Apelin/APJ受体在脂肪乳剂解救布比卡因心脏毒性中的作用及机制研究
项目来源
国(略)科(略)((略)C(略)
项目主持人
徐(略)
项目受资助机构
温(略)大(略)
项目编号
8(略)0(略)
立项年度
2(略)
立项时间
未(略)
研究期限
未(略) (略)
项目级别
国(略)
受资助金额
7(略)0(略)
学科
医(略)-(略)统(略)损(略)复(略)和(略)
学科代码
H(略)2(略)2(略)
基金类别
面(略)
关键词
A(略);(略)卡(略) (略)l(略);(略)毒(略) (略)剂(略)A(略);(略)卡(略) (略)l(略);(略)毒(略) (略)剂
参与者
吴(略)学(略)权(略)赛(略)聪(略)娇(略)施(略)仙(略)
参与机构
美(略)俄(略)学
项目标书摘要:以布(略)类局麻药在麻醉领域(略)出,一旦入血量偏大(略)甚至心脏停搏,常规(略)期研究中发现,脂肪(略)救治与其脂质包裹((略)有关,但不能完全以(略)"解释。Apeli(略)剂均具有正性肌力作(略)释放和mPTP开放(略)lin/APJ受体(略)心脏毒性中的作用及(略)。本课题拟通过膜片(略)lot、RT-PC(略)究Apelin/A(略)中发挥作用的具体机(略)对脂肪乳剂救治效果(略)究,阐明Apeli(略)剂解救布比卡因心脏(略),为局麻药心脏毒性(略)思路。
Applicati(略): Long-ac(略) local an(略)articular(略)ine,are w(略)ed in ane(略) to their(略)t cardiac(略)ocal anes(略) lead to (略)ulatory c(略) cardiac (略)bsorbed i(略)ream in l(略)e.And sta(略)citation (略)rk effect(略)revious s(略)ed that l(略)itation o(略)sthetic-i(略)iac toxic(略)tially as(略)th"Lipid (略)ould not (略)plained b(略)k".Simila(略)emulsion,(略)receptor (略) inotropi(略) well as (略)protectio(略)nhibiting(略)g of mPTP(略)ng ROS.Ho(略)ole of Ap(略)ceptor on(略)scitation(略)aine-indu(略) toxicity(略)en studie(略)ed.This s(略)nvestigat(略)nism of A(略)eceptor o(略)uscitatio(略)ffects of(略)Apelin on(略)scitation(略)g patch c(略)que,Weste(略)lysis,RT-(略)ansfectio(略)oal of th(略) to illus(略)ffects an(略) of Apeli(略)tor on li(略)tation of(略)e-induced(略)xicity,an(略)xperiment(略)d new met(略)e treatme(略) anesthet(略)cardiac t(略)
项目受资助省
浙(略)
项目结题报告(全文)
研究背景:Apel(略)偶联受体APJ的内(略)管系统和液体的平衡(略)疾病如动脉粥样硬化(略)房颤动等的发生发展(略)也是继瘦素和脂肪细(略)谢的脂肪因子。但是(略)统在布比卡因中毒致(略)作用尚未见研究报道(略)代大鼠心肌细胞布比(略)卡因中毒心脏骤停模(略)水平,探讨Apel(略)卡因致大鼠心脏毒性(略)pyr1]Apel(略)因心脏中毒的复苏作(略)和关键数据:布比卡(略)胞后,APJ和Ap(略)于对照组(P<0.(略)1)apelin-(略)的SD大鼠心脏骤停(略)B组=100%vs(略)剂可消除外源性ap(略)A组vs FBA=(略)。B、BA组首次心(略)(P<0.05)。(略)NA seq发现a(略)粒体生物合成相关蛋(略)C-1α、ACC、(略)显著高于S、B组,(略)蛋白表达显著高于S(略)乳鼠心肌细胞搏动次(略))apelin-1(略)60min时的pA(略)CC/ACC表达量(略)调节OCR,用腺病(略)elin的保护作用(略)3可逆转布比卡因导(略)pelin可逆转布(略)室肌细胞钠通道抑制(略)果表明(Pyr1)(略)救大鼠布比卡因所致(略)因对乳鼠心肌细胞搏(略)肌细胞钠通道抑制,(略)K/ACC-调节O(略)功能,为心肌细胞的(略)
1.肾上腺素对布比卡因抑制大鼠心室肌细胞钠电流的影响
- 关键词:
- 布比卡因 肾上腺素 钠电流 心室肌细胞 大鼠 基金资助:国家自然科学基金资助项目(81470419); 浙江省科技厅国际科技合作专项(合作研究)项目(2012C24018); 温州市科技局科研基金资助项目(Y20150239); 专辑:医药卫生科技 专题:外科学 分类号:R614 手机阅读
- 陈鸿飞;刘付丽;吴一泉;徐旭仲
- 0年
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目的:研究肾上腺素对较低浓度布比卡因所抑制的大鼠心室肌细胞钠电流(INa)的影响。方法:采用急性酶解分离法获得Sprague-Dawley雄性大鼠心室肌细胞,随机分为2组(n=5),以全细胞膜片钳技术记录INa,观察0.15μg/m L肾上腺素对40μmol/L布比卡因和50μmol/L布比卡因所抑制的INa的影响。结果:40μmol/L和50μmol/L布比卡因对大鼠心室肌细胞INa抑制率分别为(50.2%±5.8%)和(62.7%±7.7%),差异有统计学意义(P<0.05)。当加入0.15μg/m L肾上腺素后,40μmol/L布比卡因组抑制率变到(33.7%±10.2%),差异有统计学意义(P<0.05);50μmol/L布比卡因组抑制率变为(62.1%±7.3%),差异无统计学意义(P>0.05),肾上腺素对I-V曲线无明显影响。结论:肾上腺素可以部分恢复较低浓度布比卡因所抑制的心室肌细胞INa,但其作用在较高浓度布比卡因中受到限制。
