小儿健脾膏整方及其拆方对豚鼠离体胃肌、回肠平滑肌的作用比较

目的 观察比较小儿健脾膏整方及其拆方对豚鼠离体胃、回肠平滑肌的作用,进一步辨识方中促胃肠动力药效物质及其与整方的关系。方法 运用生物信号采集系统记录小儿健脾膏整方及其拆方对正常豚鼠离体胃、回肠平滑肌收缩张力的影响。结果 整方能显著促进胃、回肠平滑肌收缩。拆方中丁香、吴茱萸和山楂对胃肌收缩有促进作用,肉桂、白胡椒作用不显著。丁香和山楂对回肠平滑肌收缩有促进作用,且丁香 > 山楂 > 整方,吴茱萸则呈抑制作用,肉桂、白胡椒作用不显著。两两药物配伍对胃肌收缩有促进作用的组合为：丁香+肉桂、丁香+白胡椒、吴茱萸+肉桂、吴茱萸+白胡椒、山楂+肉桂。对回肠平滑肌收缩有促进作用的组合为：丁香+肉桂、丁香+白胡椒、山楂+肉桂;而吴茱萸+肉桂组、吴茱萸+白胡椒组则呈显著抑制作用。结论 小儿健脾膏整方能显著促进豚鼠胃、回肠平滑肌收缩,其中,丁香和山楂为主要促胃肠动力单味药。     

小儿健脾膏促胃肠动力作用研究

目的 观察小儿健脾膏对离体豚鼠回肠和大鼠胃肌收缩、在体大鼠胃肌收缩及整体小鼠胃排空与肠推进的影响。方法 离体和在体实验中,运用生物机能实验系统检测小儿健脾膏对回肠和胃肌收缩张力的影响;整体实验中,运用称重法和标记法测定小鼠胃排空率与肠推进比率。结果 离体实验中,不同剂量的小儿健脾膏均可增大豚鼠回肠和大鼠胃肌的平均收缩幅度;在体实验中,中、高剂量小儿健脾膏可显著增加大鼠胃肌的平均收缩幅度,且高剂量对大鼠胃肌的收缩与新斯的明具有协同作用;整体实验中,不同剂量的小儿健脾膏均能显著加速阿托品所致胃肠动力障碍模型小鼠的胃排空与肠推进。结论 小儿健脾膏具有促进胃肠动力的药理作用。     

基于路径分析数学模型探讨逍遥散功效药队抗抑郁配伍关系

目的 采用路径分析数学模型定量表征逍遥散功效药队（健脾药队、疏肝药队）对整方抗抑郁药效的贡献。方法 大鼠适应性饲养1周后,基于行为学数据以及体质量,随机分为对照组、模型组、疏肝（25 g·kg^-1,柴胡、薄荷、白芍、当归）组、健脾（21.3 g·kg^-1,白术、茯苓、生姜、甘草）组、逍遥散（46.3 g·kg^-1,柴胡、当归、白芍、白术、茯苓、甘草、薄荷、生姜质量比为6∶6∶6∶6∶6∶3∶2∶2）组,制备慢性温和不可预知应激（CUMS）抑郁大鼠模型同时给药。对照组和模型组给予等量生理盐水,在给药1 h后开始造模,每天给药1次,持续28 d。在第0、1、2、3、4周分别对所有动物进行称体质量、糖水偏爱实验;在造模结束后对大鼠进行强迫游泳和水迷宫行为学测试。应用IBM SPSS Statistics 26软件,处理、分析行为学数据,并绘制路径分析效果图。结果 造模第4周,模型组大鼠体质量、糖水偏爱率、水迷宫穿越平台次数显著低于对照组（P＜0.05）,强迫游泳不动时间显著高于对照组（P＜0.05）。与模型组比较,各给药组体质量、穿越平台次数显著增加（P＜0.05、0.01） ,其中逍遥散组效果最优,健脾组效果次之,最后为疏肝组;各给药组糖水偏爱率显著增加（P＜ 0.01） ,逍遥散的作用优于健脾组和疏肝组,与对照组最为接近;各给药组不动时间显著减少（P＜ 0.05、0.01）,健脾的效果优于逍遥散和疏肝组。路径分析结果显示,体质量：疏肝药队对整方的作用是促进作用,但健脾药队具有抑制作用,疏肝药队的正向作用强于健脾药队的抑制作用;水迷宫实验：疏肝药队和健脾药队均发挥正向促进作用;糖水偏爱率：健脾药队对整方的贡献是正向促进作用,但疏肝药队是抑制作用,健脾药队的正向促进作用强于疏肝药队的抑制作用;强迫游泳：健脾药队的作用是正向促进的,但疏肝药队是抑制作用,疏肝的抑制作用强于健脾的正向作用。结论 与疏肝药队相比,健脾药队能更好地改善抑郁症行为学指标;路径分析模型可直观反映各药队抗抑郁作用的强弱,又能定量表征各药队对整方抗抑郁作用的贡献。     

