠的入睡时间和延长睡眠时间，与对照组比较差异显著[（6．6&;#177;5．2），（60．3&;#177;71．7）；0，0min；t=3．275，P〈0．01]，与戊巴比妥钠有协同的中枢抑制作用。结论：淫羊藿提取物具有明显的中枢抑制作用，能明显抑制小鼠自发活动，同时还能明显加快阈上剂量戊巴比妥钠小鼠的入睡时间，同时还可显著延长阈上剂量戊巴比妥钠小鼠的睡眠时间。增强阈下剂量戊巴比妥钠的催眠时间和增加入睡动物数。     

淫羊藿提取物对小鼠自发活动和睡眠功能的影响

背景本草纲目记载小檗科淫羊藿属植物淫羊藿有益精气,坚筋骨,补腰漆,强心力等功能,近年来临床应用及药理作用报道较多.目的观察在抖笼换能器法,阈上、阈下剂量戊巴比妥钠干预的情况下淫羊藿提取物对小鼠自发活动和睡眠功能的影响.单位赣南医学院,数理教研室,分析实验室,药理教研室.材料健康成年昆明种雄性小鼠110只,清洁级,体质量18～22 g.方法2004-08/09在赣南医学院科研中心实验室完成.①小鼠(n=30)腹腔注射1 000 g/L的淫羊藿提取物(0.01 mL/g),15 min后放入吊笼中,稳定3 min后记录用药后15 s内自发活动波形.②小鼠(n=40)腹腔注射1 000 g/L的淫羊藿提取物(0.01 mL/g),15 min后,腹腔注射阈上剂量的戊巴比妥钠(2.5 g/L)0.02 mL/g,观察小鼠翻正反射消失时间.③小鼠(n=40)腹腔注射1 000 g/L的淫羊藿提取物(0.01 mL/g),15 min后,腹腔注射阈下剂量的戊巴比妥钠(2.5 g/L)0.01 mL/g,观察小鼠翻正反射消失时间.主要观察指标小鼠自发活动次数;阈上剂量戊巴比妥钠小鼠睡眠时间;阈下剂量戊巴比妥钠小鼠睡眠时间.结果实验动物110只,全部进入结果分析.①浓度为0.1 mL/10 g的淫羊藿提取物具有明显抑制小鼠自发活动,与对照组比较中波、大波出现次数显著减少(7.4±6.5,47.1±18.7;t=3.265,P＜0.01).②浓度为0.01 mL/g淫羊藿提取物能显著加速阈上剂量戊巴比妥钠小鼠的入睡时间和延长睡眠时间,与对照组差异显著[(3.9±2.8),(219.7±87.2);(5.8±2.9),(113.0±77.4)min;t=2.452,2.501,P＜0.05].③浓度为0.01 mL/g淫羊藿提取物能显著加速阈下剂量戊巴比妥钠的入睡时间和延长睡眠时间,与对照组比较差异显著[(6.6±5.2),(60.3±71.7);0,0 min;t=3.275,P＜0.01],与戊巴比妥钠有协同的中枢抑制作用.结论淫羊藿提取物具有明显的中枢抑制作用,能明显抑制小鼠自发活动,同时还能明显加快阈上剂量戊巴比妥钠小鼠的入睡时间,同时还可显著延长阈上剂量戊巴比妥钠小鼠的睡眠时间.增强阈下剂量戊巴比妥钠的催眠时间和增加入睡动物数.     

盐酸氨溴索对哮喘小鼠气道Muc5ac蛋白分泌的影响

目的：观察盐酸氨溴索对哮喘小鼠气道M uc5ac蛋白表达的影响,探讨盐酸氨溴索与支气管哮喘黏液分泌的关系。方法：制作小鼠哮喘模型,应用免疫组织化学法测定盐酸氨溴索组、哮喘组及正常对照组肺组织M uc5ac蛋白的表达。结果：与哮喘组相比,盐酸氨溴索组M uc5ac蛋白表达减少（P〈0.01）。结论：盐酸氨溴索具有抑制哮喘小鼠气道黏液分泌的作用。     

云南虫草菌粉对小鼠迟发型超敏反应影响的实验研究

目的：研究人工培养云南冬虫夏草菌粉（YNCS）对小鼠由环磷酰胺（CY）诱发的增强和降低的迟发型超敏反应（DTH）的影响。方法：小鼠随机分组,每日以受试药物灌胃,同时通过CY分别诱导增高和降低DTH,观察YNCS对增高和降低DTH的影响。结果：高剂量YNCS对CY所致增高和降低的的DTH反应有促进恢复作用（P〈0.05）。结论：提示YNCS对机体细胞免疫功能具有调节功能。     

Oral delivery of macromolecules using intestinal patches: applications for insulin delivery.

