硝苯吡啶对兔输卵管活动和卵子运行的影响

钙道阻断剂硝苯吡啶(NIF)可明显延缓卵子在兔输卵管内的运行速度。在HCG处理的麻醉兔,NIF抑制输卵管的自发收缩,并说明减弱去甲肾上腺素(NA)和15-甲基PGF_2α所致输卵管腔内压升高和电活动增强。在离体兔输卵管环肌标本,NIF能明显压低NA使峡部和壶腹部环肌张力提高的浓度—反应曲线。以上提示NIF延缓兔卵子运行可能与其阻断钙通道,抑制平滑肌收缩和/或降低输卵管平滑肌对内源性NA和PGF_2α的反应性有关。     

Ghrelin对急性胰腺炎大鼠胃肠动力的影响作用

目的从器官、组织的不同水平测定Ghrelin作用下急性胰腺炎大鼠胃肠动力的变化。方法应用牛磺胆酸钠经胆胰管逆行注射建立急性胰腺炎模型,造模前与造模后6 h分别尾静脉取血2 ml,测定血清淀粉酶、TNF-α、Il-6,再应用Ghrelin对给药组大鼠进行治疗,运用BD2000作为胃肠标记物,同时测定胃残留率和小肠推进比;多导生理仪记录大鼠胃窦肌电活动;多导生理仪记录离体大鼠胃体上1/3起搏区（带有ICC,interstitial cells of cajal的胃肌）和胃窦环行肌肌条收缩波改变。结果各组大鼠造模前与造模后6 h相比血清淀粉酶、TNF-α、Il-6明显升高,给药组大鼠胃残留量较对照组明显减少,给药组胃电慢波振幅及频率显著高于对照组,快波频率也增多,在组织水平,离体的动物胃体起搏区（带有ICC的胃肌）及胃窦环行平滑肌,在Ghre-lin作用下给药组肌条收缩幅度明显高于对照组;给药组胃体起搏区肌条的收缩频率与对照组无明显差别;给药组胃窦环行平滑肌条的收缩频率明显高于对照组,与其在体实验中胃排空明显增强,动力升高相吻合。结论Ghrelin能增强急性胰腺炎大鼠胃肠动力促进胃排空。     

褪黑素对大鼠下丘脑弓状核前阿黑皮素mRNA表达的影响(英文)

目的:观察外源性给予褪黑素对大鼠下丘脑弓状核内神经细胞的前阿黑皮素(POMC) mRNA表达水平的影响。方法:实验大鼠分给药组及对照组,给药组大鼠间隔12 h腹腔注射褪黑素2次(9∶00 am,9∶00pm),每次剂量90mg·kg~(-1),对照组大鼠注射配药液。最后一次注射后12 h,灌注取脑、冰冻切片,进行原位杂交实验,计算机图像处理技术测定染色脑片积分光密度(IOD)值、平均光密度(OD)值。结果:给药组大鼠下丘脑弓状核内POMC mRNA表达明显增强;其IOD和OD值均显著增加。结论:褪黑素可加强大鼠弓状核内POMC mRNA的表达。     

双黄烧伤膏对大鼠烧伤、烫伤的治疗作用研究

目的研究双黄烧伤膏对大鼠实验性烫伤、烧伤感染的治疗作用。方法将大鼠随机分为实验组(双黄烧伤膏组)、阳性对照组(京万红软膏组)、空白对照组。建立大鼠Ⅱ度烫伤模型、Ⅲ度烧伤感染模型,分别涂布给药,单笼饲养,观察并记录创面变化。结果在大鼠烫伤实验中,给药15 d后,各组创面结痂面积明显变小,实验组结痂愈合时间短,与阳性对照组、空白对照组比较,差异有统计学意义(P<0.05、P<0.01);20 d创面面积与阳性对照组相比,差异无统计学意义(P>0.05),与空白对照组相比,差异有统计学意义(P<0.01)。在大鼠烧伤感染试验中,给药9 d后,实验组与阳性对照组相比,差异无统计学意义(P>0.05),与阴性对照组相比,差异有统计学意义(P<0.01)。结论双黄烧伤膏对大鼠实验性烫伤、烧伤感染具有较好的治疗作用。     

