胃泰胶囊的临床药效学研究

目的：研究胃泰胶囊的药理作用。方法：用水杨酸诱发大鼠胃炎模型。用H2清除法及胃内容物重量分别测定正常小鼠胃血流量及胃排空；用二甲苯致小鼠耳肿胀；用皮下棉球致肉芽肿；用醋酸致小鼠扭体反应，胃泰胶囊内含物清膏灌胃给药，结果：胃泰胶囊对水杨酸性胃炎有明显保护作用；增加正常小鼠胃血流及胃排空；抑制二甲苯致小鼠耳肿胀及皮下棉球肉芽增生；抑制醋酸引起的小鼠扭体反应。结论：胃泰胶囊具有抗炎，镇痛，保护胃黏膜，增强胃动力等作用。     

中药提取物甘舒胶囊对小鼠急性酒精中毒的作用及其机制

目的探讨中药提取物甘舒胶囊的解酒功能及有关机制。方法应用二锅头白酒(56°),在雄性昆明种小鼠建立急性酒精中毒动物模型,分别观察甘舒胶囊对小鼠的醉酒时间、醒酒时间。肝组织中的丙二醛(MDA)及还原型谷胱甘肽(GSH)含量的影响。结果甘舒胶囊可显著地延长小鼠的醉酒时间,缩短醒酒时间,并能明显抑制乙醇引起的小鼠肝组织中的MDA含量的增多及对抗乙醇对GSH的抑制作用。结论甘舒胶囊具有显著的解酒作用,此作用可能与其抑制肝组织中的MDA含量及提高GSH水平等的抗氧化作用有关。     

七味红花殊胜丸对实验性肝损伤的保护作用

本研究了七味红花殊胜丸对实验性肝损伤的保护作用。结果表明,七味红花殊胜丸高、中剂量组能显抑制四氯化碳(CCl4)所致慢性肝损伤大鼠血清谷丙转氨酶(ALT)和谷草转氨酶(AST)的升高并提高血清总蛋白含量(TP),减轻肝组织的病理损害程度：高、中剂量能显抑制D-半乳糖胺盐酸盐(D-Gla)所致急性损伤小鼠ALT及肝组织的病理损害程度;各剂量组对小鼠异硫氰酸苯酯(APIT)所致黄胆模型均有非常显的降低血清总胆红素(SB)及ALT作用;高剂量组能明显提高小鼠网状内皮系统吞噬功能。提示七味红花殊胜丸对实验性肝损伤有保护作用,其降酶退黄作用明显。     

黄心胶囊镇咳、祛痰及镇痛作用的研究

目的：观察黄心胶囊镇咳、祛痰及镇痛作用。方法：黄心胶囊对浓氨水所致小鼠及豚鼠咳嗽的影响、对小鼠气管排泌酚红及对大鼠排痰量的影响、对化学、物理刺激所致小鼠疼痛反应的影响。结果：灌服黄心胶囊500、250、125mg／kg能明显减少浓氨水引起小鼠的咳嗽次数，250mg／kg能明显减少浓氨水刺激引起豚鼠的咳嗽次数。灌服250mg／kg具有显著增加气管排泌酚红的作用，而灌服625、500和375mg／kg能显著增加大鼠的排痰量。给小鼠灌服黄心胶囊250、500、625mg／kg能显著地减少醋酸所致的扭体反应次数和提高对热刺激的痛反应阈值。结论：黄心胶囊具有镇咳、祛痰及镇痛的作用。     

湿热安胶囊主要药效学研究

湿热安胶囊是由藿香、半夏、茯苓等组成的纯中药复方制剂,具有芳香化湿、清热和中之功效,临床用于湿热蕴脾证。本研究着重观察了该药对胃肠推进运动的影响、止泻作用、利尿作用及镇痛作用。结果表明,湿热安胶囊可调节小鼠胃肠运动,表现为9g/kg剂量组能明显促进小鼠小肠推进运动(P<0.05),甲基橙法和半固体糊法均表明湿热安胶囊4.5g/kg和2.25g/kg剂量能促进小鼠的胃排空运动(P<0.05),湿热安胶囊4.5g/kg剂量对新斯的明引起的小鼠小肠邮进有显著抑     

