胆碱能拮抗剂

摘要： [目的]探讨长托宁联合连续性肾脏替代治疗(CRRT)对急性重度有机磷农药中毒患者的治疗效果.[方法]就诊于本院的急性重度有机磷农药中毒的患者60例随机分为观察组与对照组,每组各30例.对照组患者应用长托宁治疗,观察组在此基础上联合CRRT治疗,比较两组患者的临床疗效及血清炎症指标变化.[结果]观察组患者的存活率(93.33％)高于对照组(80％)(P>0.05);观察组存活患者的苏醒时间、全血胆碱酯酶活力恢复时间较对照组明显缩短(P<0.05);治疗后两组患者的C反应蛋白(CRP)、肿瘤坏死因子-ɑ(TNF-ɑ)水平均较入院时明显降低(P<0.05),且治疗后观察组的CRP、TNF-ɑ水平明显低于对照组(P<0.05).[结论]长托宁联合CRRT治疗有机磷农药中毒患者具有较好的疗效,能有效清除患者的炎症因子,缩短患者的苏醒时间、全血胆碱酯酶活力恢复时间,提高治疗效果.

摘要： Objective To evaluate the effects of penehyclidine hydrochloride on the nuclear factor erythroid 2-related factor 2/antioxidant responsive element (Nrf2/ARE) signaling pathway during endotoxin-induced acute lung injury(ALI) in neonate rats.Methods Forty 7-day-old Wistar rats weighing 12-18 g were randomly divided into 4 groups (n=10) using a random number table:normal saline group(NS group),acute lung injury(ALI group),penehyclidine hydroehloride group(PHC group) and penehyclidine hydrochloride + Nrf2 siRNA plasmid group(PNS group).The ALI model was induced with intraperitoneal endotoxin (5.0 mg/kg) in groups ALI,PHC and PNS.In groups PHC and PNS,penehyclidine hydrochloride (2.0 mg/kg) was injected intraperitoneally at 1 h before ALI respectively,while the equal volume of normal saline was administered in groups NS and ALI.The animal of PNS group were inhaled adenovirus packaging of Nrf2-siRNA three times (one time a day) before modeling.At 4 h after endotoxin injection,the rats were sacrificed.The lungs were collected to determine the wet/dry(W/D) lung weight ratio.The expression of Nrf2 and heme oxygen and enzyme 1(HO-1) were determined by Western blotting,contents of tumor necrosis factor-alpha(TNF-α),interleukinl0 (IL-10)were determined by enzyme-linked immunosorbent assay(ELISA).The cell apoptosis were determined by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling(TUNEL),and the apoptotic index was calculated.Results The W/D ratio in NS,ALI,PHC and PNS groups were(4.2±0.1),(9.6±0.7),(6.5±0.6),(8.3± 1.3)respectively.The apoptotic index were(3.7±0.5)％,(31.5±3.2)％,(17.6±4.2)％,(28.1 ±3.5)％respectively.The contents of TNF-c were(10.3± 1.6),(98.5±8.5),(68.5 ±6.7),(89.9±8.5)pg/ml respectively.The contents of IL-10 were (7.9±0.6),(102.8±9.3),(72.5±5.8),(97.7±9.1)pg/ml respectively.The expression of Nrf2 were (23.2±7.6),(79.8± 13.0),(155.5± 16.7),(12.0±3.3)respectively.The expression of HO-1 were(31.7 ± 8.6),(90.8 ± 10.3),(147.6 ± 22.5),(61.4 ± 9.7) respectively.There were statistically significant differences among different groups(F=86.013,154.897,328.810,374.198,333.965,125.274,all P＜0.05).Compared with group NS,the W/D ratio,apoptotic index and the contents of TNF-α,IL-10 increased,the expression of Nrf2 and HO-1 up-regulated in group ALI and group PHC(all P＜0.05).Compared with group ALI,the W/D ratio,apoptotic index and the contents of TNF-α,IL-10 decreased,the expression of Nrf2 and HO-1 up-regulated in group PHC (all P＜0.05).Compared with group ALI,no significant differences were found in the W/ D ratio,apoptotic index and the contents of TNF-α,IL-10 in group PNS(all P＞0.05),while the expression of Nrf2 and HO-1 down-regulated in group PNS(all P＜0.05).Compared with group PHC,the W/D ratio,apoptotic index and the contents of TNF-α,IL-10 increased,the expression of Nrf2 and HO-1 down-regulated in group PNS(all P＜0.05).Conclusion Nrf2/ARE signaling pathway is involved in the reduction of ALI by penehyclidine hydrochloride in neonate rats.%目的 评价盐酸戊乙奎醚对新生大鼠内毒素急性肺损伤(ALI)时肺组织核因子E2相关因子-2 (Nrf2)/抗氧化反应元件(ARE)信号通路的影响.方法 清洁级健康雄性Wistar大鼠40只、体质量12～ 18 g,7日龄.采用随机数字表法分为4组(n=10):对照组(NS组)、急性肺损伤组(ALI组)、盐酸戊乙奎醚组(PHC组)和盐酸戊乙奎醚+Nrf2-siRNA质粒组(PNS组).腹腔注射内毒素5.0 mg/kg制备ALI模型.PHC组和PNS组于内毒素注射前1h腹腔注射盐酸戊乙奎醚2.0 mg/kg,NS组和ALI组给予等容量生理盐水.PNS组新生大鼠进行模型制备前3d,吸入采用腺病毒包装的Nrf2-siRNA液3次(1次/d).于注射内毒素4h时处死大鼠取肺组织标本,计算肺组织湿/干重比(W/D),采用免疫印迹法(Western blotting)测定Nrf2和血红素氧合酶-1(HO-1)的表达,采用酶联免疫吸附测定法(ELISA)测定肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)的含量;脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)计数凋亡细胞,计算细胞凋亡指数(AI).结果 NS组、ALI组、PHC组、PNS组W/D分别为(4.2±0.1)、(9.6±0.7)、(6.5±0.6)、(8.3±1.3),AI分别为(3.7±0.5)％、(31.5±3.2)％、(17.6±4.2)％、(28.1±3.5)％,TNF-α分别为(10.3±1.6)、(98.5±8.5)、(68.5±6.7)、(89.9±8.5)pg/ml,IL-10分别为(7.9±0.6)、(102.8±9.3)、(72.5±5.8)、(97.7±9.1) pg/ml,Nrf2分别为(23.2±7.6)、(79.8±13.0)、(155.5±16.7)、(12.0±3.3),HO-1分别为(31.7±8.6)、(90.8±10.3)、(147.6±22.5)、(61.4±9.7),差异均有统计学意义(F=86.013、154.897、328.810、374.198、333.965、125.274,均P＜0.05);与NS组相比较,ALI组和PHC组肺组织W/D、AI和TNF-α、IL-10含量升高,Nrf2和HO-1的表达上调(均P＜0.05);与ALI组相比较,PHC组肺组织W/D、AI和TNF-α、IL-10含量下降,Nrf2和HO-1的表达上调(均P＜0.05);与ALI组相比较,PNS组肺组织W/D、AI和TNF-α、IL-10含量差异均无统计学意义(均P＞0.05),Nrf2和HO-1的表达下调(均P＜0.05);与PHC组相比较,PNS组肺W/D、AI和TNF-α、IL-10含量升高,Nrf2和HO-1表达下调(均P＜0.05).结论 Nff2/ARE信号通路参与了盐酸戊乙奎醚减轻新生大鼠内毒素性ALI.

