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1.
目的测评地卓西平(MK-801)对大鼠吗啡位置偏爱及戒断体征的影响,探讨NMDA受体在吗啡依赖中的作用.方法51只雄性Sprague-Dawle大鼠随机等分为对照组、吗啡组和干预组.吗啡组大鼠每天两次腹腔注射吗啡(剂量渐增,10天);干预组大鼠于每次注射吗啡前30min腹腔注射MK-801(0.075 mg/kg);对照组接受相同的试验操作.结果与对照组相比,吗啡组大鼠建模后停留于自侧的时间明显延长(P<0.05),戒断第1d、3d戒断体征总分显著升高(P<0.01);干预组大鼠与对照组差异不显著(P>0.05).与吗啡组相比,干预组大鼠停留于白侧的时间在建模第5d、9d明显减少(P<0.01),戒断第1d、3d的戒断总评分显著减低(P<0.01).结论MK-801抑制了吗啡诱导的条件性位置偏爱及大部分吗啡戒断体征.表明谷胺酸NMDA受体在阿片精神及躯体依赖中均有重要作用.  相似文献   

2.
目的 谷氨酸NMDA受体拮抗剂地卓西平(MK801)对大鼠急性吗啡依赖戒断性情绪反应的影响.方法 以条件性位置厌恶(CPA)实验建立急性吗啡依赖大鼠戒断性情绪反应模型,观察大鼠训练前后在"纳络酮匹配侧"停留时间的变化.结果 吗啡(5.6mg.kg-1)纳络酮(0.5 mg.kg-1)间隔4h皮下注射,进行2轮纳络酮匹配训练,能建立稳定的急性吗啡依赖戒断诱发的CPA模型;注射纳络酮前30min分别注射生理盐水和不同剂量的MK801(0.05 mg.kg-1;0.1 mg.kg-1),3组大鼠在"纳络酮匹配侧"停留时间训练前、后分别是[(447.25±47.99)s vs(238.00±20.56)s];[(454.63±44.04)s vs(395.38±55.95)s];[(450.38±51.37)s vs(419.63±52.88)s],Post Hoc Tests表明只有空白对照组的训练前后差异显著,而MK801干预的2组训练前后并无显著差异.对急性吗啡依赖和未接触吗啡的大鼠注射MK801,4组大鼠在"处理侧"停留时间训练前后组间和组内均无显著差异,即该剂量的MK801不具有奖赏效应.结论 MK801阻断了CPA的获得可能是直接抑制戒断时厌恶性情绪反应而非其本身具有奖赏效应,提示谷氨酸NMDA受体是介导急性吗啡依赖戒断性情绪反应的部分神经机制.  相似文献   

3.
目的:观察烫伤应激后海马糖皮质激素受体(GR)基因表达的变化,探讨N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)受体在这种变化中的作用。方法:利用RT-PCR技术,检测烫伤前腹腔注射NMDA受体拮抗剂MK-801及激动剂NMDA对烫伤应激后2h GR mRNA水平的影响。结果:烫伤应激后2h海马GR mRNA水平明显降低(P<0.01);应激前腹腔注射MK-801使烫伤后降低的GR mRNA水平明显恢复(P<0.01),注射NMDA使其进一步降低(P<0.05),注射生理盐水无明显变化。结论:NMDA受体介导了烫伤应激导致的海马GR转录水平基因表达的下降。  相似文献   

