黄连、吴茱萸药对中盐酸小檗碱在急性胃溃疡模型大鼠体内的药代动力学研究

目的比较黄连-吴茱萸药对提取液中盐酸小檗碱在急性胃溃疡模型大鼠与正常大鼠体内的药代动力学差异,探讨病理状态对盐酸小檗碱体内过程的影响。方法分别灌胃给予正常大鼠和急性胃溃疡模型大鼠黄连-吴茱萸(6:1)药对提取液,采用高效液相色谱方法测定大鼠体内盐酸小檗碱的血浆浓度,色谱柱:Diamonsil C18(150mm×4.6mm,5μm);流动相:乙腈-甲醇-0.05mol/L磷酸二氢钾溶液(23∶12∶65),流速:1.0ml/min;检测波长:345nm;柱温:30℃。结果盐酸小檗碱在正常组的药代动力学参数:Cmax=0.064±0.01μg/ml;Tmax=(0.42±0.13)h;t1/2=(5.96±1.16)h;AUC0-t=(0.42±0.08)μg/(ml.h);AUC0-∞=(0.45±0.09)μg/(ml.h)。盐酸小檗碱在模型组的药代动力学参数:Cmax=(0.069±0.01)μg/ml;Tmax=(0.54±0.11)h;t1/2=(5.11±1.78)h;AUC0-t=(0.60±0.17)μg/(ml.h);AUC0-∞=(0.63±0.18)μg/(ml.h)。结论黄连-吴茱萸药对在乙醇致急性胃溃疡模型大鼠中吸收减慢,但是吸收量多,体内滞留时间稍延长。     

吡硫醇在低氧与常氧环境下大鼠体内的药代动力学研究

目的研究比较吡硫醇在低氧和常氧状态大鼠体内的药代动力学特征。方法将SD大鼠采用数字表法随机分为低氧组与常氧组,低氧动物预处理后进行吡硫醇单次灌胃给药的药代动力学研究。采用本课题组建立的快速灵敏的超高效液相质谱联用测定不同时间的血药浓度,用DAS2.0软件计算药动学参数,并用SPSS13.0软件进行统计学分析。结果吡硫醇在常氧和低氧大鼠体内的主要药动学参数分别为:AUC_(0-t)(88.26±9.86)ng·h·mL~(-1)和(80.67±8.95)ng·h·mL~(-1);MRT_(0-t)(4.14±0.32)h和(3.67±0.26)h;t_(1/2)(3.72±1.82)h和(3.14±1.42)h;t_(max)(0.58±0.20)h和(0.67±0.26)h;C_(max)(30.12±2.36)ng/mL和(20.05±1.31)ng/mL。与常氧状态大鼠的药动学参数相比,低氧状态下吡硫醇在大鼠体内的C_(max)和MRT_(0-t)有显著性降低,而其他主要药动学参数差异均无统计学意义。结论低氧影响药物在大鼠体内达峰浓度,进而可影响药物的稳态血药浓度、治疗效果和毒性反应。     

HPLC-MS/MS测定大鼠血浆中人参皂苷Rg3的浓度

目的 建立高效液相色谱-串联质谱(HPLC-MS/MS)法测定大鼠血浆中人参皂苷Rg3的浓度,用于大鼠体内人参皂苷Rg3的药代动力学研究.方法 血浆样品经乙酸乙酯液-液提取.色谱柱为Inertsil ODS-3(2.1 mm×50 mm,5μm),流动相:乙腈:10 mmol/L乙酸铵水溶液(含0.1％甲酸,90:10);流速:0.4 mL/min;ESI离子源,负离子模式监测.6只大鼠灌胃给予人参皂苷Rg3 20 mg/kg后按预定时间点眼眶采血.采用DAS 3.3.1软件统计其药代动力学参数.结果 血浆中人参皂苷Rg3的线性范围为2 ～ 400 ng/mL,日内、日间精密度及基质效应RSD均小于15％,主要的药代动力学参数:AUC0-t为(821.659±170.125)ng·h/mL,AUC0-∞为(912.468±190.653)ng·h/mL,Cmax为(138.803±28.997) ng/mL,t1/2为(2.803±0.263)h.结论 建立的方法快速、灵敏、准确.适用于大鼠血浆中人参皂苷Rg3浓度的测定.     

黎药材海南牛耳枫大鼠体内药动学研究

目的研究大鼠灌胃给药海南牛耳枫提取物后槲皮素在大鼠体内的药物动力学特征。方法采用LC-MS/MS法,测定灌胃给药后大鼠血浆中槲皮素的浓度变化,用DAS2.0药动学软件处理,计算药动学参数。结果大鼠灌胃给药海南牛耳枫提取物后槲皮素在大鼠体内动力学参数为Tmax=（0.195±0.155）h,Cmax=（35.00±15.30）ng/ml,AUC0-t=（66.82±21.77）ng/（ml·h）,t1/2=（5.736±2.513）h。结论该法选择性强、灵敏度高,适用于药材及制剂中槲皮素的体内药动学研究。     

调经祛斑胶囊中芍药苷在大鼠体内的药代动力学研究

目的：研究调经祛斑胶囊有效成分芍药苷在大鼠体内的药代动力学特征,为临床合理用药提供参考依据。方法：采用反相高效液相色谱法（RP—HPLC）测定大鼠灌胃给予调经祛斑胶囊后不同时间血浆中芍药苷的浓度,DAs2．0药动软件计算芍药苷的药动学参数并拟合平均药物浓度-时间曲线。结果：大鼠给予调经祛斑胶囊后,芍药苷在大鼠的体内过程符合一室模型。结论：调经祛斑胶囊中芍药苷在大鼠体内消除较快。建立的血浆中芍药苷的分析方法简便、灵敏、重现性好,可用于芍药苷的药代动力学研究。     