摘要： 目的 评价盐酸戊乙奎醚对大鼠内毒素性肺损伤时小窝蛋白-1(Cav-1)表达的影响.方法 SPF级健康雄性SD大鼠30只,体重170～ 190 g,采用随机数字表法分为3组(n=10):对照组(C组)、内毒素性肺损伤组(LI组)和盐酸戊乙奎醚组(PHCD组).采用气管内注射LPS 0.2 ml(5mg/kg)的方法制备内毒素性肺损伤模型.PHCD组于模型制备前1h腹腔注射盐酸戊乙奎醚2mg/kg(0.5 ml).于模型制备后24 h时,取动脉血样,进行血气分析,采用ELISA法检测血清TNF-α和IL-1β浓度.随后处死大鼠,进行支气管肺泡灌洗,收集支气管肺泡灌洗液(BALF),计算PMNs百分比;取肺组织,观察病理学结果,采用比色法测定髓过氧化物酶(MPO)活性,计算湿重/干重比值(W/D比值);采用Western blot法测定Cav-1和核蛋白NF-κB的表达水平.结果 与C组比较,LI组pH值和PaO2降低,PaCO2、BALF PMNs百分比、W/D比值和MPO活性升高,Cav-1表达下调,核蛋白NF-κB表达上调,血清TNF-α和IL-1β浓度升高(P＜0.05).与LI组比较,PHCD组pH值和PaO2升高,PaCO2、BALF PMNs百分比、肺组织W/D比值和MPO活性降低,Cav-1表达上调,核蛋白NF-κB表达下调,血清TNF-α和IL-1β浓度降低(P＜0.05),肺组织病理学损伤减轻.结论 盐酸戊乙奎醚减轻大鼠内毒素性肺损伤的机制可能与上调肺组织Cav-1表达,减轻炎症反应有关.%Objective To evaluate the effect of penehyclidine hydrochloride (PHC) on the expression of caveolin-1 (Cav-1) with lipopolysaccharide (LPS)-induced lung injury (LI) in rats.Methods Thirty SPF healthy male Sprague-Dawley rats,weighing 170-190 g,were divided into 3 groups (n =10each) using a random number table method:control group (group C),LPS-induced LI group (group LI)and PHCD group.LI was produced by injecting LPS 0.2 ml (5 mg/kg) via the trachea in anesthetized rats.PHCD 0.5 ml (2 mg/kg) was intraperitoneally injected at 1 h before establishing the model in group PHCD.Arterial blood samples were collected at 24 h after establishing the model for blood gas analysis and for determination of serum tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) concentrations by enzyme-linked immunosorbent assay.Rats were then sacrificed,and the lungs were removed.The main bronchus was lavaged,and the broncho-alveolar lavage fluid (BALF) was collected for calculation of the percentage of polymorphonuclear neutrophils (PMNs).Lung tissues were obtained for examination of pathological changes and for determination of myeloperoxidase (MPO) activity (by colorimetric assay),wet/dry weight ratio (W/D ratio),and expression of Cav-1 and nuclear factor kappa B (NF-sB) in nucleoprotein (by Western blot).Results Compared with group C,pH value and PaO2 were significantly decreased,the PaCO2,percentage of PMNs in BALF,W/D ratio and MPO activity were increased,the Car-1 expression was down-regulated,the expression of NF-κB in nucleoprotein was up-regulated,and the serum TNF-α and IL-1β concentrations were increased in group LI (P＜0.05).Compared with group LI,pH value and PaO2 were significantly increased,the PaCO2,percentage of PMNs in BALF,W/D ratio and MPO activity were decreased,the Cav-1 expression was up-regulated,the expression of NF-κB in nucleoprotein was down-regulated,and the serum TNF-α and IL-1β concentrations were decreased (P＜0.05),and the path ological changes of lung tissues were significantly attenuated in group PHCD (P＞0.05).Conclusion The mechanism by which PHC reduces LPS-induced LI may be related to up-regulating the expression of Cav-1 and mitigating inflammatory responses in lung tissues of rats.