吴茱萸碱对大鼠离体子宫平滑肌的舒张作用及机制研究

摘 要 目的：探讨吴茱萸碱对大鼠离体子宫平滑肌的舒张作用及其可能机制。方法: 以前列腺素F2α（PGF2α）诱导大鼠离体子宫平滑肌收缩,生物机能实验系统观察吴茱萸碱舒张离体子宫平滑肌的作用以及辣椒素受体阻断药capsazepine、磷脂酶Cβ阻断药U73122和钙调蛋白阻断药W 7对吴茱萸碱作用的影响,Prism 5.01非线型可变斜率回归计算半效浓度(EC50)。结果: 吴茱萸碱对PGF2α(EC50=9.60×10-11 mol·L^-1)收缩离体子宫平滑肌舒张作用的EC50为9.56×10 9 mol·L^-1。半抑制浓度(IC50)的capsazepine(6.30×10-11 mol·L^-1),U73122(2.57×10-11 mol·L^-1)和W 7(5.65×10-13 mol·L^-1)预舒张离体子宫平滑肌后,吴茱萸碱的EC50降低,量效曲线左移。EC50的大小顺序依次为：U73122 吴茱萸碱(1.95×10-12 mol·L^-1)＞capsazepine 吴茱萸碱(7.35×10-13 mol·L^-1)＞W 7 吴茱萸碱(8.88×10-15mol·L^-1)。结论: 吴茱萸碱对PGF2α收缩的离体子宫平滑肌有舒张作用,其作用机制可能与辣椒素受体1、磷脂酶Cβ和钙调蛋白有关。     

小儿健脾膏外治功能性再发性腹痛疗效观察

目的 观察小儿健脾膏外治功能性再发性腹痛的疗效。方法 将120例功能性再发性腹痛患儿分为2组（治疗组和对照组）,各60例,治疗组穴位贴敷小儿健脾膏,对照组口服654-2片和双歧杆菌三联活菌散。比较2组腹痛缓解和消失情况。结果 治疗组疗效优于对照组,2组腹痛消失率、腹痛缓解和消失时间有显著性差异（P<0.05）。结论 小儿健脾膏穴位贴敷治疗功能性再发性腹痛疗效肯定,操作简单方便,患儿依从性好。     

窍门评说

正风湿性关节炎外治法肉桂、干姜、白胡椒、细辛各100克,公丁香50克,研末,用200克蜂蜜,熬成膏,摊在纱布上,从初伏第十天开始贴患处,到三伏末时除去。广西石先生点评:读者所荐方中,肉桂性辛温,有温中散寒、行淤消肿、活血止痛之功效;干姜为生姜晒干所得,辛辣温散,有辛散风邪、清除寒痛之功效;白胡椒有温散寒湿、行气止痛之功效;细辛辛香温燥,有祛散风寒、解痉止痛功效;公丁香性味温香,有祛风散寒、行气止痛作用;蜂蜜     

小儿止泻膏对幼龄大鼠慢性腹泻的治疗作用及机制研究

目的采用幼龄大鼠慢性腹泻模型,评价小儿止泻膏的止泻作用,并探讨其作用机制。方法采用ig番泻叶制备幼龄大鼠慢性腹泻模型,给予蒙脱石散1.62 g/kg和小儿止泻膏低、中、高剂量（2.03、4.05、8.10 g/kg）进行治疗,给药1、3 d,分别测定稀便率、稀便级、腹泻指数;给药第4天,测定小肠含水量并取血,比色法测定血清中琥珀酸脱氢酶（SDH）、淀粉酶活力、D-木糖,酶联免疫法测定血清D-乳酸、白介素-1β（IL-1β）及肿瘤坏死因子-α（TNF-α）水平。结果给药1次,小儿止泻膏4.05、8.10 g/kg剂量组均可明显降低稀便率,8.10 g/kg剂量组明显降低腹泻指数;给药3次,小儿止泻膏2.03、4.05、8.10 g/kg剂量组均能明显降低稀便率,4.05、8.10 g/kg剂量组明显降低腹泻指数,降低血清D-乳酸水平,8.10 g/kg剂量组能明显升高血清D-木糖水平。小儿止泻膏对SDH、淀粉酶活力及IL-1β、TNF-α水平均无明显影响。结论小儿止泻膏对幼龄大鼠慢性腹泻有明显的治疗作用,主要作用机制是改善肠道的吸收功能及通透性。     