三乌胶丸急性毒性的动物实验研究

目的 观察三乌胶丸对美国癌症研究所(ICR)小鼠和SD大鼠的急性毒性反应,以期为三乌胶丸提供安全性评价数据。方法 实验起始时间2020年3—4月。选取ICR小鼠40只及SD大鼠40只,根据中心标准操作规程规定区段随机法将ICR小鼠分为ICR对照组和ICR三乌胶丸组,每组20只;按照区段随机法进行试验设置SD对照组和SD三乌胶丸组,各20只。ICR对照组、ICR三乌胶丸组分别给予纯净水、三乌胶丸40 ml/kg经口灌胃;SD对照组、SD三乌胶丸组分别给予纯净水、三乌胶丸20 ml/kg经口灌胃。各组均连续观察14 d。观察各组一般情况、大体解剖检查结果,给药前及给药后第4、7、10、14天体质量。结果 各组实验动物均未出现死亡,未见明显的活动异常及中毒症状。实验动物各器官表面和切面均未见明显异常。给药前及给药后第4、7、10、14天,2组小鼠及SD大鼠体质量比较,差异均无统计学意义(P>0.05)。结论 三乌胶丸对ICR小鼠在相当于成年人临床给药剂量的264倍(按公斤体质量计)/34倍(按体表面积计)内未见有明显急性毒性反应,三乌胶丸对SD大鼠在相当于成年人临床给药剂量的132倍(...     

己酮可可碱和咯利普兰对淀粉样β蛋白诱导脑损伤后学习记忆功能的影响

目的探讨磷酸二酯酶抑制剂对淀粉样β蛋白(Aβ)诱导的脑损伤大鼠学习记忆功能的改善作用及可能机制。方法SD大鼠分为假手术对照组、模型组、己酮可可碱(PTX)16.5mg.kg-1组和咯利普兰1mg.kg-1组。模型组及给药组大鼠两侧海马内分别注射Aβ25-355μL,术后24h给药组ip给药,每日1次,连续14d。给药7d后进行避暗实验,14d后进行Morris水迷宫实验观察行为学变化。之后处死大鼠,用放射免疫法测定海马组织cAMP含量。结果与模型组比较,PTX组和咯利普兰组大鼠在避暗实验中潜伏期明显延长,在水迷宫实验中寻台时间明显缩短,海马组织cAMP水平显著升高。结论升高脑内cAMP水平可能是磷酸二酯酶抑制剂PTX和咯利普兰增强Aβ脑损伤大鼠学习记忆功能的机制之一。     

中国林蛙卵油的抗焦虑作用

目的研究中国林蛙卵油 (eggoilofRanatemporariachensinensisDavid ,EORTCD)的抗焦虑作用。方法应用高架十字迷路和小鼠爬梯实验评价中国林蛙卵油的抗焦虑活性及其量效、时效关系。结果与对照组比较 ,EORTCD 2 0、4 0 g·kg-1能显著延长大鼠在十字迷路开放通路连续停留时间 ,增加大鼠进入开放通路次数 ,而对封闭通路连续停留时间和进入封闭通路次数无明显影响 ;小鼠爬梯实验中 ,EORTCD 1 4～5 6g·kg-1组小鼠站立数明显减少而爬梯数无显著差异 ;EORTCD抗焦虑时效实验表明在给药后 3 0、60min抗焦虑活性较强 ;γ 氨基丁酸 (γ aminobutyricacid ,GABA) 5 0、1 0 0mg·kg-1分别与EORTCD 1 2 g·kg-1联合给药组的小鼠站立数显著降低而爬梯数无显著减少 ,且比单独给予EORTCD组小鼠站立数少。结论中国林蛙卵油有明显抗焦虑作用。     