摘要： Objective To observe the efficacy and feasibility of a new therapy using a combination of different anticholinergic eyedrops in controlling myopia progression and axial prolongation in adolescents.Methods Between July 2013 and June 2014,a total of 150 myopia adolescents aged 6-12 years were recruited at the clinic of Tongji Hospital in Shanghai.Participants were assigned in a 1∶ 2∶2 ratio to placebo group (no medication),combined treatment group (0.5％ racanisodamine eyedrops were used twice a day during semesters,1％ atropine eyedrops were used before sleep during vacation) and atropine group (1％ atropine eyedrops were used before sleep everyday).All subjects wore glasses.Visual acuity,best corrected visual acuity,cycloplegic refraction,corneal curvature,axial length,intraocular pressure,fundus and adverse events were recorded every 6 months during follow-up for 24 months.Results At baseline,there was no significant difference in age,equivalent spherical mirror number and axial length among the three groups (all P＞0.05).At the end of the second year,the mean myopia progression (changes of spherical equivalent) was-2.34 (-2.93,-1.75) D,-0.63 (-1.00,-0.50) D and-0.25 (-0.50,-0.06) D in placebo group,combined treatment group and atropine group,respectively (P＜0.001),and there was statistically significant difference between each two groups (all P＜0.001).The axial length change of each group were (1.51±0.23) mm,(0.69±0.30) mm and (0.31±0.30) mm,respectively (P＜0.001),and there was statistically significant difference between each two groups (all P＜0.001).Conclusion Therapy using a combination of different anticholinergic eyedrops can effectively control the progression of myopia and axial prolongation in adolescents,and increase the compliance of children and the safety of drug use.%目的 观察消旋山莨菪碱联合阿托品滴眼液对控制青少年近视进展和眼轴延长的有效性和可行性.方法 随机对照临床试验.2013年7月至2014年6月招募150名6～12岁在上海市同济医院眼科门诊就诊的近视青少年.“信封法”顺序编码对应计算机随机方案,按1∶2∶2分为对照组(不使用药物)、联合组(0.5％消旋山莨菪碱滴眼液早晚学期内使用,联合1％阿托品眼用凝胶假期每晚使用)和阿托品组(每晚使用1％阿托品眼用凝胶).所有研究对象均戴镜足矫.随访24个月,每6个月记录双眼裸眼视力、最佳矫正视力、等效球镜度数、角膜曲率、眼轴长度及不良事件.结果 三组入组时年龄、等效球镜度数、眼轴长度比较差异均无统计学意义(均P＞0.05).24个月时三组等效球镜度数变化量分别为:对照组-2.34(-2.93,-1.75)D、联合组-0.63(-1.00,-0.50)D、阿托品组-0.25(-0.50,-0.06)D(P＜0.001),两两比较差异均有统计学意义(均P＜0.001);眼轴变化量分别为:对照组(1.51±0.23)mm、联合组(0.69±0.30)mm、阿托品组(0.31±0.30) mm (P＜0.001),两两比较差异均有统计学意义(均P＜0.001).结论 消旋山莨菪碱联合阿托品滴眼液能有效控制青少年近视进展及眼轴增长,同时增加患儿的依从性和药物使用的安全性.