罗氟司特和齐留通对哮喘大鼠气道平滑肌收缩功能的影响

目的 通过观察磷酸二酯酶4抑制剂罗氟司特和5-脂氧酶抑制剂齐留通对哮喘气道平滑肌收缩功能的影响,探讨罗氟司特和齐留通对气道平滑肌的药理作用。方法 取正常及哮喘大鼠的气道平滑肌条,采用乙酰胆碱（acetylcholine,Ach）梯度累积给药进行肌条收缩功能研究,并进行罗氟司特或齐留通梯度累积给药的肌条舒张功能研究,同时设置药物预孵处理,利用张力换能器和计算机生物信号采集系统观察和记录各种方式处理下其收缩功能的变化。结果 采用累积剂量给药法加入收缩剂Ach（10^-8~10^-3 mol·L^-1）后,正常大鼠和哮喘模型大鼠气道平滑肌收缩无显著性差异。由Ach诱发平滑肌条收缩达到最大程度,采用累积剂量给药法加入罗氟司特或齐留通（10^-8~10^-3 mol·L^-1）后,哮喘大鼠气道平滑肌对罗氟司特的敏感性高于正常大鼠,而对齐留通的敏感性低于正常大鼠。使用罗氟司特预孵,并采用累积给药法加入收缩剂Ach（10^-8~10^-3 mol·L^-1）,哮喘大鼠气道平滑肌和正常大鼠对Ach的反应性无明显差异,而齐留通预孵后,累积给药法加入Ach（10^-8~10^-3 mol·L^-1）,哮喘大鼠平滑肌对Ach的反应性明显高于正常健康大鼠。结论 罗氟司特能抑制哮喘气道平滑肌的收缩功能,同时不诱导气道的高反应性,而齐留通对哮喘气道平滑肌的收缩抑制作用不明显,且可能诱导气道高反应性。     

升陷汤及各单味药对阿霉素致心肌细胞损伤的保护作用

目的 研究升陷汤（SXT）及各单味药对阿霉素致心肌细胞损伤的保护作用。方法 将乳鼠缺氧/复氧培养的心肌细胞分为正常对照组（Con组）、阿霉素诱导损伤组（M组）和不同药物（升陷汤及其各单味药）治疗阿霉素诱导损伤组（SXT、A-E组）。检测指标包括细胞活力、细胞活性氧族（ROS）、Ca²⁺和乳酸脱氢酶（LDH）水平。结果 与正常组相比,阿霉素能够造成心肌细胞损伤,与模型组比较,升陷汤全方以及各单味药实验组均能增强细胞的活力,降低细胞Ca²⁺和LDH浓度;除桔梗和升麻外,升陷汤全方及其他单味药能够降低ROS的浓度,实验结果提示,在早期阿霉素治疗中如果应用升陷汤,一定程度上能降低阿霉素的心脏毒性作用。结论 升陷汤及各单味药对阿霉素致心肌细胞损伤具有保护作用。     

温通巴布膏对腹泻模型鼠血清前炎症介质水平的影响

<正>温通巴布膏主要由丁香、肉桂、小茴香等药制成,其全方及各味药均具有抗炎、抗腹泻作用。本试验通过建立小鼠腹泻模型,研究其对腹泻模型鼠的血清前炎症介质水平的影响,为温通巴布膏的临床应用提供科学资料。     

小儿健脾膏外治小儿厌食证的疗效评价

目的　观察小儿健脾膏改善小儿厌食的作用,并进行疗效评价。方法：将192例小儿厌食患儿分为2组,对照组86例,给予小儿消食颗粒口服,治疗组106例小儿健脾膏穴位贴敷治疗。比较两组疗效及不良反应。结果：治疗组疗效优于对照组,两组治愈率、总有效率有显著性差异 ( P＜0.05 ),食欲食量改善起效时间无明显差异,但小儿健脾膏较小儿消食颗粒疗效更持久,不易反复。结论：小儿健脾膏具有改善小儿厌食促进消化的作用,且安全、方便、起效快、持久,易于儿童接受。     