4.
吗啡成瘾时脑细胞凋亡数目增加   总被引:1,自引:0,他引:1  
目的 观察吗啡成瘾大鼠脑细胞凋亡数目的变化.方法 将24只体重为190~210 g的成年Sprague-Dawley大鼠随机分为吗啡依赖组、吗啡戒断组和对照组,每组8只.依据药物递增原则,吗啡依赖组和吗啡戒断组大鼠腹腔内注射吗啡13d,建立吗啡成瘾模型.吗啡戒断组大鼠在成瘾后予腹腔内注射纳洛酮5 mg/kg,诱导戒断30 min.对照组大鼠在相同的治疗时间予腹腔内注射0.9%氯化钠溶液.应用脱氧核苷酸末端转移酶介导的生物素化dUTP缺口末端标记技术(TUNEL)检测细胞凋亡,采用免疫组织化学方法检测Caspase-3蛋白表达情况.结果 吗啡依赖组的戒断症状评分与对照组的差异无统计学意义(P>0.05),但显著低于吗啡戒断组(P<0.01),表明吗啡成瘾模型建立成功.吗啡依赖组和吗啡戒断组的大鼠海马区脑细胞凋亡百分率均显著高于对照组(P值均<0.01),吗啡依赖组与吗啡戒断组间的差异无统计学意义(P>0.05).吗啡依赖组和吗啡戒断组的大鼠海马区脑细胞内Caspase-3蛋白表达阳性细胞百分率均显著高于对照组(P值均<0.01),吗啡依赖组与吗啡戒断组间的差异无统计学意义(P>0.05).结论 长期应用吗啡可诱发大鼠脑细胞异常凋亡,这可能是阿片类药物引起脑内神经改变的机制之一.  相似文献   

5.
目的 探讨脊髓水平N-甲基-D-天冬氨酸受体(N-methyl-D-aspartic acid receptor,NMDAR)-细胞外信号调节蛋白激酶5(extracellular signal-regulated kinase 5,ERK5)信号通路在吗啡依赖大鼠戒断行为中的作用.方法 成年雄性SD大鼠96只,体质量200~ 250 g,采用随机数字法,将实验动物随机分为四组(n=24):对照组(A组)、戒断组(B组)、二甲基亚砜(DMSO)组(C组)、MK801组(D组).采用剂量递增法皮下注射吗啡以建立大鼠吗啡依赖模型,第6天上午经腹腔注射纳洛酮,催促戒断症状出现,即建立吗啡戒断模型.采用行为药理学方法结合western blot技术,鞘内注射NMDAR抑制剂MK801,观察其对吗啡依赖大鼠戒断行为、戒断所致痛觉过敏及脊髓p-ERK5表达的影响.结果 A组大鼠腹腔注射纳洛酮后并未出现戒断症状及痛觉过敏.与A组相比,B组大鼠戒断症状评分[(45.2±7.3)分]、痛觉过敏评分[(14.4±3.7)分],C组大鼠戒断症状评分[(44.7±6.2)分]、痛觉过敏评分[(13.2±2.7)分],D组大鼠戒断症状评分[(28.3±1.6)分]、痛觉过敏评分[(5.9±11)分]明显增加(P<0.05);与C组相比,D组大鼠鞘内注射MK801后戒断症状评分[(28.3±1.6)分]、痛觉过敏评分[(5.9±1.1)分]明显降低(P<0.05).与A组相比,B组大鼠脊髓水平p-ERK5(12 848±621)、C组大鼠脊髓水平p-ERK5(12 579±396)表达显著上调(P<0.05);与C组大鼠脊髓水平p-ERK5(12 579±396)相比,D组大鼠鞘内注射MK801后脊髓水平p-ERK5(5123±546)表达显著下调(P<0.05).结论 脊髓水平NMDAR-ERK5信号通路参与吗啡依赖大鼠戒断症状的表达.  相似文献   

