维拉帕米对链脲佐菌素诱导糖尿病大鼠心肌缺血再灌注损伤的影响及机制

目的 观察维拉帕米(Ver)对糖尿病大鼠心肌缺血再灌注(L/R)后心功能,细胞内[Ca2+]i及L-型钙电流(ICa-L)影响,探讨其防治糖尿病心肌I/R损伤的作用和机制.方法 链脲佐菌素诱导糖尿病大鼠后的第6～14周龄给予Ver(8 mg·kg-1·d-1)灌胃,Langendorff系统复制大鼠心肌I/R模型,观察不同实验组的心功能变化,双酶法急性分离各组心肌细胞,激光扫描共聚焦显微镜加Fluo-3/AM荧光染色技术和全细胞膜片钳技术分别观察心肌细胞内Ca2+荧光强度和ICa-L大小.结果 (1)与糖尿病组相比,Ver糖尿病组的左心室发展压(91.3±4.6)mm Hg(1 mm Hg=0.133kPa)、舒张末压(1535±280)mm Hg、收缩压最大上升速率(5833±256)mm Hg/s、冠状动脉流量(13.7±0.9)ml/min均明显增加(P<0.01),收缩压最大下降速率(3504±319)mm Hg/s明显减少(P<0.01).(2)Ver糖尿病组心肌细胞内Ca2+荧光强度(155.6±10.9)nmol/L与糖尿病组(245.2±17.5)nmoL/L相比明显减弱(P<0.01).(3)当指令电位为+20 mV时,Ver糖尿病组心肌细胞ICa-L为(-6.81±0.76)pA/pF,与正常对照组[(-8.17±2.07)pA/pF]相比减小(P<0.05),与糖尿病组[(-3.21±0.54)pA/pF]相比增加(P<0.01),与Ver对照组[(-7.14±2.17)pA/pF]相比减少(P>0.05).Ver糖尿病组的I-V曲线显著低于糖尿病组,最大峰值在+20 mV.结论 Ver可以明显改善I/R损伤引起的糖尿病大鼠心功能下降,其机制可能是Ver调控心肌细胞膜上ICa-L内流大小,优化心肌细胞内[Ca2+]i平衡,避免I/R时心肌细胞内Ca2+超载.     

S-亚硝基谷胱甘肽对PGF2α诱导心肌肥大的抑制作用

目的 从细胞水平研究一氧化氮(Nitric oxide,NO)供体S-亚硝基谷胱甘肽(S-nitrosoglutathione,GSNO)对前列腺素F2α(PGF2α)所致心肌肥大的影响,并初步探讨其作用原理.方法 利用培养的新生大鼠心肌细胞,以细胞直径大小、蛋白质含量为心肌肥大反应指标,观察药物的抗心肌肥大效应;分别用比色法和荧光法检测细胞NO浓度和游离钙浓度([Ca2+]i),分析其可能的作用原理.结果 PGF2α10-7mol/L使心肌细胞明显增大,蛋白质含量明显增加,并使[Ca2+]i显著升高,但对NO含量无明显影响.与PGF2α组比较,GSNO10-4mol/L明显使心肌细胞直径、蛋白质含量和[Ca2+]i减少;同时使NO浓度明显增加,差异有统计学意义(P<0.05).结论 GSNO可抑制PGF2α诱导的心肌细胞肥大,该作用可能与其释放NO,使心肌细胞局部NO含量增加,从而降低细胞内钙有关.     

M_3受体激动剂胆碱对大鼠心肌细胞内钙离子的影响

目的研究M3受体激动剂胆碱对大鼠心肌细胞内钙离子的影响。方法采用钙荧光染料Fluo-3/AM负载心肌细胞,在激光扫描共聚焦显微镜(LSCM)上测定细胞[Ca2+]i的变化。结果胆碱不影响静息状态下的细胞[Ca2+]i,对咖啡因和三磷酸肌醇(IP3)介导的细胞内钙的释放均无作用。5.0 mmol/L胆碱可以抑制KCl除极诱导的心肌[Ca2+]i的升高幅度,2.0 nmol/L 4-DAMP可以阻断这一作用。结论 M3受体激动剂胆碱通过阻断心肌细胞膜电压依赖性钙通道降低心肌细胞[Ca2+]i,从而发挥心肌保护作用。     

M3 受体激动剂对慢性心衰大鼠心肌ICa-L及[Ca2+]i的影响

目的 研究M3 受体激动剂胆碱( choline)对慢性心力衰竭( CHF)大鼠心肌的保护作用及可能的机制. 方法CHF大鼠Ⅱ型胶原酶消化分离单个心肌细胞,全细胞膜片钳技术记录L-型钙电流( ICa-L )变化;激光扫描共聚焦技术观测细胞内钙([Ca2+]i)变化. 结果 膜片钳实验结果显示,与CHF组比较,choline组ICa-L电流密度明显增高( n=6,P<0. 01);预敷U73122后加入choline,与choline组比较, ICa-L电流密度明显下降(n=6,P<0. 01). 共聚焦实验结果显示,与CHF组比较,choline组[ Ca2+] i 明显升高( n=80,P<0. 01);与 choline 组比较,U73122 与 choline 共同孵育组[Ca2+]i 升高幅度不明显(n=80, P<0. 01). 预先给予4-DAMP可部分逆转choline升高ICa-L及[ Ca2+] i 的作用. 结论 M3 受体对CHF大鼠的心肌保护作用可能是通过Gq/11-PLC途径开放L-型钙通道,促进Ca2+内流,使[ Ca2+] i 增加.     

