Carbachol阻断亚硒酸钠对离体皮质神经元的致凋亡作用(英文)

在早期工作发现小剂量亚硒酸钠 (Sodiumselenite)对离体皮质神经元的致凋亡作用的基础上 ,观察了在亚硒酸钠致凋亡模型中加入M型胆碱能受体激动剂Carbachol(Carb)能否阻止凋亡过程和相伴随的有关基因表达的改变。结果显示 :①用不同剂量 (0 .0 0 4 ,0 .0 2 ,0 .1,0 .5,2 .5和 12 .5mmol/L)的Carb和 0 .5μmol/L亚硒酸钠共同处理培养的新生小鼠皮质神经元时 ,用琼脂糖凝胶电泳DNA梯形检测和流式细胞仪亚二倍体峰检测 ,都证明Carb表现出对亚硒酸钠致凋亡作用的剂量依赖性保护效应 ;②用RT PCR技术证明 ,在与Carb共同孵育的实验中 ,不再出现或减弱了亚硒酸钠单独处理时出现的bcl 2基因表达的下调和bax ,p53,c fos以及AChE基因表达的上调。上述结果表明 ,亚硒酸钠对皮质神经元的致凋亡作用和与之相伴随的基因表达的改变 ,可被一定浓度的Carb所阻断 ,提示亚硒酸钠致凋亡作用可能同本室发现的 β 淀粉样蛋白的C末端 5肽片段的致凋亡作用具有类似的途径 ,以类似的基因表达改变为基础 ,并对Carb的抗凋亡机制进行了讨论。

TSH和Carbachol对甲状腺细胞内游离钙的动员作用

研究促甲状腺激素(TSH)和 Carbachol(Cch)对猪甲状腺细胞 Ca^(2+)的动员作用的结果表明,0.01～10mU/ml TSH 或10^(-5)～10^(-4)mol/L Cch 可引起甲状腺细胞[Ca^(2+)]急性升高.甲状腺细胞对 TSH 或 Cch 反应的敏感性在贴壁的单层细胞高于细胞悬液,在近汇合单层细胞高于汇合单层细胞。TSH 和 Cch 均能在无钙/EGTA 缓冲介质中刺激猪甲状腺细胞[Ca^(2+)]升高,提示此升高的[Ca^(2+)]源自细胞内储藏 Ca^(2+)的动员。

拟胆碱物质Carbachol对兔缺血心肌的兴奋性、不应期、传导性和自律性的影响

植物性神经对缺血心脏心律紊乱的发生起重要作用。近来有报导刺激迷走神经能提高心脏颤动阈和延缓缺血心脏心律紊乱的发生。也有报导拟副交感药物胆碱酯类有抗心律失常作用,其中尤以卡巴可(carbachol)的抗心律紊乱作用较强。本实验观察卡巴可对缺血心脏电生理特性的影响,分析副交感神经在心脏缺血时所能起的作用。动物心脏缺血模型有多种,最常用的是冠脉前降支闭塞法。应用此法测定心肌电生理特性的缺点是被测心脏及被测部位心肌缺血程度参差不一。

Carbachol promotes gastrointestinal function during oral resuscitation of burn shock