小儿健脾开胃合剂联合赖氨酸维B12颗粒治疗小儿厌食症的临床研究

目的研究小儿健脾开胃合剂联合赖氨酸维B_(12)颗粒治疗小儿厌食症的临床疗效。方法选取2017年12月—2018年12月青海省妇女儿童医院收治的80例厌食症患儿为研究对象,将所有患儿随机分为对照组和治疗组,每组各40例。对照组患儿口服赖氨酸维B_(12)颗粒,1～5岁,0.5袋/次,2次/d,6～12岁,1袋/次,2次/d;治疗组患儿在对照组治疗的基础上口服小儿健脾开胃合剂,10 mL/次,2次/d。两组患儿持续治疗30 d。观察两组的临床疗效,比较两组的微量元素、生化指标水平。结果治疗后,对照组和治疗组的总有效率分别为82.50%、95.00%,两组比较差异有统计学意义(P0.05)。治疗后,两组患儿铁、钙和锌水平均显著升高,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组患儿铁、钙和锌水平均明显高于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患儿血红蛋白(Hb)、血清淀粉酶(AMS)、血清铁蛋白(SF)水平均显著升高,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组患儿Hb、AMS、SF水平明显高于对照组,两组比较差异有统计学意义(P0.05)。结论小儿健脾开胃合剂联合赖氨酸维B_(12)颗粒治疗小儿厌食症具有较好的临床疗效,能改善患儿贫血症状,调节血清微量元素水平,具有一定的临床推广应用价值。     

Water extracts of cinnamon and clove exhibits potent inhibition of protein glycation and anti-atherosclerotic activity in vitro and in vivo hypolipidemic activity in zebrafish

Advanced glycation end products contribute to the pathogenesis of diabetic complications and atherosclerosis. Aqueous extracts of ground pepper, cinnamon, rosemary, ginger, and clove were analyzed and tested for anti-atherosclerotic activity in vitro and in vivo using hypercholesterolemic zebrafish. Cinnamon and clove extracts (at final 10 μg/mL) had the strongest anti-glycation and antioxidant activity in this study. Cinnamon and clove had the strongest inhibition of activity against copper-mediated low-density lipoprotein (LDL) oxidation and LDL phagocytosis by macrophages. Cinnamon or clove extracts had potent cholesteryl ester transfer protein (CETP) inhibitory activity in a concentration-dependent manner. They exhibited hypolipidemic activity in a hypercholesterolemic zebrafish model; the clove extract-treated group had a 68% and 80% decrease in serum cholesterol and TG levels, respectively. The clove extract-fed group had the smallest increase in body weight and height and the strongest antioxidant activity following a 5-week high cholesterol diet.Hydrophilic ingredients of cinnamon and clove showed potent activities to suppress the incidence of atherosclerosis and diabetes via strong antioxidant potential, prevention of apoA-I glycation and LDL-phagocytosis, inhibition of CETP, and hypolipidemic activity. These results suggest the potential to develop a new functional dietary agent to treat chronic metabolic diseases, such as hyperlipidemia and diabetes.     

Enantioselective Synthesis and Pharmacological Evaluation of a New Type of Verapamil Analog with Hypotensive and Calcium Antagonist Activities

Purpose. The syntheses and evaluation for cardiovascular activity in the rat of both enantiomers of a verapamil analog in which the cyano group has been replaced by hydroxyl. Methods. ( + )- and (–)--[3-[[2-(3,4-Dimethoxyphenyl)ethyl]methylamino]propyl]-3, 4-dimethoxy--(l-methyl ethyl)benzyl alcohol were prepared from chiral sulfoxides produced by microbial biotransformations using Mortierella isabellina ATCC 42613 or Helminthsporium species NRRL 4671, and were examined for hypotensive and calcium antagonist activity using anaesthetized normotensive rats and isolated rat aorta and atria. Results. The analogs showed a pharmacological profile similar to that exhibited by verapamil, possessing a remarkable hypotensive activity, accompanied by a significant bradycardia, in anaesthetized normotensive rats. In vitro, these analogs displayed clear inhibitory effects: in isolated rat aorta they inhibited, in a concentration-dependent fashion, the contractions and ⁴⁵Ca²⁺ uptake induced by norepinephrine and high KC1, and in isolated rat atria the analogs considerably decreased the rate of contraction (negative chronotropic effects). No significant differences between the quantitative cardiovascular effects produced by the two enantiomers of the verapamil analogs were observed. Conclusions. The results suggest that, like that of verapamil, the cardiovascular activity exhibited by the new compounds seems to be due, at least in part, to a blockage of transmembrane calcium channels present in vascular smooth muscle cells.     