异丙酚对氯化钾和咖啡因诱发豚鼠耳蜗外毛细胞钙离子移动的影响

目的:评价异丙酚对氯化钾和咖啡因诱发豚鼠耳蜗外毛细胞钙离子移动的影响,探讨其对听觉外周感受器(耳蜗)的作用。方法:急性分离豚鼠耳蜗外毛细胞,选择30个活力较高的外毛细胞,随机分为3组(n=10):对照组(C组)、30μmol/L异丙酚组(P1组)和100μmol/L异丙酚组(P2组)。用Fluo-3AM钙荧光指示剂染色后,P1组和P2组分别给予30、100μmol/L异丙酚或咖啡因处理5min,然后加入氯化钾,采用激光共聚焦显微镜测定细胞内荧光强度的峰值,反映细胞内游离钙离子浓度([Ca2+]i)的变化。结果:异丙酚可抑制氯化钾诱发的[Ca2+]i增加并与浓度呈正相关,而对咖啡因诱发的[Ca2+]i增加无明显影响。结论:异丙酚可抑制豚鼠耳蜗外毛细胞Ca2+跨膜内流,降低[Ca2+]i,而对内质网功能无明显影响。     

Amiloride预防性给药对压力超负荷心肌肥厚大鼠左室肥厚形成及心肌细胞内游离钙的影响

采用压力超负荷心肌肥厚模型,以Fura-2/AM作为荧光指示剂,观察Amiloride(Ami)和Enalapril(Ena)预防性给药对压力超负荷左室肥厚(IVH)大鼠心肌肥厚的形成及心肌细胞[Ca2+]i的影响.结果表明,压力超负荷时,左心室重与体重之比(LVWW/BW)明显增加(P<0.01),左室心肌细胞内确有钙超载现象;Ami和Ena组的LVWW/BW较IVH组明显降低(P<0.01),左室心肌细胞[Ca2+]i亦明显降低(P<0.01).给予KCl 40 mmol·L-1、NE 20μmo1*L-1,预防给药组左室心肌细胞[Ca2+]i的增加值明显低于LVH组.     

参三七皂苷Rb1对缺氧复氧损伤心肌细胞[Ca2+]i含量和钙稳态的影响

目的:探讨参三七皂苷Rb1预处理对肥厚心肌细胞缺氧/复氧(H/R)损伤游离钙([Ca2+]i)的影响及其与心肌细胞保护作用与关系。方法:采用体外培养乳鼠心肌细胞,血管紧张素I(IAngII)刺激形成肥厚模型,实验分为7组:①正常对照组(C);②肥厚细胞模型对照组;③肥厚细胞H/R损伤组(H+H/R);④-⑦:Rb1预处理(0.01～10μmol/L)+H/R组;用激光共聚焦显微镜测定[Ca2+]i以及对电压依赖和受体操纵性激动剂KCl,NE诱发细胞内钙离子变化的影响。结果:经缺氧2h复氧1h后,肥厚细胞H/R组[Ca2+]i荧光强度较对照组显著增高,Rb1预处理组细胞内[Ca2+]i荧光强度较肥厚细胞H/R损伤组显著降低(P<0.01)。Rb1预处理使KCl、NE诱发的细胞内钙荧光强度仅增加61.3%和78.9%,升幅显著下降(P<0.01)。结论:参三七皂苷Rb1预处理具有显著减轻H/R肥厚心肌细胞钙超载作用,是其细胞保护作用的重要机制。     

辛伐他汀对血管紧张素Ⅱ诱导的乳鼠心肌细胞肥大的保护作用及机制研究

目的 探讨辛伐他汀(simvastatin,Sim)对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的心肌细胞肥大的保护作用及机制.方法 采用原代培养新生SD大鼠心肌细胞,以AngⅡ诱导心肌细胞肥大,观察Sim和环孢素A(cyclosporine A,CSA)对心肌肥厚的影响.应用计算机图像分析系统检测心肌细胞体积;考马斯亮蓝法测心肌细胞总蛋白;Till阳离子测定系统(德国)采用DM3000软件测定胞内[Ca2+]i瞬间变化;Western blotting法检测心肌细胞中钙调神经磷酸酶(calcineurin,CaN)蛋白的含量.结果 与AngⅡ组相比,Sim可以抑制AngⅡ诱导的细胞体积和总蛋白的增加(P＜0.05),抑制心肌细胞内钙离子浓度([Ca2+]i)瞬间变化幅度(P＜0.05),抑制CaN蛋白表达;Sim组与CsA(CaN抑制剂)组相比差异均无统计学意义.结论 Sim抑制AngⅡ诱导的心肌肥厚可能通过调节Ca2+/CaN通路发挥作用.     

