玄归滴丸对大鼠急性胃溃疡的保护作用

目的 考察玄归滴丸对乙醇致大鼠急性胃溃疡的保护作用并探讨其作用机制。方法 65只SD大鼠随机分为对照组、模型组、西咪替丁（50 mg/kg）组和玄归滴丸低、中、高剂量（50、100、200 mg/kg,分别为临床等效剂量的2、4、8倍）组。给药组ig给予相应的受试药物,对照组及模型组ig相同剂量的生理盐水,连续7 d,除了对照组外,其余各组均ig无水乙醇制备乙醇型胃溃疡模型。造模1 h后处死大鼠,取胃组织进行大体形态观察,并进行HE染色,光镜下观察病理形态变化;试剂盒法检测胃组织中超氧化物歧化酶（SOD）、丙二醛（MDA）、髓过氧化物酶（MPO）、肿瘤坏死因子-α（TNF-α）、前列腺素E₂（PGE₂）和解痉多肽（SP）含量。结果 玄归滴丸组的胃黏膜损伤程度、病理变化与模型组比较均有不同程度的减轻。与模型组比较,玄归滴丸中剂量组SOD和低、中剂量组MPO水平均显著升高（P<0.05、0.01）;中剂量组MDA水平显著降低（P<0.05）;各剂量组TNF-α水平呈降低趋势;低剂量组PGE₂含量显著升高（P<0.05）;高剂量组SP含量显著降低（P<0.05）。结论 玄归滴丸对乙醇致急性胃溃疡实验大鼠的胃黏膜损伤有较好的保护作用,其作用机制可能与抗氧化、抗炎作用有关。     

闽产三叶青地上部分提取物体内抗炎镇痛作用研究

目的 研究闽产三叶青地上部分提取物体内抗炎镇痛作用。方法 分别采用低、中、高剂量的闽产三叶青地上部分提取物,抗炎作用实验以二甲苯致小鼠耳肿胀急性炎症模型并以醋酸泼尼松为阳性药、角叉菜胶致大鼠足肿胀急性炎症模型并以醋酸地塞米松为阳性药、大鼠棉球肉芽组织增生慢性炎症模型并以醋酸地塞米松为阳性药,镇痛作用实验以化学刺激法（扭体法）及热刺激法（热板法）并以罗通定为阳性药。结果 与模型组比较,闽产三叶青地上部分提取物中、高剂量组及粗提物组对二甲苯所致小鼠耳廓肿胀有明显的抑制作用（依次为P < 0.05,P < 0.01,P < 0.05）,耳肿胀抑制率分别为22.86%,38.79%,20.62%;提取物中、高剂量组及粗提物组对角叉菜胶致大鼠足肿胀急性炎症有明显的抑制作用（P < 0.05或P < 0.01）;提取物低、中、高剂量组及粗提物组均能显著减少大鼠棉球肉芽组织增生慢性炎症模型中大鼠肉芽肿的重量（依次为P < 0.05,P < 0.01,P < 0.01,P < 0.01）,其抑制率分别为28.12%,46.41%,59.58%,44.50%。与模型组比较,在60,90 min,提取物高剂量组能有效提高小鼠的痛阈值延长率（P < 0.05,P < 0.01）,痛阈值延长率最高达65.58%;提取物中、高剂量组及粗提物组能有效抑制醋酸致痛的小鼠扭体次数（依次为P < 0.05,P < 0.01,P < 0.05）,小鼠扭体潜伏期明显延长（依次为P < 0.05,P < 0.01,P < 0.05）,扭体次数明显减少（依次为P < 0.05,P < 0.01,P < 0.05）,镇痛抑制率最高达51.80%。结论 闽产三叶青地上部分提取物具有明显的体内抗炎镇痛作用。     