AIM: To investigate the effect of carbachol on gastrointestinal function in a dog model of oral resuscitation for burn shock. METHODS: Twenty Beagle dogs with intubation of the carotid artery, jugular vein and jejunum for 24 h were subjected to 35% total body surface area fullthickness burns, and were divided into three groups: no fluid resuscitation (NR, n = 10), in which animals did not receive fluid by any means in the first 24 h postburn; oral fluid resuscitation (OR, n = 8), in which dogs were gavaged with glucose-electrolyte solution (GES) with volume and rate consistent with the Parkland formula; and oral fluid with carbachol group (OR/CAR, n = 8), in which dogs were gavaged with GES containing carbachol (20 μg/kg), with the same volume and rate as the OR group. Twenty-four hours after burns, all animals were given intravenous fluid replacement, and 72 h after injury, they received nutritional support. Hemodynamicand gastrointestinal parameters were measured serially with animals in conscious and cooperative state. RESULTS: The mean arterial pressure, cardiac output and plasma volume dropped markedly, and gastrointestinal tissue perfusion was reduced obviously after the burn injury in all the three groups. Hemodynamic parameters and gastrointestinal tissue perfusion in the OR and OR/CAR groups were promoted to pre-injury level at 48 and 72 h, respectively, while hemodynamic parameters in the NR group did not return to pre-injury level till 72 h, and gastrointestinal tissue perfusion remained lower than pre-injury level until 120 h post-burn. CO 2 of the gastric mucosa and intestinal mucosa blood flow of OR/CAR groups were 56.4 ± 4.7 mmHg and 157.7 ± 17.7 blood perfusion units (BPU) at 24 h postburn, respectively, which were significantly superior to those in the OR group (65.8 ± 5.8 mmHg and 127.7 ± 11.9 BPU, respectively, all P < 0.05). Gastric emptying and intestinal absorption rates of GES were significantly reduced to the lowest level (52.8% and 23.7% of pre-injury levels) in the OR group at about 2 and 4 h post-burn, and did not return to 80% of pre-injury level until 24 h. In the first 24 h postburn, the rate of gastric emptying and intestinal water absorption were elevated by a mean 15.7% and 11.5%, respectively, in the OR/CAR group compared with the OR group. At 5 days, the mortality in the NR group was 30% (3/10), 12.5% in the OR group (1/8), and none in the OR/CAR group. CONCLUSION: Carbachol had a beneficial effect on oral resuscitation of burn shock by promoting gastric emptying and intestinal absorption in our canine model.

内源性阿片肽及K_(ATP)通道介导Carbachol引起的脊髓水平抗痛作用

采用记录大鼠伤害性屈肌反射积分肌电图的方法，观察了鞘内注入Ｃａｒｂａｃｈｏｌ（Ｃａｒ，胆硷能Ｍ受体激动剂）及吗啡引起的抗痛作用，并分析了纳洛酮（μ受体阻断剂）、优降糖（ＫＡＴＰ通道阻断剂）及阿托品对上述药物抗痛作用的影响，结果显示：①鞘内注入Ｃａｒ引起剂量依赖性的抗痛作用；②Ｃａｒ的抗痛作用可被鞘内予先注入纳洛酮或优降糖阻断；③鞘内注入吗啡引起的抗痛作用可被优降糖阻断，但不能被阿托品所阻断。这些结果提示：内源性阿片肽和ＫＡＴＰ通道介导了Ｃａｒ或乙酰胆硷引起的脊髓抗痛作用，在此过程Ｍ受体的激活引起内源性阿片肽的释放，后者通过打开ＫＡｒｐ通道实现镇痛。

Pharmacological effects of aqueous-ethanolic extract of Hibiscus rosasinensis on volume and acidity of stimulated gastric secretion

Objective:To explore the effects of extract of Hibiscus rosasinensis(H.rosasinensis) on the volume,free and total acidity of gastric secretion induced by carbachol.Methods:Animals were kept on fasting for 48 h.then the pylorus of each animal was ligated.They were randomly divided into 5 groups and treated by carbachol at 600μg/kg.Then animals in groupⅡ-Ⅴwere treated by H.rosasinensis extract at 250 and 500 mg/kg body weight,cimetidine at 2.5 mg/ kg and verapamil at 10 mg/kg body weight intraperitoneally,respectively.The volume,free and total acidity of gastric secretion were observed and compared.Results:It was found that the extract significantly reduced the volume,free and total acidity of gastric secretion(P【0.01). These reductions were comparable to cimetidine and verapamil.And the reduction in the volume and free acidity were more significant in cimetidine and verapamil treated group indicating that cimetidine and verapamil were more effective.Conclusions:The extract of H.rosasinensis can reduced the volume,free and total acidity of gastric secretion,and can be used effectively in the treatment of peptic ulcer.