6.
目的 探讨盐酸戊乙奎醚(PHC)对吗啡依赖大鼠戒断症状及条件性位置偏爱效应的影响.方法 (1)48只雄性SD大鼠,随机分为吗啡依赖组(MOR组),纳洛酮促戒断组(NAL组),PHC治疗组(PHCl,2,3组),对照组(NS组),每组8只.剂量递增法连续5 d皮下注射吗啡(10~50mg/kg,每日2次)及纳洛酮催促戒断(5 mg/kg),建立吗啡躯体依赖大鼠模型.实验第6天上午,纳络酮催促戒断前30min腹腔注射不同剂量的PHC(0.5,1.0,1.5 mg/kg).观察各组大鼠在20 min内的体质量丧失情况及戒断症状.(2)40只雄性SD大鼠,随机分为吗啡诱导组(MOR组),PHC治疗组(PHC1,2,3组),对照组(NS组),每组8只.连续7d交替皮下注射吗啡(10mg/kg,每天1次)或生理盐水,诱导大鼠的吗啡位置偏爱效应.实验第8天停用吗啡,NS组与MOR组腹腔注射等体积的生理盐水;PHC治疗组则分别腹腔注射PHC 0.5,1.0,1.5 mg/kg.各组大鼠行CPP测试.结果 (1)PHC治疗组能明显缓解吗啡依赖大鼠的催促戒断症状,其体质量丧失[(8.53±1.20)g、(7.36±1.06)g、(5.40±1.79)g,(12.63±2.22)g,F=83.16,P<0.01]和戒断症状评分[(25.36±3.11)分、(21.38±3.50)分、(17.06±1.78)分,(31.69±2.76)分,F=256.56,P<0.01)]明显低于NAL组,且呈剂量依赖性.(2)PHC治疗组的灰区停留时间与MOR组比较显著缩短[(529±83)s、(460±107)s、(418±97)s,(643±111)s,F=13.22,P<0.01],且呈剂量依赖性.结论 PHC急性治疗能剂量依赖的抑制吗啡依赖大鼠戒断症状和条件性位置偏爱的表达.  相似文献   

7.
Cedemex对吗啡依赖大鼠戒断症状的干预及治疗作用   总被引:4,自引:0,他引:4  
目的:观察草药制剂Cedemex对吗啡依赖大鼠催促戒断症状的干预及治疗作用.方法:用7 d时间建立吗啡依赖大鼠模型,末次注射吗啡后,给大鼠灌胃不同剂量的Cedemex,分别在4 h及治疗5 d后腹腔注射纳洛酮进行催促戒断,记录1 h内戒断症状评分值及体重变化.结果:Cedemex高、低剂量组吗啡依赖大鼠经纳洛酮催促出现的戒断症状均显著减轻(P<0.05),同时能对抗吗啡依赖大鼠体重的下降.结论:Cedemex对吗啡依赖大鼠催促戒断症状有明显的干预作用和治疗作用.  相似文献   

8.
吗啡依赖和戒断大鼠脊髓内NA能神经元变化的研究   总被引:4,自引:0,他引:4  
目的探讨慢性吗啡处理及戒断后大鼠脊髓内NA能神经元的形态变化.方法24只雄性SD大鼠随机分为吗啡依赖组、吗啡戒断组和生理盐水对照组,每组8只.依赖组大鼠以腹腔注射吗啡方法建立吗啡依赖模型.戒断组大鼠在依赖模型建立后于腹腔注射纳洛酮5 mg/kg诱导戒断症状,对照组大鼠注射等量生理盐水.注射24 h后取脑和脊髓作冰冻切片.利用免疫组化方法检测各组大鼠脊髓及LC内NA能神经元的变化.结果正常组LC内DBH阳性细胞数为(98±17),吗啡依赖组和戒断组LC内DBH阳性细胞数分别为(212±20)和(229±27),明显高于正常组(P<0.01),但平均灰度值无明显差异.慢性吗啡处理后脊髓前角DBH阳性神经元数量增多,染色加深,后角和侧角新增加大量阳性神经元,吗啡依赖组和戒断组DBH阳性神经元增加具有极显著意义(P<0.01).结论慢性吗啡处理和戒断引起LC和脊髓内NA能神经元增多,提示NA与吗啡依赖和戒断的形成有关,其可能是吗啡依赖及戒断的分子机制之一.  相似文献   