摘要： 目的 评价盐酸戊乙奎醚预先给药对大鼠心肌缺血再灌注时核因子E2相关因子2(Nrf2)/抗氧化反应序列原件(ARE)信号通路的影响.方法 清洁级健康雄性SD大鼠36只,体重220～240 g,2～3月龄,采用随机数字表法分为3组(n=12):假手术组(S组)、心肌缺血再灌注组(Ⅰ/R组)和盐酸戊乙奎醚预先给药组(PHC组).采用结扎左冠状动脉前降支30 min恢复灌注的方法制备大鼠心肌缺血再灌注损伤模型.于缺血前30 min时PHC组腹腔注射盐酸戊乙奎醚2 mg/kg,S组仅穿线,不结扎.于再灌注120 min时处死大鼠取心脏,采用TTC法确定心肌梗死体积,计算心肌梗死体积百分比,TUNEL法检测凋亡心肌细胞,计算细胞凋亡指数,Western blot法和实时荧光定量PCR法分别检测Nrf2、血红素氧合酶-1(HO-1)、醌氧化还原酶1(NQO1)、γ-谷氨酸半胱氨酸合成酶(γ-GCS)及其mRNA表达.结果 与S组比较,Ⅰ/R组和PHC组心肌梗死体积百分比和细胞凋亡指数增加,Nrf2、HO-1、NQO1、γ-GCS及其mRNA表达下调(P＜0.05);与Ⅰ/R组比较,PHC组心肌梗死体积百分比和细胞凋亡指数降低,Nrf2、HO-1、NQO1、γγ-GCS及其mRNA表达上调(P＜0.05).结论 盐酸戊乙奎醚预先给药通过激活Nrf2/ARE信号通路减轻大鼠心肌缺血再灌注损伤.%Objective To evaluate the effect of penehychdine hydrochloride pretreatment on nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway during myocardial ischemia-reperfusion (Ⅰ/R) in rats.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 2-3 months,weighing 220-240 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),myocardial Ⅰ/R group and penehyelidine hydrochloride pretreatment group (group PHC).Myocardial Ⅰ/R was induced by occlusion of the anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion.At 30 min before ischemia,penehyelidine hydrochloride 2 mg/kg was injected intraperitoneally in group PHC,and the anterior descending branch of left coronary artery was only exposed but not ligated in group S.Rats were sacrificed at the end of reperfusion,and hearts were removed for measurement of the myocardial infarct size (by 2,3,5-triphenyltetrazolium chloride staining),cell apoptosis (by TUNEL) and expression of Nrf2,heme oxygenase-1 (HO-1),NQO1 and γ-glutamylcysteine synthetase (γ-GCS) protein and mRNA (by using Western blot or real-time fluorescence quantitative polymerase chain reaction).The percentage of myocardial infarct size and apoptosis index were calculated.Results Compared with group S,the percentage of myocardial infarct size and apoptosis index were significantly increased,and the expression of Nrf2,HO-1,NQO1 and γ-GCS protein and mRNA was down-regulated in Ⅰ/R and PHC groups (P＜0.05).Compared with group l/R,the percentage of myocardial infarct size and apoptosis index were significantly decreased,and the expression of Nrf2,HO-1,NQO1 and γ-GCS protein and mRNA was up-regulated in group PHC (P＜0.05).Conclusion Penehyclidine hydrochloride pretreatment attenuates myocardial Ⅰ/R injury through activating Nrf2-ARE signaling pathway in rats.