Effects of Weichang'an Pill on contraction of isolated ileum smooth muscles in rats北大核心CSCD

目的研究胃肠安丸(Weichang′an pill,WCA)、胃肠安丸醇提物(Ethanol extract of Weichang′an pill,EE)、胃肠安丸水提物(Water extract of Weichang′an pill,WE)及其活性成分对乙酰胆碱(Acetylcholine,ACh)诱导的大鼠离体回肠平滑肌收缩的影响及机制。方法采用离体组织浴实验,在ACh的作用下,加入WCA、EE、WE或其活性成分,记录离体大鼠回肠平滑肌的收缩张力;通过分子对接的方法探究活性成分与毒蕈碱型乙酰胆碱M3受体的结合亲和力。结果WCA、EE、WE均可明显抑制ACh诱导的回肠平滑肌兴奋性收缩。活性成分木香烃内酯、去氢木香内酯、檀香醇、麝香酮、大黄素、大黄酚、大黄素甲醚、巴豆苷、厚朴酚及和厚朴酚也对ACh诱导的回肠平滑肌收缩有明显的抑制作用。结论WCA、EE、WE及其活性成分可能通过阻断回肠平滑肌细胞膜上的M3受体与ACh的结合,发挥促进肠平滑肌松弛的作用。     

Differential activities of decapeptide agonists of human C5a: the conformational effects of backbone N-methylation

Analogues of the potent, conformationally biased, decapeptide agonist of human C5a anaphylatoxin, C5a_65–74Y65,F67,P69,P71, -Ala73 (YSFKPMPLaR, peptide 54), were synthesized with methyl groups occupying specific amide nitrogen atoms along the peptide backbone. This N-methylation induced crucial extended backbone conformations in a manner similar to the two Pro residues, but without eliminating the contributions made by the side-chain of the residue for which Pro was substituted. The presence of backbone N-methyl groups on peptide 54 analogues had pronounced detrimental effects on the ability to bind and activate C5aRs expressed on human PMNs, but not on the ability to contract smooth muscle of human umbilical artery. Several N-methylated analogues of peptide 54 (peptides 56, 67, 124, 125, and 137) were significantly more selective for smooth muscle contraction, which is mediated by tissue resident macrophages, than for enzyme release from PMNs. Indeed, peptide 67, YSFKDMP(MeL)aR was almost 3000-fold more selective for smooth muscle contraction than for PMN enzyme release. Consistent with these differential activities was the observation that peptide 67 expressed a significantly greater binding affinity to C5aRs expressed on rat macrophages than on rat PMNs. This differential activity was also observed in vivo in the rat where peptide 67 induced a hypotensive response similar to peptide 54 and rhuC5a, but without accompanying neutropenia.     

罂粟科植物罂粟、延胡索和岩黄连镇痛作用的研究进展

疼痛是人类的第五大生命体征,既是机体的一种自我保护,同时也是机体对伤害性刺激的预警。尽管阿片类药物具有显著的不良反应及成瘾性,但目前该类药物仍是治疗严重急慢性疼痛的主要治疗药物。本文整理了具有镇痛功效的罂粟科植物罂粟、延胡索和岩黄连,从古籍记载、主要活性成分、药理作用和临床研究几个方面对其进行综述,以期更科学地发掘具有镇痛强,成瘾性低,毒副作用小的药物。     

Relaxant effect of Curcuma longa on rat tracheal smooth muscle and its possible mechanisms

Context: Turmeric is a spice obtained from the root of Curcuma longa L. (Zingiberaceae) with anti-aging, anticancer, anti-Alzheimer’s disease, antioxidant and other medicinal properties.

Objective: The relaxant effect of C. longa on rat tracheal smooth muscle and its possible mechanisms were investigated in this study.

Materials and methods: The relaxant effects of four cumulative concentrations of hydro-ethanol extract of C. longa (6.25, 12.5, 25, 50?mg/mL) were studied on tracheal smooth muscle precontracted by methacholine or KCl in non-incubated or incubated with different substances including propranolol, diltiazem, L-NAME, glibenclamide, atropine, chlorpheniramine, indomethacin and papaverine. The duration of the study was 84?days.

Results: In non-incubated tracheal smooth muscle, the extract of C. longa showed significant concentration-dependent relaxant effects (p?C. longa and theophylline in both methacholine and KCl-induced contraction conditions. In tissues incubated with propranolol, diltiazem, L-NAME and glibenclamide on methacholine-induced contraction and in tissues incubated with atropine, chlorpheniramine, indomethacin and papaverine on KCl-induced contraction, the extract also showed significant concentration-dependent relaxant effects (p?50 values of C. longa between non-incubated (16.22?±?0.62) and incubated tissues (atropine: 13.03?±?0.55, chlorpheniramine: 12.94?±?0.68, indomethacin: 14.80?±?0.57 and papaverine: 16.16?±?1.42) were not significantly different.

Conclusions: Tracheal smooth muscle relaxant effects of C. longa, were comparable to those of theophylline, which could be due to the presence of methylxanthines or its possible interaction with non-adrenergic non-cholinergic nervous system.