苯甲酰乌头原碱配伍芍药苷的抗炎镇痛作用研究

目的 探讨不同剂量苯甲酰乌头原碱配伍芍药苷的抗炎镇痛作用。方法 通过小鼠耳肿胀试验、大鼠足肿胀试验、小鼠热板试验和小鼠扭体试验,研究不同剂量苯甲酰乌头原碱配伍芍药苷的抗炎镇痛作用。结果 苯甲酰乌头原碱配伍芍药苷（高剂量配伍组）可显著抑制二甲苯所致的小鼠耳廓肿胀（P<0.05）。在1 h时,苯甲酰乌头原碱配伍芍药苷可显著抑制大鼠足肿胀（P<0.05或<0.01）;在2 h时,中、高剂量配伍组可显著抑制大鼠足肿胀（P<0.05或<0.01）,其中高剂量配伍组相对于芍药苷组和苯甲酰乌头原碱高剂量组,大鼠足肿胀显著减轻（P<0.05）;在4 h时,中、高剂量配伍组可显著抑制大鼠足肿胀（P<0.05或<0.01）,高剂量配伍组相对于芍药苷组,大鼠足肿胀显著减轻（P<0.05）。在1 h和1.5 h时,高剂量配伍组可显著升高小鼠热刺激疼痛的痛阈值（P<0.05）。高剂量配伍组可显著升高小鼠冰醋酸刺激疼痛的痛阈值（P<0.05）。苯甲酰乌头原碱配伍芍药苷可显著减少冰醋酸刺激引起的小鼠扭体次数（P<0.01）,其中高剂量配伍组相对于芍药苷组和苯甲酰乌头原碱高剂量组,小鼠扭体次数显著减少（P<0.01）。结论 苯甲酰乌头原碱配伍芍药苷可增加苯甲酰乌头原碱、芍药苷的抗炎镇痛作用。     

肺咳停颗粒止咳、祛痰、平喘、抗炎作用研究

目的 研究肺咳停颗粒的止咳、祛痰、平喘、抗炎作用。方法 通过浓氨水诱发小鼠咳嗽模型,观察肺咳停颗粒（0.97、1.94、3.88 g生药/kg）止咳作用;通过小鼠酚红分泌实验,观察其祛痰作用;通过卵蛋白诱发豚鼠哮喘模型,观察其（0.59、1.18、2.36 g生药/kg）平喘作用;通过大鼠琼脂肉芽肿炎症模型,观察其（0.67、1.34、2.68 g生药/kg）抗炎作用;通过小鼠二甲苯耳肿胀炎症模型,观察其抗炎作用。结果 与对照组比较,肺咳停颗粒低、中、高剂量组均能延长小鼠咳嗽潜伏期、减少2 min内咳嗽次数;增加小鼠酚红分泌量;延长豚鼠哮喘发作潜伏期;抑制大鼠琼脂块的生长和小鼠耳肿胀程度,并且呈现一定量效关系（P<0.05、0.01）。结论 肺咳停颗粒具有一定的止咳、祛痰、平喘、抗炎作用。     

银马解毒颗粒与肺力咳合剂、桔贝合剂、复方鲜竹沥液祛痰作用比较研究

目的 对比研究银马解毒颗粒与肺力咳合剂、桔贝合剂、复方鲜竹沥液的祛痰作用。方法 实验动物根据体质量分层分组,随机分为对照组,银马解毒颗粒低、中、高剂量（小鼠3.1、6.2、12.4 g/kg,大鼠1.55、3.10、6.20 g/kg,相当于临床成人日等效剂量的0.5、1.0、2.0倍）组,肺力咳合剂（小鼠12 mL/kg,大鼠6 mL/kg）组,桔贝合剂（小鼠8 mL/kg,大鼠4 mL/kg）组,复方鲜竹沥液（小鼠10 mL/kg,大鼠5 mL/kg）组。除银马解毒颗粒组,其余各组均采用临床成人日等效剂量。每组又分为连续给药 3、5、7 d 3个亚组,共计21组,每组10只,雌雄各半。采用小鼠气管段酚红排泌法和大鼠毛细玻管法,通过检测酚红浓度及测量毛细管液柱的长度,考察药物在不同给药时间、不同剂量下的祛痰作用强度和特点。结果 小鼠酚红实验中,与对照组比较,各给药组均能增加气管段酚红排泌量,给药3 d银马解毒颗粒低剂量组无显著差异,其余各给药组具有极显著性差异（P<0.001）;与银马解毒颗粒中剂量组比较,给药7 d时,肺力咳合剂组、桔贝合剂组酚红排泌量显著减少（P<0.05）。大鼠毛细玻管实验中,与对照组比较,各给药组均能增加大鼠排痰量,给药3 d银马解毒颗粒低剂量组和桔贝合剂组无显著性差异,其余各给药组具有显著或极显著性差异（P<0.05、0.001）;与银马解毒颗粒中剂量组比较,给药5 d时,肺力咳合剂组大鼠排痰量增多,差异显著（P<0.05）。银马解毒颗粒祛痰作用随剂量增加和时间延长而增强。结论 银马解毒颗粒与肺力咳合剂、桔贝合剂、复方鲜竹沥液均具有祛痰作用,其中,银马解毒颗粒祛痰作用呈现量-时-效关系。     