Relationship between Carbachol Hyperstimulation-Induced Pancreatic Acinar Cellular Injury and Trypsinogen or NF-κB Activation in Rats in vitro

The relationship between M3 cholinergic receptor agonist （carbachol） hyperstimulationinduced pancreatic acinar cellular injury and trypsinogen activation or NF-κB activation in rats was studied in vitro. Rat pancreatic acinar ceils were isolated, cultured and treated with carbachol, the active protease inhibitor （pefabloc）, and NF-κB inhibitor （PDTC） in vitro. Intracellular trypsin activity was measured by using a fluorogenic substrate. The cellular injury was evaluated by measuring the leakage of LDH from pancreatic acinar ceils. The results showed that as compared with control group, 10-3 mol/L carbachol induced a significant increase of the intracellular trypsin activity and the leakage of LDH from pancreatic acinar cells. Pretreatment with 2 mmol/L pefabloc could significantly decrease the activity of trypsin and the leakage of LDH from pancreatic acinar cells （P〈0. 01） following the treatment with a high concentration of carbachol （10^-3 mol/L） in vitro. The addition of 10^-2mol/L PDTC didn＇t result in a significant decrease in the activity of trypsin and the leakage of LDH from pancreatic acinar cells treated with a high concentration of carbachol （10^-3 mol/L） in vitro （P〉0. 05）. It was concluded that intracellular trypsinogen activation is likely involved in pancreatic acinar cellular injury induced by carbachol hyperstimulation in vitro. NF-κB activation may not be involved in pancreatic acinar cellular injury induced by carbachol hyperstimulation in vitro.

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastrointestinal

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

We acknowledge our sincere thanks to our reviewers. Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of our World Series Journals. Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers for reviewing the articles(either published or rejected) over the past period of time.

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics. The editors

Acknowledgments to reviewers of World Journal of Gastrointestinal Pharmacology and Therapeutics

Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Gastrointestinal Pharmacology and Therapeutics.The editors and authors of the articles submitted to the journal are grateful to the

卡巴胆碱对失血性休克大鼠肺微血管内皮细胞功能的影响

目的 观察大鼠失血性休克时卡巴胆碱对肺微血管内皮细胞的作用。方法 将30只健康雄性SD大鼠(SPF级)按每组10只随机分为假休克组(SS组)、失血性休克组(HS组)、失血性休克+卡巴胆碱组(CBL组)。失血性休克动物模型按照Wiggers改良法制作,各组模型制备完毕后6 h,经右侧股动脉采血,检测肿瘤坏死因子-α(TNF-α)水平,取右肺下叶肺组织检测Src抑制的蛋白激酶C的底物(SSeCKS)、E-选择素蛋白质水平,取右肺下叶行透射电镜检查肺微血管内皮细胞超微结构。结果 SS组表达少量的TNF-α、SSeCKS、E-选择素,HS组和CBL组表达升高(P<0.05),与HS组相比,CBL组表达降低(P<0.05)。SS组肺微血管内皮细胞细胞膜表面光滑,细胞膜、细胞质、细胞核形态结构正常;HS组肺微血管内皮细胞出现细胞水肿、坏死和凋亡表现(细胞膜表面皱折、细胞膜表面凹凸不平、细胞器水肿、异染色质染色加深边集等);CBL组较SS组,细胞有所损伤,但好于HS组。结论 大鼠失血性休克时卡巴胆碱对肺微血管内皮细胞具有保护作用,也可通过抑制炎症细胞合成和释放炎症介质减轻对血管内皮细胞的损伤。