温阳振衰颗粒对慢性心衰模型大鼠心肌中MEF2表达的影响

目的:研究温阳振衰颗粒对慢性心衰(CHF)模型大鼠心肌中肌细胞增强子(MEF2)表达的影响。方法:将60只大鼠随机抽取10只作为正常对照组(生理盐水),其余50只大鼠以阿霉素建立CHF模型后随机分为模型对照组(生理盐水)、阳性对照组[依那普利1.8 mg/(kg·d)]和温阳振衰颗粒低、中、高剂量组[0.72、1.44、2.88 g/(kg·d)],每天ig给药2次,连续给药4周。给药结束后,检测各组大鼠心功能指标[左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、左心室收缩末期内径(LVSD)和左心室舒张末期内径(LVDD)],检测各组大鼠心肌中MEF2和磷酸化MEF2(p-MEF2)mRNA及其蛋白的表达。结果:与正常对照组比较,模型对照组和各给药组大鼠LVEF、LVFS明显降低(P<0.05),LVSD、LVDD明显升高(P<0.05);心肌中p-MEF2蛋白表达明显下调(P<0.05),MEF2 mRNA及蛋白表达差异无统计学意义(P>0.05)。与模型对照组比较,各给药组大鼠心功能指标均明显改善(P<0.05);心肌中p-MEF2蛋白表达均明显上调(P<0.05),MEF2 mRNA及蛋白表达差异均无统计学意义(P>0.05)。结论:温阳振衰颗粒能拮抗阿霉素诱导的MEF2蛋白磷酸化的下调作用,这可能是其治疗CHF的机制之一。     

葡萄籽原花青素提取物对大鼠乙酸性结肠炎的保护作用

目的:研究葡萄籽原花青素提取物(GSPE)对大鼠乙酸性结肠炎的治疗作用。方法:制备大鼠乙酸性结肠炎模型,分别设正常对照组、模型对照组、阳性对照组和GSPE低、中、高剂量组,共6组。每天给药1次,共7d。于给药d8时进行大鼠病变结肠大体及组织学评分;用邻联茴香胺法检测结肠组织中MPO活性以考察中性白细胞浸润程度。结果:实验1周时,模型对照组大鼠体重明显下降,结肠湿重明显增加,和模型对照组比较,GSPE低、中剂量组体重下降程度减轻(P<0.05),GSPE高剂量组体重呈增加趋势(P<0.01)。GSPE各剂量组结肠湿重增加幅度较模型对照组明显降低(P<0.05)。大体观察,模型对照组结肠粘膜大面积溃疡、坏死,和模型对照组比较,GSPE各剂量组结肠粘膜溃疡面积缩小,粘膜修复明显。光镜下观察,模型对照组结肠粘膜组织内可见大量炎性渗出物和组织坏死;GSPE各剂量组溃疡面可见多量再生上皮和新生腺体。模型对照组结肠粘膜组织内MPO含量较正常对照组明显升高(P<0.01),GSPE各剂量组MPO活性较模型对照组明显降低(P<0.05)。结论:GSPE对大鼠乙酸性结肠炎有明显的治疗作用,且呈剂量依赖性。     

不同给药方式对P2X_1受体介导大鼠肠系膜动脉收缩反应的影响

目的研究不同方式给予α,β-MeATP对肠系膜动脉P2X1受体介导血管收缩反应的影响。方法制备大鼠离体肠系膜动脉环标本,采用非累积给药法和单浓度给药法两种方式给予α,β-MeATP,记录药物诱发的等长收缩反应。结果两种给药方式给予α,β-MeATP(10-7-10-4mol·L-1)均可使大鼠离体肠系膜动脉产生浓度依赖性收缩反应。以KCl最大收缩反应或以标本湿重标化α,β-MeATP诱发的收缩反应时,α,β-MeATP单浓度给药的收缩反应均大于非累积给药(P<0.01)。以标本湿重标化时,10-4mol·L-1浓度α,β-MeATP诱发的收缩反应分别是(0.73±0.10)g·mg-1(单浓度组)和(0.38±0.05)g·mg-1(非累积组);以KCl最大收缩反应标化时,分别是(53.17±6.0)%(单浓度组)和(36.78±5.71)%(非累积组)。在α,β-MeATP非累积给药组120mmol·L-1KCl诱发的动脉收缩反应小于单浓度给药组和NA对照组(P<0.01)。结论在大鼠肠系膜动脉,非累积给予α,β-MeATP降低P2X1受体介导的收缩反应以及高钾诱发的收缩反应,该给药方式可能导致错误的实验结论 。     

Suppressive Effects of Bay K 8644 on Toxicity of Calcium Channel Blockers in Cultured Rat Embryos