...2.肾上腺素对脂肪乳剂复苏布比卡因所致离体心脏停搏效果的影响
- 关键词:
- 肾上腺素 脂肪乳剂 布比卡因 心脏停搏 复苏 基金资助:国家自然科学基金资助项目(81470419); 温州市科技局资助项目(Y20150239); 专辑:医药卫生科技 专题:外科学 分类号:R614 手机阅读
- 陈鸿飞;夏芳芳;张裕坚;吴辉;徐旭仲
- 0年
- 卷
- 期
- 期刊
目的探讨肾上腺素对脂肪乳剂复苏布比卡因所致离体心脏停搏效果的影响。方法 24只雄性SD大鼠按随机数字表法分为实验组和对照组,每组12只,制作Langendorff离体心脏灌流模型,以100μmol/L布比卡因诱导心脏停搏后继续灌注3min,对照组采用含有2%脂肪乳剂和100μmol/L布比卡因的灌流液,实验组采用含有0.15μg/ml肾上腺素和2%脂肪乳剂以及100μmol/L布比卡因的灌流液。记录离体心脏首个心搏时间(Te)、复跳时间(Tr)以及复跳后1(T1)、5(T2)、10(T3)、20(T4)、30(T5)和40min(T6)的心率(HR)、左室发展压(Lvdev P)以及心率左室发展压乘积(RPP),并进行组间比较。结果实验组的Te和Tr均短于对照组(均P<0.05)。实验组HR、Lvdev P和RPP在复跳后T1T2高于对照组(均P<0.05)。复跳后T3T6,两组间心功能差异均无统计学(均P>0.05)。结论肾上腺素可以缩短脂肪乳剂解救临床浓度布比卡因所致离体心脏停搏复苏时间,并且可以增强复跳后初期(复跳后5min内)离体心脏心功能,但是对复跳后期心功能无明显作用。
...3.Levosimendan combined with epinephrine improves rescue outcomes in a rat model of lipid-based resuscitation from bupivacaine-induced cardiac arrest
- 南芙蓓;蔡茜茜;叶颖超;徐旭仲;李正迁;李明;陈丽梅;
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4.Supplement of levosimendan to epinephrine improves initial resuscitation outcomes from asphyxial cardiac arrest
- 吴冰晶;彭勇刚;赵施施;鲍娜娜;潘霖敏;董娇娇;徐旭仲;王权光;
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5.Comparative Regimens of Lipid Rescue From Bupivacaine-Induced Asystole in a Rat Model
- 《ANESTHESIA AND ANALGESIA》
- 2019年
- 128卷
- 2期
- 期刊
BACKGROUND: It is currently unknown whether bupivacaine-induced asystole is better resuscitated with lipid emulsion (LE) administered peripherally or centrally, and whether different LE regimens administered peripherally demonstrated similar effects. In this study, we compared the effects of various regimens of lipid administration in a rat model of bupivacaine-induced asystole. METHODS: Forty-five adult male Sprague-Dawley rats were subjected to bupivacaine-induced asystole and randomly divided into 3 lipid regimens groups: (1) 20% LE was administered continuously via the internal jugular vein (CV-infusion group); (2) 20% LE was administered continuously via the tail vein (PV-infusion group); and (3) 20% LE was administered as divided boluses via the tail vein (PV-bolus group). The maximum dose of LE did not exceed 10 mL center dot kg(-1). External chest compressions were administered until the return of spontaneous circulation (ROSC) or the end of a 40-minute resuscitation period. RESULTS: The survival rate, rate of ROSC, systolic blood pressure, heart rate, heart rate-blood pressure product, and coronary perfusion pressure during 2-40 minutes in the CV-infusion and PV-bolus groups were significantly higher than those in the PV-infusion group (P < .01), and the plasma total bupivacaine concentration and myocardial