痰热清注射液治疗慢性阻塞性肺病急性加重期作用机制探讨

目的:研究痰热清注射液治疗慢性阻塞性肺病急性加重期作用机制。方法:在线查询TCMSP数据库、既往文献获取黄芩、熊胆粉、山羊角、金银花、连翘等中药的主要活性成分,利用swisstargetprediction数据库获取其活性成分对应靶点;利用GeneCards、OMMI、Drug Bank等数据库获取慢性阻塞性肺病急性加重期靶点。利用Venny平台在线获取药物与疾病靶点交集,通过DAVID数据库对相交靶点进行基因本体分析和通路富集分析,使用STRING数据库构建蛋白相互作用网络,借助Cytoscapr软件行可视化处理并筛选主要活性成分、关键靶点。最后通过AutoDock vina软件将核心靶点与核心成分进行分子对接验证,并利用pymol可视化处理。结果:痰热清注射液中含主要活性成分90个,对应靶点557个;连翘、黄芩、金银花为痰热清注射液的关键作用药物;baicalein、Norwogonin、5,7,4’-Trihydroxy-8-methoxyflavone、5,2’,6’-Trihydroxy-7,8-dimethoxyflavone、(2R)-7-hydroxy-5-methoxy-2-phenylchroman-4-one、Panicolin、Skullcapflavone II、Moslosooflavone、5,7,2,5-tetrahydroxy-8,6-dimethoxyflavone、quercetin等为核心活性成分;STAT3、HSP90AA1、ESR1、SRC、EP300、AKT1、JUN、PIK3R1、RELA等靶点为蛋白互作网络中的核心靶点。结论:痰热清注射液治疗主要通过黄酮类物质调节细胞炎症反应、细胞增殖、凋亡等对慢性阻塞性肺病急性加重期发挥潜在作用。

基于网络药理学及分子对接探讨二至丸治疗早发性卵巢功能不全的作用机制

目的基于网络药理学方法探讨二至丸治疗早发性卵巢功能不全(POI)的可能分子作用机制。方法使用网络药理学平台(TCMSP)采集二至丸的有效成分和相关的基因;通过基因组注释数据平台(GeneCards)、人类孟德尔遗传数据库(OMIM)数据库获取POI疾病靶点;用蛋白互作网络数据库(STRING)构建蛋白质相互作用网络(PPI),通过CytoHubba筛选核心靶点。使用生物学信息注释数据库(DAVID)平台进行富集分析,采用Cytoscape 3.10.0软件进行拓扑学分析,利用AutoDockTools进行分子对接。结果二至丸内最主要的有效成分为槲皮素、木犀草素、山柰酚、刺槐素等,其中的AKT1、TP53等是关键靶点,包含的通路主要为PI3K-Akt信号通路、流体剪切应力和动脉粥样硬化信号通路等。分子对接验证大部分靶点与成分能进行有效结合。结论揭示二至丸能够经多种成分、靶点及多条信号通路对POI发挥协同治疗作用。

槲皮素与芦丁对离体大鼠主动脉环的舒张作用及机制

目的:比较研究槲皮素与芦丁对离体大鼠胸主动脉环的作用及其可能的途径。方法:采用累积加药法,检测槲皮素和芦丁对去氧肾上腺素(pheny lephrine,PE)预收缩的胸主动脉环张力的影响。结果:槲皮素对离体大鼠内皮完整和去内皮的胸主动脉环均有浓度依赖性的舒张作用,而芦丁对PE预收缩血管的舒张作用是内皮依赖性的。槲皮素和芦丁对内皮完整的胸主动脉环的最大舒张反应分别为(77.20±6.11)%和(44.28±7.48)%,但两者对内皮完整的胸主动脉环最大舒张的半数有效浓度无明显差异。用一氧化氮合酶抑制剂L-NAM E(0.1 mm o l/L)预处理后,可阻断芦丁诱导的舒张血管作用,但不能阻断槲皮素引起的舒张血管作用;用鸟苷酸环化酶抑制剂亚甲蓝(10μm o l/L)预处理后,两者的血管舒张作用均被阻断。用环氧合酶抑制剂吲哚美辛(10μm o l/L)预处理后可减弱槲皮素诱导的舒张血管作用,但不能阻断芦丁引起的舒张血管作用。结论:槲皮素的舒血管作用强于芦丁,槲皮素可能是通过鸟苷酸环化酶和环氧合酶途径产生非内皮依赖性的血管舒张作用,而芦丁可能是通过NO-鸟苷酸环化酶途径产生内皮依赖性的血管舒张作用。