复方红景天提取物对大、小鼠脑缺血模型的保护作用

目的 研究复方红景天提取物对小鼠急性脑缺血和大鼠局灶性脑缺血模型的保护作用。方法 昆明小鼠随机分为假手术组、模型组、尼莫地平阳性对照组及复方红景天提取物高、中、低剂量组（2.18,1.09,0.55 g·kg^-1）,灌胃给药7 d后结扎小鼠双侧颈总动脉合并迷走神经制备小鼠急性脑缺血模型,观察小鼠存活时间。SD大鼠随机分为假手术组、模型组、尼莫地平阳性对照组及复方红景天提取物高、中、低剂量组（1.45,0.73,0.36 g·kg^-1）,线栓法制备大鼠大脑中动脉阻塞模型,复制模型前7 d开始灌胃给药,连续给药10 d。测定大鼠神经行为学及脑梗死比例,原位末端标记法检测神经细胞凋亡率,Western bolt检测caspase-3的表达水平。结果 复方红景天提取物高、中剂量组可延长小鼠存活时间,与模型组相比具有显著性差异（P<0.01或P<0.05）。与模型组相比,复方红景天提取物高、中剂量组能显著降低大鼠神经功能评分（P<0.01或P<0.05）,复方红景天提取物各剂量组均能显著降低大鼠脑梗死比例并抑制皮质区神经细胞凋亡,下调caspase-3的表达（P<0.01或P<0.05）。结论 复方红景天提取物对大、小鼠脑缺血模型均具有保护作用,可明显延长急性脑缺血小鼠的存活时间,减轻局灶性脑缺血大鼠的神经功能损伤,缩小梗死灶,抑制神经细胞凋亡,其机制与下调caspase-3的表达有关。     

海马补肾丸免疫调节及抗应激作用的实验研究

目的 采用不同模型评价海马补肾丸免疫调节作用和抗应激作用。方法 健康昆明种小鼠随机分为对照组、模型组、香菇菌多糖（100 mg/kg）组、龟龄集（0.24 g/kg）组和海马补肾丸0.55、1.10、2.20 g/kg组,每天ig给药1次,连续14 d。①采用注射盐酸环磷酰胺致小鼠免疫抑制模型,给药结束尾iv 25%印度墨汁,计算廓清指数（κ）和吞噬指数（α）,观察小鼠肝指数、脾指数和胸腺指数;②采用注射盐酸环磷酰胺致小鼠免疫抑制模型,ip 5%鸡红细胞悬液0.3 mL致敏,观察各组血清溶血素生成量;③给药第8～10天,除对照组外,剩余各组开始ip环磷酰胺80 mg/kg,连续3 d,继续给药,至给药第14天眼眶静脉取血,测定白细胞数及免疫球蛋白IgG、IgM、IgA含量;④SD大鼠随机分为对照组、模型组、单硝酸异山梨酯片20 mg/kg、龟龄集0.12 g/kg和海马补肾丸低、中、高剂量（0.28、0.56、1.12 g/kg）组,每天ig给药1次,连续14 d,观察海马补肾丸对运动疲劳大鼠游泳时间及运动后对血清尿素氮（BUN）、乳酸（LD）、肝糖原水平的影响;⑤健康昆明种小鼠随机分为对照组、模型组、单硝酸异山梨酯片（40 mg/kg）组、龟龄集（0.24 g/kg）组和海马补肾丸低、中、高剂量（0.55、1.1、2.2 g/kg）组,每天ig给药1次,连续5 d,于末次给药后1 h,采用注射异丙肾上腺素致小鼠缺氧模型,将小鼠置于密封瓶中,观察存活时间。结果 与模型组比较,海马补肾丸2.2 g/kg显著增加α及κ（P<0.05、0.01）,海马补肾丸1.1、2.2 g/kg剂量显著增加脾、胸腺系数（P<0.05、0.01）;海马补肾丸各剂量组显著增加血清溶血素生成量（P<0.05、0.01）;海马补肾丸2.2 g/kg剂量组显著增加白细胞数量及免疫球蛋白IgG、IgM、IgA的含量（P<0.05）;海马补肾丸0.56、1.12 g/kg剂量显著延长大鼠力竭游泳时间（P<0.05、0.01）,1.12 g/kg剂量能显著地减少血清中BUN、LD含量,减少肝糖原消耗（P<0.05、0.01）;海马补肾丸1.1、2.2 g/kg剂量能显著延长小鼠缺氧存活时间（P<0.05、0.01）。结论 海马补肾丸具有明显免疫增强和抗应激作用。     