Previous study revealed that calcium channel blockers (CCBs)reduced embryonic heart rates (HRs) and produced morphologicalabnormalities when Gestational Day (GD) 11.5 rat embryos werecultured for 20 hr. The present study was to investigate whethera calcium channel agonist, Bay K 8644 (BAY), prevented CCB-inducedembryotoxicity in vitro. GD 11.5 embryos were exposed to nifedipine(NIF), diltiazem (DIL), and verapamil (VER) either alone orin combination with BAY at 0.1, 1.0, and 10 µg/ml. Thesedoses of BAY alone had no effect on gross morphology. EmbryonicHRs were increased at 10 µg/ml of BAY, but were withincontrol levels at 0.1 and 1.0 µg/ml. The doses of NIF,DIL, and VER were 40, 6.0, and 2.0 µg/ml, respectively,and were the minimum concentrations to produce a 100% effecton morphological abnormalities. Embryonic HRs were reduced to22, 31, and 34% below control levels in the NIF, DIL, and VERgroups, respectively. The negative chronotropic effects of CCBswere inhibited by coadministration with BAY, depending on itsconcentration. When embryos exposed to each CCB were supplementedwith BAY at 1.0 or 10 µg/ml, embryonic HRs were comparableto those of controls. Combined exposures of each CCB and 10µg/mlBAY did not cause any morphological abnormalities. These resultssuggested that mechanisms of CCB embryotoxicity were directlyrelated to pharmacological consequences of calcium channel blockagein developing rats.     

3种基因工程药物对大鼠动脉阻塞性脑损伤治疗作用的比较研究

目的 :探讨基因工程药物NIF、NHH、TNHH对大鼠动脉阻塞性脑损伤的治疗作用。方法 :用线栓法将24只大鼠制成动脉阻塞性脑缺血损伤模型后分为治疗组 (3组 )和模型对照组 ,每组6只。治疗组静脉给予NIF、NHH、TNHH ,模型组给予生理盐水。分别于术后4、8、24、48、72h进行神经行为学评分 ;术后72h取血测定血清APTT ,判断凝血功能 ;取脑组织行TTC染色 ,计算梗塞灶体积 ;HE染色观察脑组织病理变化。结果 :治疗组各时间点行为学评分均优于模型组 (P<0 05) ,血清APTT比模型组均有明显延长 (P<0 05) ,脑组织梗塞灶体积比模型组小 (P<0 05) ,HE染色脑组织病理变化均较模型组轻。结论 :NIF、NHH、TNHH对大鼠动脉阻塞性脑缺血损伤有明显的保护作用 ,其中以TNHH最优。     

ENANTIOSELECTIVE DISTRIBUTION OF VERAPAMIL AND NORVERAPAMIL INTO HUMAN AND RAT ERYTHROCYTES: THE ROLE OF PLASMA PROTEIN BINDING

In this in vitro study, the distribution of the enantiomers of verapamil (VER) and its active metabolite, norverapamil (NOR), into the red blood cells (RBCs) of humans and rats was investigated using a chiral liquid chromatographic assay. When plasma was replaced with buffer, the distribution of VER and NOR enantiomers into both human and rat RBCs was substantial (RBC:blood concentration ratios, 1·39–1·79), non-stereoselective, concentration (125–1000 ng mL⁻¹) linear, and species independent. However, in the presence of plasma, the RBC distribution of VER and NOR was stereoselective, with opposite stereoselectivity for human (S>R) and rat (R>S) blood. Additionally, the presence of plasma caused a reduction in the extent of RBC distribution for both VER and NOR enantiomers and in some cases resulted in nonlinearity in the RBC distribution of the enantiomers. Plasma protein binding studies revealed opposite stereoselectivity in the free fractions in human (S>R) and rat (R>S) plasma for both VER and NOR. These data suggest that the stereoselective protein binding is responsible for the apparent stereoselectivity in the RBC distribution of VER and NOR. The data are also in agreement with the opposite stereoselectivity in the plasma concentrations of VER observed in vivo in rats and humans.     