bupivacaine content were significantly lower (P < .05). Time to heartbeat return and time to ROSC in the CV-infusion and PV-bolus groups were significantly shorter than those in the PV-infusion group (P < .05). CONCLUSIONS: In the rat model of bupivacaine-induced asystole, a divided LE bolus regimen administered peripherally provided a better resuscitation outcome than that of a continuous LE infusion regimen peripherally, and performed in a similar fashion as the continuous LE infusion regimen administered centrally.
...6.Effect of Ultrasound-guided Nerve Block With 0.75% Ropivacaine at the Mid-forearm on the Prevalence of Moderate to Severe Pain After Hand Surgery
- 关键词:
- analgesia; mid-forearm; ultrasound-guided; wrist and hand surgery;BRACHIAL-PLEXUS BLOCK; INTERSCALENE BLOCK; MOTOR BLOCK; ANESTHESIA;ANALGESIA; ULNAR
- Bao, Nana;Chen, Limei;Xia, Yun;Wang, Quanguang;Shi, Kejian;Papadimos, Thomas J.;Xu, Xuzhong;Zhou, Riyong
- 《CLINICAL THERAPEUTICS》
- 2018年
- 40卷
- 6期
- 期刊
Purpose: This study tested the hypothesis that ultrasound-guided mid-forearm nerve block with 0.75% ropivacaine reduces the prevalence of moderate to severe pain after wrist and hand surgery, and provides prolonged postoperative analgesia with minimal motor blockade.Methods: Thirty patients undergoing elective wrist and hand surgery were randomly assigned to 1 of 2 groups: group R (n = 15) and group NS (n = 15). We combined an ultrasound-guided supraclavicular brachial plexus block with mid-forearm median, radial, and ulnar nerve block in all patients. The supraclavicular brachial plexus was blocked with 20 mL of 1.5% lidocaine, and the mid-forearm nerves were blocked with 15 mL of either 0.75% ropivacaine (group R) or normal saline (5 mL each nerve) (group NS). A blinded observer provided a numeric rating pain score at 1, 2, 6, 12, 24, and 48 hours after surgery. The durations of sensory and motor blockade, patient satisfaction, morphine requirement for postoperative pain rescue, and adverse events were recorded.Findings: The prevalence of moderate to severe pain in group R was significantly lower than that in group NS (33% vs 86%; P = 0.008). The highest mean (SD) numeric rating pain score (worst pain) in group R was lower than that in group NS (2.7 [1.9] vs 5.6 [2.9]; P = 0.004), and the median (Q1, Q3) amount of morphine required for postoperative pain rescue in group R was lower than that in group NS (0 [0, 6] vs 8 [6, 10]; P = 0.001]. Additionally, there were no differences in the durations of motor blockade between the 2 groups. (C) 2018 Elsevier HS Journals, Inc. All rights reserved.