APP17肽和救脑益智胶囊水提液对D-半乳糖脑老化小鼠海马PP-1表达的影响

为探讨 APP17肽及救脑益智胶囊水提液对 D-半乳糖脑老化小鼠海马蛋白磷酸酯酶 -1( PP-1)表达的影响。本研究将昆明小鼠随机分为 5组 :正常对照组、D-半乳糖对照组、APP17肽治疗组、小剂量中药治疗组、大剂量中药治疗组 ,每组动物 8只。用 D-半乳糖制备脑老化模型 ,并皮下注射 APP17肽或救脑益智胶囊水提液灌胃对 D-半乳糖脑老化小鼠进行治疗 ,3个月后取脑组织做 PP-1免疫组织化学染色。结果显示 :D-半乳糖小鼠和大剂量救脑益智胶囊水提液治疗组小鼠海马 PP-1阳性细胞数目少 ,染色淡 ;而正常小鼠、APP17肽保护和救脑益智胶囊水提液小剂量治疗的 D-半乳糖小鼠海马阳性反应神经元数目多 ,胞浆与突起深染。结果提示 :抑制凋亡的 PP-1在 D-半乳糖小鼠海马表达降低。 APP17肽和小剂量救脑益智胶囊水提液治疗能影响 D-半乳糖脑病小鼠脑内 PP-1的表达 ,使之接近正常。而大剂量救脑益智胶囊水提液治疗无此作用     

灯盏生脉胶囊对短暂性脑缺血发作小鼠神经保护机制研究

目的建立短暂性脑缺血发作(TIA)小鼠模型,探讨灯盏生脉胶囊(DZSM)对其神经保护作用的机制。方法采用尾静脉注射t-BHP及低氧方法成功制备了TIA样小鼠模型,分别给予不同浓度的DZSM灌胃治疗,ELISA测定血清可溶性P-选择素、TXB2、NO、ET、VEGF含量。结果灯盏生脉胶囊可明显降低模型组小鼠血清P选择素水平和血清TXB2含量;降低模型小鼠的血清ET含量,升高NO;抑制VEGF的过度表达。结论灯盏生脉胶囊通过减轻过氧化物和缺氧造成的血小板激活和释放,抑制局部微血栓形成,改善内皮细胞功能,在促进新生血管形成的同时防止毛细血管通透性的过度增高,发挥对TIA的神经保护作用。     

活化脾细胞免疫诱导同系小鼠低反应性——抑制细胞作用的分析

用ConA活化脾细胞主动免疫同系小鼠,观察了免疫鼠脾细胞在体内外对细胞免疫反应的影响。结果表明,免疫小鼠脾细胞对有丝分裂原以及同种抗原的应答能力比正常小鼠脾细胞弱;它既能抑制抗原非特异性的淋巴细胞转化,又能显著抑制MLR中反应细胞的增生,并且通过过继转输给受者可引起同种移植物存活期延长。提示:免疫小鼠的免疫低反应性形成与体内抑制细胞的诱生有关。     

胆乐胶囊药效及毒性研究

1 胆乐胶囊能有效地抑制饮食致豚鼠体内结石形成,并能明显降低动物体内游离胆红素和胆固醇含量。2 能明显抑制由二甲苯致炎后的小鼠耳肿胀。中和高剂量组其肿胀抑制率均大于50％,并具量效关系。3 对2,4-二硝基酚所致家兔发热具有明显解热作用     