Oral drug delivery, though attractive compared to injections, cannot be utilized for the administration of peptides and proteins due to poor epithelial permeability and proteolytic degradation within the gastrointestinal tract. A novel method is described that utilizes mucoadhesive intestinal patches to deliver therapeutic doses of insulin into systemic circulation. Intestinal patches localize insulin near the mucosa and protect it from proteolytic degradation. In vitro experiments confirmed the secure adhesion of patches to the intestine and the release of insulin from the patches. In vivo experiments performed via jejunal administration showed that intestinal insulin patches with doses in the range of 1-10 U/kg induced dose-dependent hypoglycemia in normal rats with a maximum drop in blood glucose levels of 75% observed at a dose of 10 U/kg. These studies demonstrate that reduction in blood glucose levels comparable to that induced by subcutaneous injections can be achieved via enteral insulin absorption with doses only 2-10-fold higher than subcutaneous doses.     

Effect of interleukin-2 on intestinal P-glycoprotein expression and functionality in mice

P-glycoprotein (Pgp), an active drug transporter expressed in enterocytes, can reduce intestinal absorption of drugs. Until now, interleukin-2 (IL2) has been reported as a Pgp modulator only in vitro. The present study examines the effects in vivo of IL2 after chronic treatment on intestinal Pgp protein expression and activity. This work also describes the effects of IL2 on the oral bioavailability of a Pgp substrate (digoxin) and of a Pgp/CYP3A cosubstrate (saquinavir). Human recombinant interleukin-2 (rIL2), administered to mice at 9 million international units/kg by intraperitoneal route twice daily for 4 days, led to a decrease in intestinal Pgp protein expression evaluated by Western blot with C219 antibody. In an in vitro everted gut sac model, rIL2 pretreatment decreased the Pgp-mediated transport of rhodamine 123 across mouse intestine by 37%. Moreover, rIL2 pretreatment markedly raised the area under the curve of orally administered digoxin from 3.5 +/- 0.5 to 9.7 +/- 1.5 mg min l(-1) as a consequence of the reduction in intestinal Pgp activity. rIL2 treatment increased saquinavir bioavailability from 2.5 to 4.5%, showing that first-pass metabolism is not affected and that Pgp by itself has only a moderate effect on saquinavir oral bioavailability. In conclusion, rIL2 pretreatment reduces intestinal Pgp protein expression and activity in mice. However, the effect of such a treatment on drug bioavailability depends on the extent of their metabolism by CYP3A.     

金边瑞香浸膏对小鼠血清IFN-γ、IL-4、IL-18表达的影响

目的观察金边瑞香（daphne odora var.marginata,DOVM）浸膏对小鼠血清干扰素γ（IFN-γ）、白细胞介素4（IL-4）、白细胞介素18（IL-18）表达的影响。方法选用昆明系小鼠60只,随机分为生理盐水组（对照组）和1、2、4、8、16 g/（kg.d）DOVM浸膏组共6组,每组10只。DOVM浸膏不同浓度组分别灌胃给药0.02 mL/g,1次/d,连续14 d;生理盐水组给予生理盐水灌胃0.02 mL/g,1次/d,连续14 d。常规分离血清后,采用生物素双抗体ELISA夹心法（ABC-ELISA）测定各组小鼠血清IFN-γ、IL-4、IL-18的水平。结果1 g/（kg.d）DOVM浸膏组血清IL-4水平明显高于生理盐水组（P〈0.05）。生理盐水组与DOVM浸膏不同浓度组血清IFN-γ、IL-18水平比较差异均无统计学意义（P均〉0.05）,DOVM浸膏不同浓度组间血清IFN-γ、IL-18水平比较差异也均无统计学意义（P均〉0.05）。结论1 g/（kg.d）DOVM浸膏对小鼠IL-4的表达有一定促进作用。     

Fatal acute intestinal pseudoobstruction in mice.

Here we describe the epizootiology and pathology of spontaneous, fatal acute intestinal pseudoobstruction that occurred in a mouse colony of 1000 breeding pairs, mainly of the C57Bl/6 strain and free from known pathogenic agents. Most of the mice affected were dams in the second week of lactation. At necropsy, segments of the small intestines were distended with fluid contents. Widespread apoptosis of the villus epithelium of the small intestine and superficial epithelial cells of the large intestine, associated with strong expression of active caspase 3, was a distinctive feature. Necrotic enterocytes, mucosal erosions, and acute mucosal inflammation were prominent in some mice, and morphologic signs of toxemia were generally present. No light microscopic neuronal changes were apparent in the gut, and no etiologic agents were identified. These results indicate that sudden activation of apoptosis in the trophically stimulated gut epithelium during peak lactation was instrumental for the fatal outcome of the condition, but the primary cause of the motility dysfunction of the bowel was not established.     