...7.度洛西汀对大鼠心肌缺血再灌注心律失常的影响及机制
- 关键词:
- 度洛西汀;缺血再灌注损伤;室性心律失常;氧化应激
- 蔡茜茜;徐旭仲
- 《医学研究杂志》
- 2018年
- 卷
- 04期
- 期刊
目的 探讨度洛西汀对大鼠心脏缺血再灌注心律失常的影响及机制。方法 30只Sprague Dawley(SD)大鼠随机分为假手术组(Sham组)、缺血再灌注组(IR组)和度洛西汀组(Dulo组)。IR组大鼠左前降支结扎30min后再灌注120min,Dulo组大鼠结扎左前降支30min前腹腔注射盐酸度洛西汀40mg/kg,之后处理同IR组,Sham组仅暴露左前降支,未行结扎。二导联心电监测并记录3组心律失常发生情况,应用Lab Chart8软件分析心电图参数。Triphenyltetrazolium chloride(TTC)染色对比IR组及Dulo组大鼠心肌梗死面积。蛋白免疫印迹试验检测各组心脏组织Akt、细胞外调节蛋白激酶(extracellular regulated protein kinases,Erk)、caspase-3、超氧化物歧化酶(superoxide dismutase,SOD)1、SOD2和连接蛋白43(connexin 43,Cx 43)蛋白改变。结果 与IR组比较,缺血期Dulo组大鼠室性期前收缩次数和室性心动过速次数减少(P<0.05);再灌注期Dulo组的室性心动过速减少(P<0.05),室性期前收缩次数差异无统计学意义(P>0.05)。度洛西汀抑制缺血和再灌注所致校正后Q-T间期(QTc)的延长(P<0.05),并减小心肌梗死面积(P<0.05)。度洛西汀抑制Akt和Erk蛋白的磷酸化,减少cleaved caspase-3、cytochrome C蛋白表达并增加SOD1、SOD2和Cx43蛋白表达。结论 度洛西汀降低Akt和Erk蛋白磷酸化,抑制氧化应激及细胞凋亡,减低心脏缺血再灌注损伤过程中室性心律失常发生,减少梗死面积。
...8.左西孟旦对脂肪乳剂复苏布比卡因所致大鼠离体心脏停搏的影响
- 关键词:
- 左西孟旦;脂肪乳剂;布比卡因;心脏停搏;复苏
- 夏芳芳;陈鸿飞;金周晟;施克俭;陈丽梅;徐旭仲
- 《温州医科大学学报》
- 2017年
- 卷
- 07期
- 期刊
目的:研究左西孟旦对脂肪乳剂复苏布比卡因所致离体心脏停搏效应的影响。方法:16只雄性SD大鼠,随机分为2组(n=8),采用Langendorff离体心脏装置,建立离体心脏布比卡因停搏模型。对照组:以2%脂肪乳剂进行灌流;实验组:采用5μmol/L左西孟旦和2%脂肪乳剂进行灌流。观察复跳情况和复跳时间(Tr),记录复跳后40 min内心率(HR)、HR和左室发展压乘积(RPP)、左心室内压最大上升速率(+dp/dt)和冠脉流量(CF)以及心律失常情况。结果:2组离体心脏均复跳,Tr差异无统计学意义(P>0.05)。与对照组比,实验组离体心脏复跳后40 min内的心功能参数HR、RPP和+dp/dt均较高,差异有统计学意义(P<0.05);复跳后实验组中离体心脏的CF明显大于对照组,差异有统计学意义(P<0.05);2组均未出现室性心律失常。结论:在离体心脏布比卡因停搏模型上,左西孟旦有利于改善脂肪乳剂复苏后心功能和CF,不增加室性心律失常发生的风险。
...9.Epinephrine Deteriorates Pulmonary Gas Exchange in a Rat Model of Bupivacaine-Induced Cardiotoxicity A Threshold Dose of Epinephrine
- 关键词:
- LIPID-BASED RESUSCITATION; INDUCED CARDIAC-ARREST;CARDIOPULMONARY-RESUSCITATION; EMULSION; OVERDOSE; PHARMACOKINETICS;ASSOCIATION; VASOPRESSIN; COMBINATION; ANESTHESIA
- Wang, Quan-Guang;Wu, Cong;Xia, Yun;Dong, Jiao-Jiao;Lin, Ting-Ting;Liu, Qiao-Yan;Papadimos, Thomas J.;Xu, Xu-Zhong
- 《REGIONAL ANESTHESIA AND PAIN MEDICINE》
- 2017年
- 42卷
- 3期
- 期刊