聪灵胶囊对小鼠软脑膜微循环障碍的改善作用

目的 观察聪灵胶囊对小鼠软脑膜微循环障碍的改善作用。方法 将60只小鼠随机分为聪灵胶囊大、中、小剂量组、阳性对照组和正常对照组，分别于灌胃给药10d后，开颅窗观察小鼠软脑膜微循环，然后在软脑膜局部滴加去甲肾上腺素复制微循环障碍模型，观察微循环障碍时小鼠软脑膜微循环。结果 聪灵胶囊各剂量组均可改善去甲肾上腺素所致的小鼠软脑膜局部微循环障碍．使微动脉扩张，血流增快，每视野交织网点数增多，对血流流态也有一定的改善作用，使血色变红。9min后聪灵胶囊各剂量组软脑膜局部微循环障碍基本恢复，而空白对照组恢复不明显。结论 聪灵胶囊能改善小鼠软脑膜微循环。     

美声喉泰含片药效学研究

用小鼠建立咳嗽、炎症、疼痛等模型,观察其咳嗽次数、肿胀程度、毛细血管通透性、扭体次数等试验,结果表明美声喉泰含片对氨水引起的小鼠咳嗽有显著的镇咳作用,对醋酸刺激引起的小鼠腹腔毛细血管通透性增高有显著的抑制作用,对巴豆油引起小鼠耳肿胀有一定抑制作用,对醋酸引起的小鼠疼痛扭体反应有显著的抑制作用。     

Differential effects of antiepileptic drugs and beta-carbolines on seizures induced by excitatory amino acids

Agonists acting at subtypes of glutamate receptors, N-methyl-D-aspartate, kainate and quisqualate, induce convulsions in rodents. Clonic seizures induced in mice by intracerebral administration of N-methyl-D-aspartate, kainate or quisqualate were used to study the anti- and proconvulsant potential of antiepileptic drugs and beta-carbolines. Systemic administration showed that the benzodiazepines clonazepam and midazolam blocked convulsions induced by kainate and had no effect on seizures triggered by N-methyl-D-aspartate and quisqualate. In contrast, diazepam blocked convulsions induced by either excitatory amino acid, as did valproate. The benzodiazepine receptor agonist beta-carboline ZK 93423 blocked convulsions induced by kainate but had no effect on seizures induced by N-methyl-D-aspartate or quisqualate. The antagonist beta-carboline ZK 93426 did not affect convulsions induced by excitatory amino acids, while the inverse agonists FG 7142 and ethyl-beta-carboline-3-carboxylate increased the sensitivity of mice to kainate. Phenobarbital and 2-chloroadenosine protected mice against seizures induced by quisqualate and kainate, while baclofen was active against convulsions produced by kainate. MK-801 selectively blocked convulsions induced by N-methyl-D-aspartate, and enhanced the susceptibility of mice to seizures triggered by kainate and quisqualate. Ethosuximide increased the susceptibility of mice to N-methyl-D-aspartate and had little or no effect on other types of seizures. Diphenylhydantoin enhanced the convulsant potential of quisqualate. Trimethadione and carbamazepine did not affect convulsions induced by N-methyl-D-aspartate, kainate or quisqualate. Intracerebral administration of midazolam protected mice against seizures induced by kainate. Ethosuximide increased the susceptibility of mice to N-methyl-D-aspartate, while diphenylhydantoin to quisqualate convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)     

少年红矾杏平喘糖浆镇咳、祛痰和平喘作用的实验研究

目的:观察少年红矾杏平喘糖浆(简称平喘糖浆)的止咳、祛痰和平喘作用。方法:采用氨水引起小鼠咳嗽实验观察平喘糖浆止咳作用;通过小鼠酚红祛痰实验观察平喘糖浆排痰作用,通过磷酸组胺所致豚鼠哮喘及离体豚鼠气管平滑肌实验观察平喘糖浆平喘作用。结果:平喘糖浆能明显延长引起半数小鼠咳嗽的氨水喷雾时间(EDT50),增加小鼠气管酚红的排出,显著延长豚鼠由磷酸组胺引起哮喘的潜伏期,明显抑制离体气管平滑肌的收缩。结论:平喘糖浆有祛痰、止咳和平喘作用。     

Tumor necrosis factor-alpha is required for gastritis induced by Helicobacter felis infection in mice