Study on Pharmacokinetic Properties of Curcumin Derivative FM0807 in Mice under Different Drug Administration Manners

目的 研究姜黄素衍生物FM0807在不同给药方式的小鼠体内药代动力学特征. 方法 用HPLC法测定FM0807经静脉注射、灌胃给药后的小鼠血浆中FM0807及其代谢产物姜黄素的浓度,计算药代动力学参数. 结果 姜黄素在小鼠体内的代谢过程符合二室开放模型;静脉给药后的药代动力学参数为t1/2β 13.58 min、AUC 620.66 μg/(mL/min)、Vd 2.59 L/kg、Cmax 62.11μg/mL,灌胃给药后t1/2β 79.86 min、AUC 59.81 μg/(mL/min)、Vd 317.35 L/kg、Cmax 0.50 μg/mL. 结论 FM0807静脉给药迅速代谢为姜黄素,维持有效血药浓度50 min,FM0807灌胃后,姜黄素药-时曲线呈双峰,可能存在肝肠循环.     

液相色谱-串联质谱测定大鼠血浆中紫云英苷的浓度及其药代动力学研究

目的建立液相色谱-串联质谱法(LC-MS/MS)测定大鼠血浆中紫云英苷的浓度,并研究其灌胃给药后在大鼠体内的药代动力学特征。方法以槲皮素为内标,采用HPLC-MS/MS方法,色谱柱为Agilent ZORBAX SB-C18,流动相为甲醇-10 mmol/L醋酸铵水溶液-甲酸(80∶20∶0.15,v/v/v),采用多反应监测(MRM)模式,监测离子分别为:m/z 449.1→m/z287.1(紫云英苷),m/z301.1→m/z151.1(槲皮素);DAS2.0药动学软件计算药动学参数。结果紫云英苷在1.00～1000 ng/ml浓度范围内线性关系良好(r2=0.9929);定量下限为1.00 ng/ml;低、中、高浓度的提取回收率均大于93%。大鼠灌胃给药后在0.5±0.1 h达到231.1±67.3 ng/ml的峰值浓度,血浆半衰期为3.9±1.3 h,AUC0-∞为782.6±152.8(ng.h/ml)。结论本方法灵敏度高、选择性强、分析时间短,适用于血浆中紫云英苷的浓度测定及其药代动力学研究。     

雷替曲塞在大鼠血浆和脑组织中的分布研究

目的研究雷替曲塞静脉注射后在大鼠血浆和脑组织中的分布。方法采用HPLC法测定雷替曲塞2.5 mg.kg-1尾静脉注射后大鼠血浆和脑组织匀浆中的雷替曲塞浓度,计算药代动力学参数并比较评价。结果雷替曲塞在大鼠血浆及脑组织中的Tmax均为5 min,而Cmax分别为(12381.79±4515.83)ng.ml-1和(219.48±53.52)ng.ml-1,ROC曲线下面积(AUC)分别为(750 983.94±2 635.87)ng.min-1.ml-1和(962.25±147.18)ng.min-1.ml-1,血浆中Cmax和AUC显著高于脑组织中,差异具有统计学意义(P<0.01)。雷替曲塞在血浆中t1/2为(142.7±39.1)h。结论雷替曲塞静脉注射后能迅速分布到有关器官和组织,但不易透过血脑屏障。雷替曲塞在体内代谢缓慢,能较长时间维持有效的血药浓度。     

急性CCl_4肝损伤对大鼠芍药苷药代动力学的影响

目的:研究芍药苷在CCl4所致急性肝损伤大鼠中的药代动力学。方法:反相HPLC法(内标为栀子苷)测定大鼠血浆中的芍药苷浓度。用CCl4制造大鼠急性肝损伤模型。动物分对照组和实验组,给药途径为尾静脉注射,剂量为3 mg/kg。结果:在大鼠急性CCl4肝损伤模型中,芍药苷的多个药代动力学参数(除了MRT)与对照组相比,均有显著性差异。结论:肝损伤会明显改变芍药苷在大鼠体内的药动学行为,可为临床芍药苷的应用提供参考。     

环磷酰胺对丁硫氨酸亚砜胺在大鼠体内的药代动力学影响

目的研究环磷酰胺(CTX)对丁硫氨酸亚砜胺(BSO)在SD大鼠体内的药代动力学的影响. 方法 SD大鼠腹腔注射CTX 20mg/kg(用药组)或生理盐水(对照组)4d后,静脉注射BSO 200mg/kg.以邻-苯二甲醛(OPA)柱前衍生反相HPLC为检测手段,测定血浆中BSO的浓度.以3P87软件对实验数据进行拟合,判断房室模型并计算药代动力学参数. 结果 SD大鼠静脉注射BSO 200mg/kg,体内的动力学过程为二室模型,T1/2α为27.4±5.3min, T1/2β为159.3±107.3min,CLs为11.8±2.3ml*min-1*kg-1,AUC为299.36±50.13μg*ml-1*h;SD大鼠在用CTX后,BSO在其体内动力学特征也是二室模型,T1/2α为25.2±2.2min,T1/2β为114.3±25.9min,CLs为13.8±3.8ml*min-1*kg-1,AUC为256.55±66.28μg*ml-1*h.用药组和对照组的药代动力学参数无显著性差异.结论 CTX不影响BSO在大鼠体内的药代动力学过程.     

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.     

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.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

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.     

The clinicopathological and immuohistochemical analysis of solid-pseudopapillary tumor of the pancreas： report of 9 cases

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.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

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.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

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.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

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.