金丝桃苷对急性炎症疼痛模型小鼠的抗炎镇痛作用研究

目的 研究金丝桃苷（Hyp）对急性炎症疼痛模型小鼠的抗炎镇痛作用。方法 昆明种小鼠随机分为对照组,Hyp低、中、高剂量（50、100、200 mg/kg）组及氢化可的松（阳性药,20 mg/kg）组,sc给药,每天给药1次,连续给药5 d后,建立二甲苯所致小鼠耳廓肿胀和醋酸所致小鼠腹腔毛细血管通透性增高的急性炎症模型,观察Hyp对小鼠急性炎症的抗炎作用;阳性药设置为吗啡（1 mg/kg）,其余分组及给药方式同急性炎症实验,连续给药5 d后,建立小鼠醋酸扭体法和热甩尾法模型,观察Hyp对急性疼痛的镇痛作用。结果 100、200 mg/kg的Hyp能够抑制二甲苯所致小鼠耳廓肿胀、降低急性炎症引起的毛细血管通透性增高、减少醋酸扭体次数、提高小鼠热刺激痛阈值,与对照组比较差异显著（P<0.05、0.01）。结论 Hyp对小鼠急性炎症疼痛具有抑制作用。     

伸筋草生物碱对佐剂性关节炎大鼠的抗炎作用及机制研究

目的 探讨伸筋草生物碱对完全弗氏佐剂（CFA）诱导大鼠关节炎的治疗作用及机制。方法 健康SD大鼠48只,随机分为6组,每组8只,即对照组、模型组、依托考昔片（阳性药,1 mg/kg）组及伸筋草生物碱低、中、高剂量（30、60、120 mg/kg）组,除对照组外,其余40只大鼠sc 0.1 mL CFA造模,致炎15 d后,连续ig给药30 d。测定大鼠足趾肿胀率、HE染色后观察造模测踝关节滑膜病理改变;致炎45 d,ELISA法测定血清中白介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）水平。结果 与模型组比较,依托考昔片及伸筋草生物碱低、中、高剂量组足趾肿胀率均显著下降（P<0.05、0.01）;中、高剂量伸筋草生物碱明显改善滑膜细胞、巨噬细胞、纤维细胞增生与炎症细胞浸润;与模型组比较,依托考昔片及伸筋草生物碱高剂量组大鼠血清TNF-α水平显著下降（P<0.05）,依托考昔片及伸筋草生物碱各剂量组IL-1β水平均显著降低（P<0.01）。结论 伸筋草生物碱显著抑制CFA诱导关节炎大鼠关节肿胀,改善大鼠踝关节滑膜病变,其作用机制可能与降低体内IL-1β、TNF-α水平有关。     