Helicobacter pylori colonizes the gastric mucosa of human and causes chronic gastritis. The previous studies have demonstrated that gamma interferon (IFN-gamma) but not tumor necrosis factor-alpha (TNF-alpha) plays a critical role in pathogenesis of gastritis induced by H. pylori infection. In this study we investigated the induction of gastritis induced by H. felis infection in TNF-alpha-deficient mice, comparing with IFN-gamma-deficient mice. The scores of gastritis and epithelial changes of TNF-alpha-deficient mice and IFN-gamma-deficient mice were significantly lower than that of C57BL/6 mice. Moreover, the degrees of gastritis and epithelial changes of TNF-alpha-deficient mice were rather low compared with that of IFN-gamma-deficient mice. In spleen cell cultures stimulated with heat-killed H. felis, IFN-gamma production by TNF-alpha-deficient mice and TNF-alpha production by IFN-gamma-deficient mice were significantly reduced compared with those in C57BL/6 mice. These results suggested that TNF-alpha is involved in pathogenesis of gastritis induced by H. felis infection as IFN-gamma and that an interaction between TNF-alpha and IFN-gamma might be required in pathogenesis of gastritis induced by Helicobacter infection.     

Ovarian morphometrics in TP53‐deficient mice

The objective of these investigations was to characterize ovarian responses to hormonal stimulation in TP53‐deficient mice. TP53‐deficient (KO) and wild‐type (WT) mice were induced to ovulate with pregnant mare serum gonadotropin followed by human chorionic gonadotropin. Effect of estradiol on ovarian morphology was determined in induced and control mice implanted with estradiol‐containing or placebo pellets. Blood was collected and mice were killed 7 days following implantation. Preserved ovaries were serially sectioned and stained. Numbers of follicles (all classifications) decreased with ovulation induction, but did not differ between WT and KO mice. Numbers of corpora lutea (CL) were less in ovulation‐induced KO mice treated with estradiol compared to WT mice. Area of individual CL and serum concentrations of progesterone were greater in ovulation‐induced KO mice given estradiol compared to WT mice. Ovulation‐induced KO mice had more, larger hemorrhagic follicles than similarly treated WT mice, but hemorrhagic follicles were not influenced by estradiol. Proliferation of ovarian surface epithelial cells did not differ between KO and WT mice induced to ovulate and given estradiol. Ovaries from TP53 gene knockout mice (n = 4) induced to ovulate and given a 21‐day estradiol implant three times over 58 days were observed for precursor lesions. There was no indication of precursor lesions in any TP53 KO or WT mouse. TP53 status did not influence recruitment of follicles, but TP53 deficiency hindered the ability of human chorionic gonadotropin to cause ovulation. Anat Rec, 290:59–64, 2007. © 2006 Wiley‐Liss, Inc.     

普鲁卡因酰胺等诱导BALB／c小鼠产生抗核抗体

为了建立药物诱导狼疮（DIL）的动物模型,用普鲁卡因酰胺（Pca)、盐酸肼苯哒嗪（Hyd)和2,2-偶氮-双（3-乙苯基-噻唑啉-6-硫酸）（ABTS）对不同品系小鼠腹腔给药,用ELISA和间接免疫荧光法检测抗核抗体。三种药物都能够诱导小鼠产生抗核抗体,Pca诱导小鼠产生核抗体的阳性率为25%,而Hyd、ABTS诱导的阳性率均为12.5%。Pca、Hyd和ABTS都能诱导BALB/c小鼠而不是C57BL/6小鼠产生抗核抗体,其中DNA特异的抗体主要是IgG,而对组蛋白特异的抗体主要是IgM。结果表明在人体导致DIL的药物Pca、Hyd和ABTS能诱导昆明鼠及BALB/c小鼠产生抗核抗体,提示DIL的发生受遗传背景的影响。     

Blood-stage malaria infection in diabetic mice.