9.
王惠玲  赵晏  向晓辉  王会生 《医学争鸣》2004,25(16):1448-1451
目的:研究中脑一边缘多巴胺回路腹侧被盖区(VTA)内源性谷氨酸信号转导在吗啡戒断形成中的作用.方法:给VTA微注射不同剂量谷氨酸NMDA受体拮抗剂( )MK-801,用行为学方法观察对吗啡戒断大鼠戒断症状的影响.递增量吗啡ip7d建立依赖模型,末次给药1.5hip盐酸纳洛酮(2mg/kg)诱发戒断症状,以Gellert-Hohzman Score和湿狗样颤为评价戒断症状程度的指标,进行统计学分析.结果:( )MK-801(2,5,10g/L)微注射于VTA可明显减弱吗啡戒断大鼠湿狗样颤的发生次数,且能显著降低吗啡戒断鼠的Gellert-Holtzman Score.结论:VTA内源性谷氨酸受体及其与中脑一边缘多巴胺能信号转导相互作用,参与吗啡戒断的形成,提示谷氨酸受体拮抗剂可用于吗啡戒断的治疗。  相似文献   

10.
目的 观察吗啡成瘾时脑细胞中凋亡相关蛋白Fas、Caspase-3和Bcl-2表达的改变.方法 将48只体质量为190~210 g的成年SD大鼠随机分为3组:吗啡依赖组、吗啡戒断组和对照组,每组16只.依据药物递增原则,依赖组和戒断组大鼠腹腔内给予吗啡13d,建立吗啡成瘾模型.戒断组大鼠在成瘾后腹腔内注射纳洛酮5 mg/kg,诱导戒断30 min.对照组大鼠在相同的治疗时间腹腔内注射生理盐水.应用免疫组织化学、蛋白印迹分析方法检测大鼠海马区Fas、Bcl-2和Caspase-3蛋白的表达.结果 与对照组比较,吗啡依赖组和戒断组大鼠海马区Fas和Caspase-3的表达增加(P<0.01),而Bcl-2的表达降低(P<0.01).结论 长期应用吗啡可通过Fas、Caspase-3表达的增加和Bcl-2表达的降低诱发脑细胞异常凋亡,这可能是阿片类药物引起神经损害的机制之一.  相似文献   

11.
Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P < 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (>0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P <0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P < 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.  相似文献   

12.
Objective: To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods: SD rats served as both donors and recipients. 4℃ sodium lactate Ringer's was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava (IVC) inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results: Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion: This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.  相似文献   

13.
Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P< 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P< 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.  相似文献   

14.
目的:评价使用安心颗粒对急诊经皮冠状动脉介入术(PPCI)术后生活质量的影响.方法:将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组(术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次)和对照组(仅接受基础药物治疗).所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表(MIDAS)、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果:入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异(P>0.05);出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低(P<0.05);组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低(P<0.05).两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血(P>0.05).两组发生轻度血小板减少症的患者数比较无差异(P>0.05).结论:PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.  相似文献   

15.
Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P<0.01);the MAP decreased(P<0.01)and the HR increased drastically(P<0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.  相似文献   

16.
Objective:To investigate the gene expression of osteoprotegerin(OPG) and osteoclast differentiation factor(ODF) in the bone tissue of patients with hip fracture due to osteoporosis. Methods:OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers(over 50 years old) with hip fracture(Observer Group) and 30 cases of hip facture sufferers with no osteoporosis(Control group) were analyzed with the Semi-Quantitative RT-PCR method. Results:The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion:Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.  相似文献   

17.
Objective:To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas(SPTP). Methods:Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin(HE) staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results:Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin(9/9 cases), AAT(9/9 cases), NSE(9/9 cases), ACT(7/9 cases), CK20(2/9 cases), CgA(1/9 cases), S-100(3/gcases), PR(4/gcases), Syn(3/9 cases) and CD56(5/9cases), negative in CEA and ER. Conclusion:SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.  相似文献   

18.
Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.  相似文献   

19.
Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.  相似文献   

20.
Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.  相似文献   

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