芎麻滴丸对血管性认知障碍大鼠社交行为的影响

目的 观察双侧颈总动脉结扎致血管性认知障碍大鼠社交行为的变化,探讨芎麻滴丸对其干预作用。方法 采用永久性结扎双侧颈总动脉法制备血管性认知障碍模型。实验大鼠随机分为假手术组（生理盐水10 mL·kg^-1）,模型组（生理盐水10 mL·kg^-1）,芎麻滴丸高剂量组（生药1.5 g·kg^-1）,芎麻滴丸低剂量组（生药0.75 g·kg^-1）。模型制备第28,42天采用Morris水迷宫对大鼠的学习记忆能力进行测试;模型制备第7,14,28,42天用社交行为仪检测大鼠社交能力的变化。结果 模型制备第7,14天大鼠社交行为无明显变化,模型制备第28天和第42天,模型组大鼠持续接触时间减少（P<0.05）;模型制备第42天,模型组大鼠接触次数减少,逃避潜伏期显著增加,穿越平台次数显著减少（P<0.01）。与模型组大鼠相比,模型制备第28天,芎麻滴丸高剂量组大鼠接触次数显著增加（P<0.05）;芎麻滴丸高、低剂量组大鼠持续接触时间显著增加（P<0.05或<0.01）;模型制备第42天,芎麻滴丸低剂量组大鼠接触次数和持续接触时间增加（P<0.05）,芎麻滴丸高、低剂量组大鼠逃避潜伏期显著减少（P<0.01）。结论 模型制备第42天大鼠出现学习记忆障碍;模型组大鼠第28天大鼠开始出现社交行为障碍,经芎麻滴丸干预后,接触时间和接触次数增加,即可认为其有效缓解由双侧颈总动脉结扎造成的社交能力障碍,且低剂量效果优于高剂量。     

Therapeutic effect of rebamipide in a modified acetic acid-induced buccal mucosal ulcer model

Previous studies have suggested that rebamipide, a gastroprotective drug, might be effective for the treatment of aphthous oral ulcers in Behçet's disease patients. The aim of this study was to confirm the effect of rebamipide on experimentally induced stomatitis in a rat acetic acidinduced oral ulcer model. Buccal mucosal lesions were induced by local injection of 50 l of 99.7% acetic acid into the buccal mucosa, which produced a single large ulcer in each of the treated rats. The ulcer remained up to 14 days. Repeated dose of rebamipide (3-100 mg/kg) dose-dependently decreased the ulcer area. Histopathologically, increased fibrosis and regenerated epithelium were observed in the rebamipide-treated group. In contrast, indomethacin, a cyclooxygenase inhibitor, impaired the healing of ulcers. We have successfully established an improved method for the administration of acetic acid to induce oral ulcers, and rebamipide accelerated the ulcer healing.     

Gastroprotective activity of solidagenone on experimentally-induced gastric lesions in rats

The gastroprotective effect of the labdane diterpene solidagenone was assessed on gastric ulcer in rats. The effect of a single oral dose of the compound was evaluated at 50, 100 and 200 mg kg(-1) in the following test systems: pylorus ligature (Shay), aspirin- and ethanol-induced gastric ulcers. In pylorus-ligated rats (Shay model), the ulcerative index decreased by 37% with solidagenone pre-treatment at the three assayed doses. The effect of a single oral dose of 50 mg kg(-1) solidagenone was comparable with ranitidine at the same concentration and similar to higher doses of the compound. A significant effect (P < 0.001) at 100 and 200 mg kg(-1) was observed in the aspirin-induced ulcer model. At both doses, reduction in the number of lesions was approximately 50% compared with controls. The effect was comparable with the reference compound ranitidine (50 mg kg(-1)). With the ethanol-induced gastric ulcers, the effect of solidagenone at 100 and 200 mg kg(-1) was similar to a single oral dose of 20 mg kg(-1) omeprazole with a 50% reduction of the mean number of lesions compared with controls. In acute toxicity tests on mice, intraperitoneal administration of solidagenone showed no toxicity at doses up to 600 mg kg(-1). This is the first report on the gastroprotective activity of a labdane diterpene.     

Gastroprotective Effect of Oxalis corniculata (Whole Plant) on Experimentally Induced Gastric Ulceration in Wistar Rats

The objective of the present study was to investigate the antiulcer activity of methanol extract of Oxalis corniculata (whole plant) using pylorus ligation and indomethacin-induced gastric ulceration in Wistar rats. The extract was preliminary evaluated for acute oral toxicity test using Organisation for Economic Co-operation and Development guidelines 423. Further, it was studied for antiulcer potential at the dose levels of 125, 250 and 500 mg/kg. Ranitidine was used as a standard drug (100 mg/kg). Acid secretory parameters like gastric volume, pH, total acidity and free acidity were measured in pylorus ligation model, whereas numbers of ulcers, ulcers score and ulcer index was measured in pylorus ligated and indomethacin treated rats. Pretreatment of test extract significantly (p<0.05) decreased the gastric volume, total acidity, free acidity and increase in the pH of the gastric fluid in pylorus-ligated rats. It also showed significant (p<0.05) decrease in number of ulcers, ulcers score and ulcer index in pylorus ligated and indomethacin treated rats. Results of the study suggest that, the methanol extract of Oxalis corniculata possesses significant antisecretory and antiulcer effects and justify the traditional usage of this herb to treat peptic ulcers.     