Photostability determination of commercially available nifedipine oral dosage formulations

Nifedipine (NIF), a 1,4-dihydropyridine calcium channel antagonist, undergoes photodegradation to dehydronifedipine (DNIF) upon exposure to ultraviolet (UV) light and to the nitroso analogue of dehydronifedipine (NDNIF) when exposed to sunlight. NIF photodegradation products do not contribute to clinical activity, thus the content of NIF must remain uniform between equipotent formulations. Large differences in light stability between bioequivalent NIF products could potentially result in the therapeutic failure of unstable preparations. Consequently, if large photostability differences do exist between NIF preparations, product substitution may not be warranted. The light stability of 10 intact immediate- or controlled-release oral NIF formulations, obtained from several European and North American manufacturers, was studied using direct continuous artificial sunlight exposure extending over a 12-week period. The content of both NIF and NDNIF for each product was measured to determine the extent of photodecomposition using a specific and sensitive reversed-phase high pressure liquid chromatographic (HPLC) method. In addition, NIF photodegradation was measured using both pure NIF powder and methanolic NIF solution to determine the effectiveness of the artificial sunlight source used in this study. After 12 weeks of artificial sunlight exposure, less than 3% of NDNIF (w/w initial NIF content) was present in each of the 10 tested dosage forms. Photodegradation was greater than 10% (w/w initial NIF content) in 5–10 min (mean t = 31 min), and in 24 h (mean t = 7.7 days) of artificial sunlight exposure for methanolic NIF solution and pure NIF powder samples, respectively. Therefore, the tested NIF formulations all appear to be photostable up to at least 12 weeks of continuous artificial sunlight exposure, compared with pure NIF powder and methanolic NIF solution. It is concluded that if therapeutic failures or pharmacodynamic differences between the tested NIF formulations were observed, photoinstability as a major contributory factor would be unlikely.     

Characterization of nifedipine solid dispersions

The sublingual administration of nifedipine (NIF) is currently used in clinical practice. The sublingual administration of NIF solid dispersions (SD), by using a suitable dispenser, appears an interesting approach in the treatment of moderate and severe hypertensive emergencies. With this aim nine SD made of NIF and a low viscosity hydroxypropylmethylcellulose (HPMC) in different ratio were prepared by means of spray-drying technique and their structure was studied. Moreover, the drug dissolution properties from SD were verified. The characteristic peaks of crystalline NIF were not detectable by using the X-ray analysis when the NIF/HPMC ratios were lower than 50/50 w/w. In thermograms obtained from SD, the NIF melting endothermic peak disappeared when NIF/HPMC ratios were lower than 30/70 w/w; the experimental Tg values of SD were lower than the Tg values predicted by Gordon Taylor equation suggesting some type of non-ideality of mixing. In the SD FTIR spectra the NH stretching vibrations and the C=O stretch in esteric groups of NIF shift to free NH and C=O regions indicating the rupture of intermolecular hydrogen bond in the crystalline structure of NIF. The prepared SD improved the NIF dissolution rate in comparison with that of commercial NIF or NIF/HPMC physical mixtures. Moreover, the concentration of NIF in the dissolution medium increased decreasing the NIF content.     

联合使用阿斯匹林和硝苯吡啶对冠心病人血浆PGI2、TxA2的影响

将１４０名冠心病人随机分为四组，按规定使用小剂量阿斯匹林及硝苯吡啶，经观察发现：Ｔ＿ｘＢ＿２／ＰＧＦ比值为对照组＞ＡＳＡ组＞ＮｉＦ组＞Ｍ组；用药后ＮｉＦ、Ｍ组ＰＡＷＰ较前明显降低，Ｃｉ、Ｃｏ、Ｆｓ有所增加．结果提示治疗量的ＮｉＦ与小剂量ＡＳＡ合用对ＴｘＡ２／ＰＧＩ２平衡、改善心功能效应最佳。     

Characterization and dissolution behavior of nifedipine and phosphatidylcholine binary systems

