阿霉素纳米脂质体大鼠体内的药动学研究

目的 研究阿霉素纳米脂质体的动物体内药物动力学参数,为临床用药提供依据.方法 建立HPLC法测定血浆中的阿霉素药物浓度,测定动物体内药物动力学参数.结果 该试验采用的高效液相法具有较高的专属性,在血药浓度为0.25～25.00μg/mL范围内线性良好,有良好的相关系数(r=0.9996),回收率(RSD＜9%).阿霉素和阿霉素纳米脂质体在大鼠体内符合三室房室模型,阿霉素和阿霉素纳米脂质体的t1/2α分别为(0.031±0.012)h和(0.060±0.013)h,t1/2β分别为(2.57.±1.20)h和(5.45±0.72)h,AUC分别为(2 821.7±791.3)μg/L·h和(4012.2±804.8)μg/L·h.结论 阿霉素和阿霉素纳米脂质体均符合三室房室模型,但阿霉素纳米脂质体药时曲线下面积增大,有效作用时间延长,有利于抗肿瘤作用,降低心脏毒性.     

阿霉素纳米脂质体制备工艺研究

目的 本实验尝试制备阿霉素纳米脂质体并测定其包封率,探求其最佳制备工艺.方法 采用薄膜分散高压均质法制备阿霉素纳米脂质体,高效液相色谱法检测阿霉素包封率.结果 制得的阿霉素纳米脂质体大小均匀、分散性好、粒径在180nm左右、包封率为71.46%,4℃保存3个月稳定.阿霉素在0.54μg/mL～21.60μg/mL范围内线性良好(r=0.9997),回归方程为Y=46632x+19140.结论 该法制备的阿霉素纳米脂质体,工艺简单易行,质量可控.     

芦荟大黄素纳米脂质体介导的光动力对胃癌细胞的作用

目的：探讨芦荟大黄素纳米脂质体介导的光动力作用对胃癌细胞增殖、凋亡的影响。方法：体外培养人胃癌细胞SGC-7901,芦荟大黄素纳米脂质体（16 μg/ml）作用胃癌细胞（1、2、4、6、8 h）后,采用激光共聚焦显微镜检测芦荟大黄素纳米脂质体在胃癌细胞中的摄取情况;不同浓度芦荟大黄素纳米脂质体（0、2、4、8、16、32 μg/ml）作用胃癌细胞4 h后,不同能量紫外光处理（紫外光波长为430 nm,连续输出方式,功率密度40 mW/cm2）胃癌细胞,光能量密度分别为：0.0、0.8、1.6、3.2、6.4、12.8、25.6 J/cm2,采用MTT法检测胃癌细胞增殖率的变化;芦荟大黄素纳米脂质体（16 μg/ml）作用胃癌细胞4 h后,能量密度为（6.4 J/cm2）紫外光处理（紫外光波长为430 nm,连续输出方式,功率密度40 mW/cm2）胃癌细胞,采用Hoechst33342细胞核染色观察凋亡细胞形态学的变化;采用流式细胞仪检测胃癌细胞凋亡率的变化。结果：芦荟大黄素纳米脂质体在胃癌细胞中的吸收时间在4 h达到高峰;不同浓度芦荟大黄素纳米脂质体作用胃癌细胞4 h后,浓度低于8 μg/ml时对胃癌细胞的抑制作用差异无统计学意义（P=0.945,P=0.074）;单纯光照组与单纯芦荟大黄素纳米脂质体组对胃癌细胞抑制作用差异无统计学意义（P=0.125）;芦荟大黄素纳米脂质体（16 μg/ml）介导的光动力（6.4 J/cm2）作用胃癌细胞12 h后,胃癌细胞凋亡率芦荟大黄素纳米脂质体PDT组高于空白对照组、纳米脂质体组;Hoechst33342细胞核荧光染色可以观察到细胞核固缩、碎裂,可见凋亡小体。结论：芦荟大黄素纳米脂质体介导的光动力作用能有效的诱导胃癌细胞凋亡,芦荟大黄素纳米脂质体介导的光动力可能成为治疗胃癌的新方法。     