Improved Lipid Lowering Activity of Bezafibrate Following Continuous Gastrointestinal Administration: Pharmacodynamic Rationale for Sustained Release Preparation of the Drug

Purpose. To evaluate the role of different routes and modes of administration of bezafibrate (BZF) on its hypolipidemic activity. We hypothesize that the major sites of BZF action are located presystemically as in other 'gastrointestinal (GI) drugs.' Thus, continuous administration of the drug to the GI tract is expected to augment its efficacy and provides a rationale for an oral sustained release preparation of the drug. Methods. The hypothesis was investigated in three experimentally induced-hyperlipidemia rat models. Models A and B were based on cholesterol-enriched diets and Model C on induced acute hyperlipidemia by triton 225 mg/kg. The pharmacokinetics and the pharmacodynamics of the drug following various modes of administration were examined. Results. In all cases, continuous administration of the drug into the duodenum (IGI) at a dose of 30 mg/kg/day for 3 days (Models A and B) or over 18 hr (Model C) reduced significantly both total cholesterol and triglycerides levels and elevated HDL cholesterol levels in comparison to bolus oral administration of the same dose, as well as in comparison to equivalent intravenous infusion (Model C). Infusion of the drug directly into the portal vein produced an equivalent activity to IGI administration. The pharmacokinetic study showed 100% oral bioavailability, good colonic absorption properties and an indication for an enterohepatic cycle. Conclusions. The results confirm that BZF has a first pass hepatic pharmacodynamic effect. Administration of BZF in a slow release matrix tablet to the rats produced the same magnitude of effect as IGI administration, thus proving the pharmacodynamic rationale for this mode of administration for GI drugs.     

胃复春胶囊通过抑制AQP3调节炎症性水液代谢障碍改善大鼠急性胃溃疡

目的 通过观察胃复春胶囊对大鼠胃溃疡组织炎症因子和水通道蛋白(aquaporins,AQPs)表达的影响,从水液代谢角度阐释胃复春胶囊对胃溃疡的干预作用,为临床上胃复春胶囊用于胃溃疡的防治提供实验和理论依据。方法 取体质量为190~210 g的雄性SD大鼠40只,按照体质量随机分为假手术组(生理盐水)、模型组(生理盐水)、阳性对照组(雷尼替丁30 mg·kg^-1)和胃复春高、低剂量组(1 000,500 mg·kg^-1)5组。造模前,各组大鼠分别以口服灌胃方式给予相应剂量的药物。连续给药3 d后行乙酸致大鼠胃溃疡模型手术。继续给药5 d后处理大鼠,解剖收集胃液,检测胃液量和胃蛋白酶活性。取胃组织用于大体和病理组织学观察。检测胃组织中超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)和炎症因子的水平,RT-PCR法检测胃组织中AQPs mRNA的表达情况,免疫荧光法检测胃组织中AQP3蛋白的表达情况。分离各组大鼠胃壁细胞,共聚焦显微镜进一步确认胃壁细胞中AQP3的表达水平。结果 胃溃疡模型组大鼠胃溃疡、糜烂明显,伴有出血点;胃复春高、低剂量组大鼠胃黏膜溃疡、糜烂有不同程度的改善。病理组织学可见,模型组黏膜水肿糜烂,炎性细胞浸润,固有层腺体破坏,间质充血等典型胃溃疡症状;胃复春不同剂量组对胃溃疡特征性病变有显著的改善作用。模型组胃蛋白酶活性显著升高,胃复春高、低剂量组和阳性对照组胃蛋白酶活性均下降。此外,胃复春胶囊可显著减低胃溃疡大鼠胃液分泌量,抑制胃蛋白酶活性,提高胃抗氧化酶活性,降低血清炎症因子水平。通过RT-PCR和免疫荧光实验可见,胃复春胶囊对胃溃疡组织AQP3 mRNA和蛋白水平的表达均有显著调控作用,进一步分离胃壁细胞,证实胃复春胶囊对胃壁细胞中的AQP3表达有显著抑制作用。结论 胃复春胶囊能显著改善大鼠胃溃疡症状,提高机体抗氧化水平,调节炎性水液代谢障碍,其作用机制可能与抑制胃壁细胞中AQP3的表达有关。     