Physicochemical properties and the dissolution behavior of binary systems of nifedipine (NIF) and dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylcholine (DMPC) as physical mixtures, solid dispersions and ground mixtures at 9:1 w/w were investigated. The drug and formulations were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy (FTIR) and differential thermal analysis (DTA). The dissolution and solubility of NIF was increased in the order physical mixture < solid dispersion < ground mixture. The powder X-ray diffraction patterns and FTIR spectra indicated absence of major crystalline or molecular changes of NIF or the PCs. The fraction of NIF dissolved after 1 h was approximately 30 and 34% from NIF/DMPC and NIF/DPPC ground mixtures, respectively, and the dissolution was only slightly reduced from NIF/DPPC, 9.75:0.25 w/w systems. The crystal lattice parameter, c, of DPPC and DMPC in the solid dispersion was longer than that of PC alone but each was considered to be in an amorphous state in the ground mixture because of the absence of an X-ray diffraction peak. Full-width at half-maximum (half width) of the X-ray diffraction peak of NIF in the ground mixture was greater than NIF in the physical mixture or solid dispersion, suggesting that the lattice distortion of NIF crystals was increased by grinding. Thermal analysis confirmed the crystalline state of DPPC and DMPC in the physical mixture and the solid dispersion but an amorphous state in the ground mixture. Thus, an increase in lattice distortion of NIF crystals due to grinding and an amorphous state of DPPC or DMPC in the ground mixtures are considered mainly responsible for the larger increase in dissolution rate and extent of dissolution of NIF after 1 h compared to the solid dispersion formulation.     

Comparison of the pharmacokinetics of verapamil in the pregnant and non-pregnant rabbit: study of maternal and foetal tissue levels

1. The comparison of the pharmacokinetics of verapamil (VER) has been studied between the non-pregnant and pregnant rabbit following VER intravenous (i.v.) bolus administration. Also studied has been VER tissue distribution in the non-pregnant and pregnant rabbit and its foetuses following an i.v. infusion of VER. 2. When the pharmacokinetic variables were compared between the pregnant and non-pregnant rabbit, it was observed that t(1/2)lambda2 V1 and V(D) were significantly higher in the non-pregnant than in the pregnant rabbit. Moreover, lambda(z) was significantly lower in the non-pregnant than in the pregnant rabbit. However, AUC and CL showed no significant differences between the pregnant and non-pregnant rabbit. 3. When tissue concentrations were examined, it was found that in most of the tissues studied high concentrations of VER were found both in the pregnant and non-pregnant rabbit. Furthermore, VER concentrations in the uterus, heart, spleen and kidney were significantly higher in the non-pregnant than in the pregnant rabbit. 4. The results suggest that VER diffuses poorly through the placenta, given that VER blood concentrations were lower in blood foetuses than in maternal blood. Moreover, the concentrations of VER in the selected foetal tissues were either similar (brain and liver) or lower than those observed in maternal tissues.     

Physical properties and solubility studies of Nifedipine-PEG 1450/HPMCAS-HF solid dispersions

Low-order high-energy nifedipine (NIF) solid dispersions (SDs) were generated by melt solvent amorphization with polyethylene glycol (PEG) 1450 and hypromellose acetate succinate (HPMCAS-HF) to increase NIF solubility while achieving acceptable physical stability. HPMCAS-HF was used as a crystallization inhibitor. Individual formulation components, their physical mixtures (PMs), and SDs were characterized by differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy (FTIR). NIF solubility and percent crystallinity (PC) were determined at the initial time and after 5?days stored at 25?°C and 60% RH. FTIR indicated that hydrogen bonding was involved with the amorphization process. FTIR showed that NIF:HPMCAS-HF intermolecular interactions were weaker than NIF:PEG 1450 interactions. NIF:PEG 1450 SD solubilities were significantly higher than their PM counterparts (p?<?0.0001). The solubilities of NIF:PEG 1450:HPMCAS-HF SDs were significantly higher than their corresponding NIF:PEG 1450 SDs (p?<?0.0001-0.043). All the SD solubilities showed a statistically significant decrease (p?<?0.0001) after storage for 5 days. SDs PC were statistically lower than their comparable PMs (p?<?0.0001). The PCs of SDs with HPMCAS-HF were significantly lower than SDs not containing only PEG 1450. All SDs exhibited a significant increase in PC (p?<?0.0001–0.0089) on storage. Thermogravimetric analysis results showed that HPMCAS-HF bound water at higher temperatures than PEG 1450 (p?<?0.0001–0.0039). HPMCAS-HF slowed the crystallization process of SDs, although it did not completely inhibit NIF crystal growth.