NGF和CgA对RWPE-1细胞内钙离子浓度变化的影响及其在慢性前列腺炎中的作用

目的 探讨神经生长因子(NGF)和嗜铬颗粒蛋白A(CgA)处理后前列腺上皮细胞系RWPE-1细胞内钙离子浓度([Ca2+]i)的差异及NGF和CgA在慢性前列腺炎(CP)发病中的作用.方法 不同浓度的NGF和CgA(50、200 ng/ml)刺激RWPE-1细胞,用激光共聚焦显微镜观察不同浓度的NGF和CgA刺激后细胞内[Ca2+]i变化,加入TRPV1受体拮抗剂后继续观察细胞内[Ca2+]i变化.然后,将正常细胞外液换成D-PBS,再加入NGF和CgA观察细胞内[Ca2+]i变化.结果 50 ng/ml NGF和CgA刺激细胞后,细胞内[Ca2+]i未见明显变化.200 ng/ml NGF和CgA刺激细胞后,细胞内[Ca2+]i明显增加,加入TRPV1受体拮抗剂后,细胞内[Ca2+]i未见明显变化.将正常细胞外液换成D-PBS,用NGF和CgA刺激后,细胞内[Ca2+]i未见明显改变.结论CP的发生可能是通过分泌和释放NGF和CgA,引起前列腺上皮细胞膜TRPV1通道开放,促使细胞内钙离子浓度增加,导致前列腺上皮分泌功能下降所致.     

益气温阳活血方对慢性心衰大鼠心室重构钙调磷酸神经酶信号通路的影响研究

目的 探讨中药复方益气温阳活血方对慢性心衰大鼠心室重构钙调磷酸神经酶(CaN)信号通路的影响.方法 体内、外试验应用Fura-2/AM比率荧光成像系统检测心肌细胞内钙离子浓度([Ca2+]i);以RT-PCR法以及Western-blot法检测CaN、活化T细胞核因子3(NFAT3)mRNA及蛋白质表达水平在益气温阳活血方及拆方治疗前后的变化.结果 与正常组比较,模型组[Ca2+] i、心肌组织及心肌细胞CaN、NFAT3mRNA及蛋白质的表达水平均明显明显升高;益气温阳活血方能够明显减少[Ca2+] i、抑制CaN、NFAT3 mR-NA及蛋白质表达水平的升高.结论 CaN信号通路在慢性心衰心室重构机制中起重要作用;益气温阳活血方可能通过抑制CaN信号通路改善心室重构.     

Value of D-Dimers in patients with acute aortic dissection

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.     

Research of combined liver-kidney transplantation model in rats

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.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

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.     

Development on Adjustable Calibration Marker for Shock Wave Focus

Shock wave lithotripsy （SWL） is a treatment of choice for upper urinary stones. However, this procedure is inappropriate for obese patients because the focus is often unable to reach the target owing to the limited focal distance in shock wave source. Although treating such patients in a blast path may increase the application length of shock wave source, it＇s difficult to find this path on the lithotripter monitor. For this reason, we invented an adjustable calibration marker in order to set an effective focus in the shock wave hath.     

Study on the TCM Pathogenesis of Angiopathic Complications of Type II Diabetes

Excess production of reactive oxygen species(ROS)of mitochondrion mediated by hyperglycemia is the common pathogenesis of angiopathic complications of diabetes.TCM holds that the damp from the dysfunction of spleen.kidney and liver is the causative factor of complications of diabetes.This is similar to the mechanism of Ros resulting in angiopathic complications of diabetes.When the angiopathic complications of type II diabetes mellitus(T2DM)are difierentiated as caused by turbid damp in TCM can be explained as ROS.Since the obstruction of pathogenic damp in channels and collaterals is said to be the main pathogenesis,the treating principle should be dissolving the damp to remove the obstruction.     

Leptin, Ghrelin and TNF-α before and after Hypo-caloric Traditional Chinese Diet and Auricular Acupuncture

INTRODUCTION Obesity is a complex emergent problem, which can be possibly solved not only by the diet but also by the life style and promotion of a constant physical exercise. 1, 2 No doubt careful attentions must be given to the nutritional condition of obese people, the dietary habits, the somatic build (i.e. distribution of fat mass) and the organic functions linked to formation of the fat mass. All the parameters should be constantly monitored before, during and after a diet treatment. 3, 4, 5     

Relationship between Dysglycemia and Carotid Atherosclerosis in Tibetan Population

People with dysglycemia are at high risk for atherosclerotic diseases. This study aims at investigating the atherosclerotic vascular damage in dysglycemia and its metabolic origin in Tibetan population.     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

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.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

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.