水苏糖对艰难梭菌在小鼠肠道内定植与菌群的影响

目的利用艰难梭菌感染(CDI)小鼠模型,评价水苏糖是否具有抑制小鼠肠道内艰难梭菌定植的作用,并分析其对肠道菌群结构的影响。方法将C57BL/6雌鼠随机分为3组,其中不做任何处理的设定为空白对照组,水苏糖干预组和磷酸盐缓冲液(PBS)模型组在建立CDI小鼠模型后分别连续10 d每日给予水苏糖和PBS灌胃处理。利用荧光定量聚合酶链式反应(PCR)检测感染后第10 d各组小鼠粪便中艰难梭菌的含量,并利用16S rRNA基因测序分析各组小鼠肠道菌群结构的变化。结果水苏糖干预导致CDI小鼠粪便中艰难梭菌含量显著降低。水苏糖干预组小鼠粪便的菌群丰富度显著高于PBS模型组,但没有恢复到空白对照组的水平。在门水平上,水苏糖干预可导致CDI小鼠粪便的拟杆菌门(Bacteroidetes)、厚壁菌门(Firmicutes)的相对丰富度显著增高,变形菌门(Proteobacteria)的相对丰富度显著降低。在种水平上,水苏糖干预导致CDI小鼠粪便中格氏副拟杆菌(Parabacteroides goldsteinii)、汉森氏布氏菌(Blautia hansenii)、多形拟杆菌(Bacteroides thetaiotaomicron)的相对丰度显著增高;Parasutterella excrementihominis、狄氏副拟杆菌(Parabacteroides distasonis)的相对丰度显著降低。结论水苏糖干预可有效降低CDI小鼠肠道内艰难梭菌定植量,增加CDI小鼠肠道微生物丰富度,特异性地改变多形拟杆菌和格氏副拟杆菌等菌种的相对丰度。     

Effect of Klebsiella pneumoniae enterotoxin on intestinal transport in the rat.

The effects on intestinal transport of either a semipurified preparation of enterotoxin elaborated by Klebsiella pneumoniae or similaryly prepared control material were tested by marker perfusion studies in the small intestine of rats. At a concentration of 2 mg/ml, the enterotoxin produced net secretion of water, Na, and Cl in both jejunal and ileal segments; HCO3 transport was not affected. Net secretion was evident within 30 min after intorduction of the toxin and was maximal after 90 min. The addition of 56 mM glucose to the enterotoxin-containing perfusion fluid resulted in reversal of water and Na transport to net absorption in both intestinal segments. The enterotoxin also produced a significant depression of xylose absorption in both the jejunum and ileum but did not affect the absorption of either glucose or L-leucine. Intestinal structure was not altered after perfusion of the toxin but insillation of approximately one-quarter of the total perfusion dose into a ligated jejunal loop for 18 h produced fluid secretion and structural abnormalities. These observations confirm the fact that other species of coliform bacteria in addition to tescherichia coli are capable of elaborating an enterotoxin. Such species commonly contaminate the small intestine of persons with tropical sprue and it is suggested that chronic exposure of the intestinal mucosa to the enterotoxin elaborated by these bacteria may be a factor in the pathogenesis of intestinal abnormalities in thid disorder.     

In vitro release of fentanyl from transdermal patches in gastric and intestinal fluid

Context. Fentanyl patches are intended for transdermal use to treat pain. However, these patches have been abused by ingestion, offering a unique mode of drug delivery with unknown drug release characteristics. Objectives. In vitro fentanyl release from patches in simulated gastric and intestinal fluid was evaluated. Materials and methods. Ten 75 mcg/hr fentanyl transdermal patches (Mylan Pharmaceuticals Inc., Morgantown, WV), simulated gastric fluid without enzymes, and USP simulated intestinal fluid (Ricca Chemical Company, Arlington, TX) were obtained. Each fentanyl patch was placed into either 100 mL of simulated gastric fluid or 100 mL of simulated intestinal fluid. Flasks were agitated at 24 rpm while incubated at 36.8°C. Fluid was sampled at time zero and 5, 15, 30, 60, 120, and 180 min after submersion. Fentanyl was assayed using ultra performance liquid chromatography coupled with tandem mass spectrometry (AIT Laboratories, Indianapolis, IN). Results. An average of 239 mcg and 1,962 mcg of fentanyl was released into gastric fluid and 338 mcg and 3,139 mcg into intestinal fluid in 5 min and 3 h, respectively. An average of 26% and 41% of 7.65 mg of fentanyl contained within the 75 mcg/hr patch was released into gastric and intestinal fluid in 3 h, respectively (p = 0.169, Student's t-test). Discussion. Our results demonstrate fentanyl release within 5 min of submersion. Conclusion. These results help support the potential rapid onset of clinical compromise reported and are relevant to the design of future pharmacokinetic studies of fentanyl release from transdermal patches.     