摘要： 本发明涉及包含局部用(吸入)抗胆碱能药和吸入或口服白三烯(LT)受体拮抗剂(BLT-和CysLT-受体拮抗剂)的用于治疗呼吸系统疾病包括过敏性鼻炎、支气管哮喘和慢性阻塞性肺病(COPD)的组合。本发明进一步包含该组合以局部应用(吸入)制剂的呈现和在例如

摘要： 昆虫的烟碱能乙酰胆碱受体的兴奋剂或拮抗剂防治体内寄生虫的应用。

摘要： 本发明涉及组胺‑3受体反向激动剂、乙酰胆碱酯酶抑制剂和NMDA受体拮抗剂的组合。此外，本发明提供了与乙酰胆碱酯酶抑制剂和N‑甲基‑D‑天冬氨酸(NMDA)受体拮抗剂组合或作为其辅助的组胺‑3受体(H3R)反向激动剂或其可药用盐，及其在治疗认知障碍中的用途。本发明还提供了含有所述组合的药物组合物。

摘要： 阿吡巴替丁(Epibatidine)及其衍生物可用作胆碱能受体激动剂和拮抗剂。

摘要： 本发明涉及包含局部用(吸入)抗胆碱能药和吸入或口服白三烯(LT)受体拮抗剂(BLT－和CysLT－受体拮抗剂)的用于治疗呼吸系统疾病包括过敏性鼻炎、支气管哮喘和慢性阻塞性肺病(COPD)的组合。本发明进一步包含该组合以局部应用(吸入)制剂的呈现和在例如Novolizer

摘要： 本发明公开了调节哺乳动物胆碱能功能的药物组合物和方法，所述的药物组合物包括NRPA化合物或其药物上可接受的盐和止吐药/止恶心药或药物上可接受的盐以及药物上可接受的载体，所述的方法包括给药NRPA化合物或其药物上可接受的盐和止吐药/止恶心药或药物上可接受的盐以及药物上可接受的载体。所述的NRPA化合物和止吐药/止恶心药的含量使得该组合物可有效调节胆碱能功能或治疗疾病或疾患，所述的疾病或疾患选自肠炎病(包括、但不限于溃疡性结肠炎、坏疽性脓皮病和局限性回肠炎)、过敏性肠综合征、强直性张力障碍、慢性疼痛、急性疼痛、口炎性腹泻、囊炎、血管收缩、焦虑、惊恐性障碍、抑郁症、双相性精神障碍、孤独症、睡眠障碍、射精迟缓、肌萎缩性侧索硬化症(ALS)、认知功能障碍、高血压、食欲过盛、食欲缺乏、肥胖、心律失常、胃酸分泌过多、溃疡、嗜铬细胞瘤、进行性核上麻痹、化学品依赖和成瘾(例如烟碱(和/或烟草产品)、酒精、苯并二氮杂庚因、巴比妥酸盐、阿片类或可卡因依赖或成瘾)、头痛、偏头痛、中风、外伤性脑损伤(TBI)、强迫性神经失调(OCD)、精神病、亨廷顿舞蹈病、迟发性运动障碍、运动过度、朗读困难、精神分裂症、多发性脑梗塞死性痴呆、与年龄相关的认知能力下降、包括无癫痫小发作在内的癫痫、阿尔茨海默样老年性痴呆(AD)、帕金森病(PD)、注意力不集中的过度反应症(ADHD)和图雷特综合征。本发明还公开了这些组合物的使用方法。

摘要： 昆虫的烟碱能乙酰胆碱受体的兴奋剂或拮抗剂防治体内寄生虫的应用。

摘要： 本发明涉及组胺‑3受体反向激动剂、乙酰胆碱酯酶抑制剂和NMDA受体拮抗剂的组合。此外，本发明提供了与乙酰胆碱酯酶抑制剂和N‑甲基‑D‑天冬氨酸(NMDA)受体拮抗剂组合或作为其辅助的组胺‑3受体(H3R)反向激动剂或其可药用盐，及其在治疗认知障碍中的用途。本发明还提供了含有所述组合的药物组合物。

摘要： 本发明涉及适用于治疗与帕金森病中的多巴胺激动剂疗法相关的运动障碍的新组合产品、其制备以及其作为药物的用途和包含其的药物，所述组合产品包含作为活性成分的至少一种低分子量烟碱性乙酰胆碱受体α7活化剂和至少一种低分子量代谢型谷氨酸受体5拮抗剂。

摘要： 本文提供了治疗癌症(例如，NSCLC)的方法，其包括向有此需要的人患者施用：(a)PD‑1拮抗剂；(b)ILT4拮抗剂；和(c)一种或多种化学治疗剂。还提供了用于治疗癌症的含有此类药剂的药物组合物和试剂盒。