Effects of FRG-8813, a new-type histamine H2-receptor antagonist, on the healing of gastric and duodenal ulcer in rats and spontaneously ulcerative mice]

We examined the anti-ulcer effects of FRG-8813, a new-type histamine H2-receptor antagonist, in chronic ulcer models of rats and mice (W/WV). FRG-8813, given orally twice a day for 7 days, accelerated the healing of gastric or duodenal ulcer induced by acetic acid injection or application at the non-antisecretory doses (0.3 approximately 3 mg/kg). Administration of FRG-8813 to rats with ulcers increased the amounts of mucus in the gastric mucosa. These actions of FRG-8813 were more potent than those of famotidine or cimetidine. In W/WV mice, several ulcers spontaneously developed on gastric mucosa during the 8 weeks after the birth. The ulcers were aggravated by several unknown factors after the ulcer generation in W/WV mice. The aggravation of ulcers was inhibited by the 4-week administration of FRG-8813 with diet at the dose of 1 or 10 mg/kg/day, but was not inhibited by cimetidine at the dose of 100 mg/kg/day. From these results, we suggest that FRG-8813 is able to accelerate the healing of ulcers by antisecretory plus increasing actions on the integrity of the gastric mucosal defense mechanisms; therefore FRG-8813 is expected to be a useful drug for the treatment of gastric or duodenal ulcers in humans.     

Protective effect of leaves of Raphinus sativus Linn on experimentally induced gastric ulcers in rats

Raphinus sativus Linn (Cruciferae) commonly known as ‘Radish’ is a multipurpose herb cultivated in different parts of the world for its edible roots and leaves. The present study was aimed to evaluate the antiulcer activity of leaf extracts of R. sativus Linn on acetic acid induced chronic gastric ulcer and pylorus ligation induced gastric ulcer in rats. The acute oral toxicity study revealed that all the extracts were safe up to 2000 mg/kg per oral dose; hence one-tenth of this dose was selected for evaluation of antiulcer activity. In acetic acid induced gastric ulcer models, the ERS, CRS, EARS and AQRS have offered significant protection against acetic acid induced ulcers when compared to control group. While in pylorus ligation induced ulcer model the ERS, EARS and AQRS showed significant protection by decreasing the ulcer index, total acidity and free acidity. In conclusion the leaf extracts of R. sativus Linn are found to possess antiulcer property in the experimental animal models of gastric ulcers, which is consistent with the literature report in the folk medicine.     

The effects of some nonsteroidal anti-inflammatory drugs on experimental induced gastric ulcers in rats

Celecoxib is a frequently used nonsteroidal anti-inflammatory drug (NSAID) in the treatment of rheumatoid arthritis and osteoarthritis. It selectively inhibits cyclooxygenase II (COX-2) enzyme which is responsible for the production of proinflammatory prostanoids. It has been proposed that since it does not significantly inhibit COX-1, an isoenzyme responsible for the production of cytoprotective prostanoids, celecoxib has fewer side effects in the stomach. Dipyrone which is a drug with potent analgesic activity has no significant inhibitory effect on COX. In this sudy, the effects of celecoxib and dipyrone on experimentally induced gastric ulcers in rats were compared with respect to different parameters. In the first experiment, in an attempt to identify the best dose for both drugs, a histamin-induced gastric ulcer model was used and each drug was administered at 5, 25 and 100 mg/kg doses, and ulcer index, acidity and mucus secretion were measured in the stomach. The best dose was determined to be 5 mg/kg for both drugs. Celecoxib was found to delay ulcer healing when compared to dipyrone especially when ulcer index was used as measure. In the second experiment, ulcer index, acidity, mucus secretion, and the levels of myeloperoxidase (MPO), lipid peroxide (MDA), non-protein sulfhydryl groups (NP-SH), and prostaglandin E₂ (PGE₂) were investigated in the stomach of rats with gastric ulcers induced by histamine, stresss and diethyldithiocarbamate (DDC). While celecoxib increased the ulcer index in stress-induced ulcer, dipyrone decreased the index in DDC-induced ulcer. Celecoxib also caused a significant increase of gastric mucus secretion in histamine-induced ulcer model. Gastric lipid peroxidation was significantly increased by dipyrone in the control group without gastric ulcer induction, whereas it was significantly increased by celecoxib in the histamine-induced and stress-induced ulcer groups. Dipyrone promoted a decrease in gastric NP-SH levels in the control group with stress-induced ulcer. With respect to gastric MPO activity, dipyrone caused a decrease in the histamine-induced ulcer group but it caused an increase in the stress-induced and DDC-induced ulcer groups. Gastric PGE₂ levels in the control group without gastric ulcer induction were not affected by celecoxib while they were increased by dipyone. In conclusion, celecoxib prompted the formation of experimentally induced gastric ulcers more than did dipyrone. The study was supported by Osmangazi University Research Funds. Received 8 February 2007; revised 6 March 2007; accepted 13 April 2007     