Effects of clindamycin and metronidazole on the intestinal colonization and translocation of enterococci in mice.

The intestinal colonization and translocation of enterococci was studied in mice treated intramuscularly with metronidazole or clindamycin, with or without oral streptomycin. Treatment with metronidazole resulted in selective elimination of strictly anaerobic cecal bacteria, with a 100-fold increase in the numbers of aerobic and facultative gram-negative bacilli and a 10,000-fold increase in the numbers of aerobic and facultative gram-positive species. Clindamycin had a similar effect on the cecal flora except that the numbers of aerobic and facultative gram-positive bacteria decreased at least 10-fold. The predominating gram-positive species in the cecal flora or metronidazole-treated mice was an enterococcus, but this organism could not be recovered from the ceca of clindamycin-treated mice. Translocating bacteria (primarily gram-negative enteric bacteria) were recovered from the mesenteric lymph nodes of the majority of mice given metronidazole or clindamycin. Gram-positive bacteria were not recovered from the mesenteric lymph nodes of 20 clindamycin-treated mice, whereas 26% of 19 metronidazole-treated mice had translocating enterococci. With addition of streptomycin to the metronidazole and clindamycin regimens, mice treated with metronidazole-streptomycin became colonized predominantly with an enterococcus, and this was the only translocating species recovered from 13% of 23 mice; however, enterococci could not be detected in the ceca of clindamycin-streptomycin-treated mice, and Bacillus spp. were recovered from the mesenteric lymph nodes of 8% of 24 mice, reflecting the composition of the cecal flora. The apparent elimination of enterococci from the ceca of clindamycin and clindamycin-streptomycin-treated mice was inconsistent with the observation that the average (n=6) peak levels of clindamycin in blood and ceca were 25 and 21 microgram/ml, respectively, whereas the in vitro MIC was 128 microgram/ml. However, this apparent in vivo activity of clindamycin against enterococci was not evident in mice given 10(9) oral enterococci; the concentrations of cecal enterococci in both clindamycin-streptomycin- and metronidazole-streptomycin-treated mice were 10(10) to 10(11) enterococci per g, with translocating enterococci recovered from approximately half of these antibiotic-treated mice. Thus antibiotic therapy with metronidazole, clindamycin, metronidazole-streptomycin, and clindamycin-streptomycin resulted in a wide variation in the cecal population levels and translocation frequencies of enterococci. This variation appeared to be related to the discrepancy between the in vivo and in vitro activities of clindamycin against enterococci.     

Effect of parenteral antibiotic administration on establishment of intestinal colonization by Candida glabrata in adult mice

We examined the effect of antibiotic treatment on establishment of intestinal colonization by Candida glabrata in adult mice. Subcutaneous ceftriaxone, piperacillin-tazobactam, clindamycin, and metronidazole promoted increased density of stool colonization, whereas cefepime, levofloxacin, and aztreonam did not. These findings suggest that antibiotics that inhibit intestinal anaerobes promote C. glabrata colonization.     

Effect of antibiotic treatment on the intestinal metabolome

The importance of the mammalian intestinal microbiota to human health has been intensely studied over the past few years. It is now clear that the interactions between human hosts and their associated microbial communities need to be characterized in molecular detail if we are to truly understand human physiology. Additionally, the study of such host-microbe interactions is likely to provide us with new strategies to manipulate these complex systems to maintain or restore homeostasis in order to prevent or cure pathological states. Here, we describe the use of high-throughput metabolomics to shed light on the interactions between the intestinal microbiota and the host. We show that antibiotic treatment disrupts intestinal homeostasis and has a profound impact on the intestinal metabolome, affecting the levels of over 87% of all metabolites detected. Many metabolic pathways that are critical for host physiology were affected, including bile acid, eicosanoid, and steroid hormone synthesis. Dissecting the molecular mechanisms involved in the impact of beneficial microbes on some of these pathways will be instrumental in understanding the interplay between the host and its complex resident microbiota and may aid in the design of new therapeutic strategies that target these interactions.