Infection of mice with blood-stage Plasmodium yoelii and P. chabaudi malaria induced hypoglycaemia in normal mice and normalized the hyperglycaemia of mice made moderately diabetic with streptozotocin (STZ). Injection of parasite supernatants induced hypoglycaemia accompanied by hyperinsulinaemia in normal mice, and in STZ-diabetic mice induced a profound drop in blood glucose and restored insulin secretion; however, severely diabetic mice (two injections of STZ) remained hyperglycaemic with no change in insulin levels. We conclude that malaria infection and parasite-derived molecules lower blood glucose concentration, but only in the presence of some residual pancreatic function. Diabetic mice were less anaemic, exerted a significant control of parasitaemia, and showed enhanced phagocytic activity compared with normal mice.     

Toxic effects of recombinant tumor necrosis factor in suckling mice. Comparisons with interferon alpha/beta.

Newborn Swiss and A2G mice were given daily subcutaneous injections for 1 week of highly purified recombinant mouse tumor necrosis factor (TNF) or mouse interferon alpha/beta. Both treatments resulted in inhibition of growth of suckling mice and severe fatty changes and necrosis in the liver. The simultaneous injection of polyclonal antibody to interferon alpha/beta abrogated the effects of interferon but did not block the effects induced by TNF. The kidneys of TNF-treated suckling mice could be distinguished from interferon-treated mice by the absence of glomerular basement membrane abnormalities and the presence of numerous rounded eosinophilic hyaline granules within the cytoplasm of the proximal tubules. Treatment of suckling mice with TNF and interferon alpha/beta induced similar changes in the spleen and thymus. Interferon treatment of suckling A2G mice resulted in the appearance of pulmonary cysts, which were not observed in TNF-treated mice. It is concluded that the pattern of lesions induced in suckling mice by mouse TNF is both similar and different from that induced by mouse interferon alpha/beta.     

Dynamic characteristics and adaptability of reflex eye movements of Fyn-kinase-deficient mice

Fyn-kinase is expressed widely in the entire brain, including the cerebellum. Fyn-kinase-deficient mice are known to exhibit hypersensitivity to ethanol. To evaluate the cerebellar functions of Fyn-kinase, we examined the dynamic characteristics of the horizontal optokinetic response (HOKR) and vestibulo-ocular reflex (HVOR) and its adaptability in Fyn-kinase-deficient mice. The HOKR was induced by sinusoidal oscillation of a checkered screen and the HVOR was induced by sinusoidal oscillation of a turntable in darkness. The HOKR gains of mutant mice were higher than those of the wild-type mice, and the HVOR phases of mutant mice were less advanced than those of the wild-type mice. However, no difference was noted in the adaptability of the HOKR induced by 1 h of sustained screen oscillation between the mutant and wild-type mice. The cerebellar functions appear to be unaffected by Fyn-kinase knockout.     

Effect of Trichinella spiralis infection on passive cutaneous anaphylaxis in mice.

Infection of CFW mice with Trichinella spiralis induced a state of relative unresponsiveness to passive cutaneous anaphylaxis (PCA) induced with hen egg albumin and its corresponding antibodies. The unresponsiveness was to PCA produced either with immunoglobulin G1 (IgG1) or IgE type of antibodies, but was more pronounced with the latter. As few as 25 larvae given by stomach tube 20 days before induced this resistance, although 400 larvae induced a greater resistance. When 400 to 600 larvae were fed to mice, the refractoriness of these mice to PCA was noticed 15 days later. The sera of infected mice had the ability to inhibit mainly PCA induced by IgE. This inhibitory property of sera from infected mice was more pronounced 35 days after infection than 10 months later, when only weak inhibitory activity was detected. Purified rat IgE inhibited the PCA reactions induced in both mice and rats with mouse IgE-type antibody. At high concentrations, evidence of inhibition of the IgG1-induced PCA in mice was also obtained. We believe that the relative unresponsiveness of infected mice is due to an increase in production of IgE which competitively blocks the mast cell sites for other IgE molecules.