Gastroprotective activity of α-terpineol in two experimental models of gastric ulcer in rats

BACKGROUND AND THE PURPOSE OF THE STUDY: Several plant essential oils, as well as terpenes present in essential oils, have shown gastroprotective activity. The aim of the present work was to evaluate the gastroprotective activity of α-terpineol, a monoterpene alcohol which is present in essential oils of various plants. METHODS: The gastroprotective activity of α-terpineol was evaluated in rats by assessing the changes in ethanol and indomethacin-induced gastric ulcer scores and on gastric secretory volume and total acidity in pylorus-ligated rats. Alpha-terpineol was administrated orally at the doses of 10, 30, and 50 mg/kg one hour before administration of the ulcer inducing agents by the pylorus ligation procedure. The involvement of endogenous prostaglandins in the protective effect of α-terpineol in ethanol-induced gastric lesions test was assessed by administration of indomethacin (10 mg/kg, s.c.) 30 min before oral administration of α-terpineol at the dose of 50 mg/kg. RESULTS: α-terpineol presented gastroprotective activity against ethanol-induced ulcers at the doses of 10, 30, and 50 mg/kg. Epoxy-carvone at the dose of 10 mg/kg did not present gastroprotective activity against ulcer induced by indomethacin, but at the doses of 30 and 50 mg/kg it attenuated the gastric damages induced by this agent significantly. Pretreatment with indomethacin did not prevent the gastroprotective effect of α-terpineol on ethanol-induced ulcers. Alpha-terpineol also did not affect the gastric secretion in pylorus-ligated rats. MAJOR CONCLUSION: The results suggest that α-terpineol presents gastroprotective action which does not involve either an increase in the synthesis of endogenous prostaglandin or a decrease in the gastric acid secretion.     

氢溴酸樟柳碱注射液大鼠单次和重复给药毒性试验研究

目的 通过SD大鼠的单次和重复静脉给药毒性试验,评价氢溴酸樟柳碱注射液的安全性。方法 单次给药毒性试验采用最大耐受量法,观察大鼠的死亡情况和毒性反应。重复给药毒性试验：将大鼠随机分为溶媒对照组和氢溴酸樟柳碱10、50、200 mg/kg剂量组,每组30只,尾iv给药,连续13周,停药恢复4周。进行各项毒理学指标检测。结果 急性毒性试验：氢溴酸樟柳碱注射液在364.5~504.5 mg/kg对大鼠产生明显毒性,症状有给药时尖叫、俯卧、后肢无力、颤抖、抽搐、惊厥、瞳孔散大、尾部发绀等,甚至造成个别动物死亡。重复给药毒性试验：50、200 mg/kg剂量组出现体质量增长减缓,摄食下降,给药后尖叫,鼻端、眼周异常分泌物增多,皮肤脱毛、结痂,耳廓溃疡、缺损,瞳孔散大,尾部发绀,血红蛋白（HGB）、红细胞压积（HCT）、Cl-浓度升高等症状,200 mg/kg剂量组还出现给药后肌张力减退、颤抖、抽搐、呼吸困难、皮下炎性包块等表现。溶媒对照组和200 mg/kg剂量组动物注射部位均出现静脉炎及静脉周围炎,严重程度无差异,停药4周后病变减轻。结论 氢溴酸樟柳碱注射液SD大鼠静脉单次给药的最大耐受量（MTD）为428.8 mg/kg,约相当于临床剂量的2 573倍;重复给药毒性试验未见明显毒性反应剂量（NOAEL）为10 mg/kg,约相当于临床剂量的60倍。