Background and Objective: The study goal was to compare the effect of epinephrine in different doses on pulmonary gas exchange in a rat model of bupivacaine-induced cardiac depression.Methods: Twenty-four adult male Sprague-Dawley rats were divided into 4 groups (n = 6), and each group received a bupivacaine infusion (2.5 mg/kg per minute, 6 minutes) via the left femoral vein to induce cardiac depression. At the end of the bupivacaine infusion, each group was immediately given either isotonic sodium chloride solution (normal saline; NS group), 5-mu g/kg epinephrine (Epi5 group), 10-mu g/kg epinephrine (Epi10 group), or 20 mu g/kg epinephrine (Epi20 group). Left atrial pressures were monitored for 20 minutes after epinephrine was administered (as was the NS group). Arterial blood gas analyses were performed before bupivacaine infusion and at the end of the 20-minute monitoring period.Results: The Epi10 and Epi20 groups had lower pH (P = 0.02 and P < 0.001, respectively) and PaO2 (P = 0.049 and P < 0.001, respectively), and a higher PaCO2 (P < 0.001 and P < 0.001, respectively) compared with the NS group. There were no statistical differences between the Epi5 and NS groups in pH, PaCO2, or PaO2. Left atrial systolic pressure was higher in the Epi10 group (P = 0.002) and the Epi20 group (P < 0.001) within 2 minutes of epinephrine administration. There was no statistical difference between the Epi5 and NS groups in left atrial systolic pressure.Conclusion: A single injection of 10 mu g/kg epinephrine or greater was associated with deterioration of pulmonary gas exchange in our rat model of bupivacaine induced cardiac depression.
...10.肾上腺素复苏不同浓度布比卡因所致大鼠离体心脏停搏的效应
- 关键词:
- 肾上腺素;布比卡因;心脏停搏;复苏;线性关系;大鼠
- 陈鸿飞;蔡茜茜;夏芳芳;陈丽梅;王权光;徐旭仲
- 《温州医科大学学报》
- 2017年
- 卷
- 02期
- 期刊
目的:研究肾上腺素复苏不同浓度布比卡因所致离体心脏停搏的效应。方法:36只雄性SD大鼠,随机分为6组(n=6),建立离体心脏布比卡因停搏模型。C组:予以0.15μg/m L肾上腺素进行灌流;B10、B20、B30、B40和B50组:分别予以10、20、30、40、50μmol/L布比卡因和0.15μg/m L肾上腺素进行灌流。观察复跳后15 min内心率(HR)以及HR和左室发展压乘积(RPP)。结果:除B50组,各组均复跳。复跳后15 min内,HR和RPP比较:C组>B10组>B20组>B30组>B40组,且差异均有统计学意义(P<0.01)。复跳后RPP最大恢复率(RPPr)(y)与布比卡因浓度(x)存在线性关系,线性回归方程式为y=-2.385x+114.5,pearson相关系数r=-0.993。结论:在离体心脏水平上,肾上腺素复苏效果和布比卡因浓度呈负相关,布比卡因浓度为50μmol/L时,肾上腺素复苏效果已被限制。
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