萝卜硫素脂质体对S-180肉瘤细胞小鼠移植瘤的抑制作用

目的 探讨萝卜硫素(SFN)脂质体的体内抗肿瘤作用并讨论其可能机制.方法 首先体外观察SFN脂质体组及游离药物组对S-180肿瘤细胞株的抑制作用,进行细胞内药动学实验.然后建立S-180肉瘤细胞小鼠皮下移植瘤动物模型,观察SFN脂质体组及游离药物组对荷瘤小鼠肿瘤生长的抑制作用,检测肿瘤中药物含量.通过Western blot检测SFN脂质体对荷瘤小鼠金属蛋白酶(MMP)-2的影响,采用一氧化氮合成酶检测试剂盒检测荷瘤小鼠的一氧化氮合成酶含量.结果 在体外实验中,SFN脂质体抑制S-180细胞的半抑制浓度(IC50)为33.1 μmol/L,小于游离SFNIC50 44.3 μmol/L.细胞内药动学参数提示,SFN脂质体进入S-180细胞内的程度较游离SFN增加.SFN脂质体低、中、高三个剂量组均能明显抑制荷S-180荷瘤小鼠的肿瘤生长,与相同剂量游离SFN(50 mg/kg)比较,脂质体的抑瘤率(44.09％)增强近一倍(24.55％),生命延长率有所增加(P＜0.01).中、高剂量的SFN脂质体明显下调小鼠肿瘤部位中的一氧化氮合成酶的表达(P＜0.01).Western blot检测结果表明,高剂量浓度的SFN脂质体用药后,明显下调小鼠瘤组织中的MMP-2蛋白的表达(P＜0.0t).结论 SFN脂质体具有较强的体内外抗肿瘤活性,作用强于游离SFN.其机制可能与实体瘤的高通透性和滞留效应、抑制基质MMP-2活性来阻止肿瘤细胞的入侵,并使得一氧化氮合成酶浓度降低减少一氧化氮分泌,从而降低血管通透性,减少肿瘤组织供应,抑制肿瘤的生长等有关.     

半乳糖化白蛋白磁性阿霉素纳米粒体对外肝癌细胞杀伤作用的实验研究

目的研究半乳糖化白蛋白磁性阿霉素纳米粒在体外对人肝癌细胞系HepG2的杀伤作用.方法应用电镜下的形态学观察,DNA电泳以及MTT法检测杀瘤活性.结果形态出现明显改变,电镜证实出现细胞凋亡;白蛋白磁性阿霉素纳米粒联合磁场(MADM-NP M)组和半乳糖化白蛋白阿霉素纳米粒(Gal-ADM-NP)组抑制率及半数抑制率剂量相似(P＞0.05),半乳糖化白蛋白磁性阿霉素纳米粒(Gal-MADM-NP M)组抑制率明显提高,半数抑制剂量明显降低(P＜0.01).结论实验结果表明,白蛋白磁性阿霉素纳米粒联合磁场、半乳糖化白蛋白阿霉素纳米粒、半乳糖化白蛋白磁性阿霉素纳米粒都具有明显抑制体外培养肝癌细胞生长增殖的作用.半乳糖化白蛋白磁性阿霉素纳米粒对人肝癌细胞杀伤作用较白蛋白磁性阿霉素纳米粒及半乳糖化白蛋白阿霉素纳米粒组为强,作用机制可能与半乳糖配体的特异性介导和人肝癌细胞上半乳糖受体的识别内吞作用及联合外磁场有关.     

青蒿琥酯纳米脂质体抗人肝癌HepG2细胞作用研究

目的:将青蒿琥酯纳米脂质体与青蒿琥酯原料药对比,研究其体外抗肝癌作用.方法:应用青蒿琥酯纳米脂质体和原料药作用HepG2细胞,MTT法检测对细胞的增殖抑制作用;用hoechst 33258染色法观察细胞凋亡的形态学改变.应用RT-PCR检测细胞凋亡因子caspas-3表达.结果:青蒿琥酯纳米脂质体及原料药抗肝癌作用呈浓...     

阿霉素纳米脂质体的制备及安全性评价

目的 制备阿霉素纳米脂质体,并研究其急性毒性和慢性毒性.方法 通过乙醇注入法结合pH梯度法,制备阿霉素纳米脂质体,并通过粒径仪测定其物理化学性质.阿霉素纳米脂质体的长期毒性和慢性毒性则通过昆明小鼠实验进行评价.结果 通过该方法制备的阿霉素纳米脂质体粒径为140～170 nm,包封率高达99.85％.急性毒性实验表明,阿霉素纳米脂质体的LD50为31.69mg/kg,病理结果提示,阿霉素纳米脂质体在0mg/kg和6mg/kg的剂量下未对小鼠各脏器产生明显的毒性;12mg/kg及以上剂量,对小鼠心、肺及肝组织都有一定的毒性,且与剂量大小相关;18mg/kg及更低的剂量下,未见其对小鼠肾脾组织有明显毒性.慢性毒性实验中,与空白对照组比较,6 mg/kg和9mg/kg剂量组小鼠体质量、RBC压积、平均RBC体积、PLT计数和嗜酸性粒细胞百分数及尿素氮含量(BUN)有显著影响(P＜0.05).结论 该方法制备的阿霉素纳米脂质体质量稳定,且对动物的毒性具有剂量依赖性.     