慢性癫痫对大鼠空间记忆再生能力的影响

目的 :探讨慢性癫痫对大鼠空间记忆再生能力的影响 ,检测组胺前体物质组氨酸和胆碱酯酶抑制剂TAK- 14 7对癫痫诱发记忆障碍的作用。方法 :大鼠在放射状八臂 (四臂放食物 )迷宫训练成功后 ,隔日腹腔注射亚惊厥剂量 ( 35 mg/ kg)的戊四唑 ,直至完全点燃。完全点燃后在同一迷宫中测记忆的再现过程。结果 :完全点燃后第1d至第 18d,大鼠在放射状迷宫中的错误次数较对照组明显上升 ,且维持在一相对平衡的状态 ,31d后与对照组一致。TAK- 14 7剂量依赖性地改善了癫痫诱发的空间记忆再现障碍 ,包括参考记忆和工作记忆。组氨酸剂量依赖性地改善参考记忆 ,不影响工作记忆。结论 :戊四唑点燃癫痫可导致大鼠空间记忆再生能力下降 。

卡巴胆碱对脂多糖刺激巨噬细胞释放炎症细胞因子的影响及其受体研究

目的在体外脂多糖(lipopolysaccharide,LPS)刺激大鼠腹腔巨噬细胞炎症模型中观察拟胆碱药卡巴胆碱对炎症细胞因子释放的影响,并研究其受体途径。方法采集大鼠腹腔巨噬细胞,先给予M样胆碱能受体拮抗剂阿托品或N样胆碱能受体α7亚基特异性拮抗剂α-银环蛇毒素,15min后给予卡巴胆碱或N样胆碱能激动剂烟碱,15min后再给予LPS刺激,4～6h后取细胞培养上清液,ELISA法检测促炎细胞因子TNF-α、IL-6水平和抗炎细胞因子IL-10水平。大鼠腹腔巨噬细胞制作细胞爬片,用高浓度烟碱和卡巴胆碱处理15min后加入异硫氰酸荧光素标记的α-银环蛇毒素(FITC-α-Bgt),在激光扫描共聚焦显微镜下观察结果并摄片。结果卡巴胆碱与烟碱均能抑制LPS刺激后TNF-α、IL-6的释放,对IL-10的释放无影响。阿托品预处理后,卡巴胆碱与烟碱对TNF-α、IL-6释放的抑制作用无明显变化(P>0.05);α-银环蛇毒素预处理后,卡巴胆碱与烟碱对两种促炎细胞因子释放的抑制作用明显减弱(P<0.01)。激光共聚焦显微镜结果显示烟碱和卡巴胆碱处理后,FITC-α-Bgt与细胞的结合被减弱。结论卡巴胆碱在LPS刺激大鼠腹腔巨噬细胞模型中具有抗炎作用,此作用不能被阿托品阻断,可以被α-银环蛇毒素拮抗。表明卡巴胆碱的抗炎作用与烟碱相似,都是通过N样胆碱能受体α7亚基实现的。

黄芪舒张血管平滑肌的作用及机制

目的 :探讨黄芪对血管平滑肌的舒张作用及其机制。方法 :采用大鼠离体胸主动脉环灌流模型。在去除血管环内皮后 ,观察累积浓度黄芪对基础状态 (基础组 )、苯肾上腺素 (PE)预收缩 (苯肾上腺素组 )、氯化钾预收缩(氯化钾组 )的血管环的作用和黄芪对经无钙液 (无钙液组 )、无钙液加肝素 (肝素组 )、普萘洛尔 (普萘洛尔组 )预处理后的血管环的作用。结果 :在血管内皮被去除后 ,黄芪对基础状态或氯化钾预收缩的血管环无影响 ;当黄芪浓度累积达 (10 -1、3× 10 -1、10 0 、3× 10 0 ) g/L时 ,对 PE(3× 10 -7mol/L)预收缩的血管环产生剂量依赖性舒张作用 (P<0 .0 5 )。经无钙液预处理后 ,黄芪 (3× 10 0 g/L )对血管环的舒张作用未被阻断 ;但经无钙液加肝素预处理后 ,该作用被显著抑制 (P<0 .0 1) ;而普萘洛尔预处理不影响黄芪对 PE预收缩血管环的舒张作用。结论 :黄芪对去除内皮的血管具有舒张作用。其机制可能与阻断血管平滑肌细胞内质网上的三磷酸肌醇敏感的钙离子通道 ,抑制内钙的释放有关。