CMCT-FA修饰阿霉素纳米脂质体的制备与体外pH敏感释放

利用1乙基3(3二甲基丙基)碳二亚胺 (EDC)介导反应合成了叶酸偶联的羧甲基壳聚糖（CMCTFA）,以阿霉素为模型药物,采用薄膜分散pH梯度法制备CMCTFA修饰的阿霉素纳米脂质体。考察了CMCTFA修饰阿霉素纳米脂质体的包封率、粒径、ζ电位以及在不同pH释药介质中的释放特性。结果表明：CMCTFA修饰阿霉素纳米脂质体的ζ电位较未修饰脂质体明显减小,但较CMCT修饰阿霉素纳米脂质体无明显差别;与阿霉素纳米脂质体和CMCT修饰的阿霉素纳米脂质体相比,CMCTFA修饰的阿霉素纳米脂质体在酸性条件下的药物释放速率和药物释放量均有明显提高。     

王浆酸锗对U14瘤的抑制作用

目的 观察王浆酸锗体内外对小鼠U14瘤的抑制作用。方法 MTT法评价王浆酸锗体外抑制U14瘤的活性;建立小鼠U14瘤模型,以王浆酸锗高、中、低剂量连续给药10d,分离瘤体,计算肿瘤抑制率,评价其体内抗肿瘤活性。结果 MTT法显示王浆酸锗(1 mg/L, 10 mg/L and 100 mg/L)体外对U14瘤的抑制率分别为18.43%, 33.12% 和 55.20%,IC50为43.60 mg/L;体内活性实验表明王浆酸锗高、中剂量组和低剂量组的抑制率分别为70.0%, 51.8% 和 42.4%。结论 王浆酸锗对小鼠U14瘤有较强的抑制作用。     

开口箭皂甙抑制小鼠S-180肉瘤细胞增殖及实体瘤生长的实验研究

目的 研究开口箭皂甙(STCB)体内外抗S-180肉瘤活性的强度及其作用机制.方法 MTT法检测S-180细胞的增殖程度;制备昆明种小鼠S-180移植实体瘤模型,观察STCB的抑瘤作用;光镜和电镜下观察药物作用后S-180细胞形态及超微结构变化;以不同浓度STCB处理S-180细胞,经碘化丙啶染色后应用流式细胞术检测细胞周期及细胞凋亡情况.结果 STCB体外明显抑制S-180细胞增殖,IC50为34.64μg/ml.经灌胃给药,STCB对荷S-180实体瘤小鼠表现出良好的抑瘤作用,低剂量(0.5 g/kg体质量)时,抑瘤率已超过30%,高剂量(2 g/kg体质量)时,抑制率达到54.86%.电镜观察和FCM检测证明肿瘤细胞凋亡率随STCB浓度增加而增加.STCB的浓度为10和30μg/ml时,S期细胞百分率上升,G2/M期细胞百分率下降;当STCB的浓度达到60μg/ml,G0/G1期细胞百分率下降,G2/M期细胞百分率上升:提示低浓度STCB阻止S-180细胞从S期进入G2期;高浓度时,STCB还干扰S-180细胞的有丝分裂.结论 STCB在体内外对S-180肉瘤细胞均有抑制作用,其作用机制与诱导肿瘤细胞的凋亡和干扰细胞周期有关.     

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…     

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.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.     

Luo Lingjie's Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.     

Dr.Zhang Ren's Experience in the Acupuncture Treatment of Different Diseases with the Same Therapeutic Principle

Dr.Zhang Ren,the chief physician,is the chairman of Shanghai Acupuncture and Moxibustion Association.Having been engaged in medicine for about 40 years,he is experienced in treating various intractable diseases.In his long years of clinical practice,he advocates taking the TCM differentiation as the basis to seek for the acupuncture method for treatment of modern intractable diseases.The author of this essay had the fortune to follow Dr.Zhang in study.The following is a summary of Dr.Zhang's experience in the acupuncture treatment for different intractable diseases with the same therapeutic principle.     

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.     

猪肺磷脂注射液联合经鼻持续气道正压通气对呼吸衰竭早产儿的临床疗效及肌酸激酶同工酶活性的影响

目的 探讨猪肺磷脂注射液联合经鼻持续气道正压通气(NCPAP)对呼吸衰竭早产儿的临床疗效及肌酸激酶同工酶活性(CK-MB)的影响.方法 选取呼吸衰竭早产儿80例,分为观察组和对照组各40例.对照组采用NCPAP给氧治疗,观察组给予NCPAP给氧联合猪肺磷脂气管内给药.观察两组患儿治疗前及治疗12h、24 h后PaO2、PaCO2、血氧饱和度(SaO2)、pH的变化情况,检测治疗前及治疗5d后血清CK-MB水平;评估两组患儿的临床治疗效果.结果 两组患儿PaO2、PaCO2、SaO2、pH比较,差异均有统计学意义(P＜0.05),其中观察组治疗后的PaO2、SaO2、pH均高于对照组,PaCO2则低于对照组.两组的PaO2、SaO2、pH均随观察时间延长而升高(P＜0.05),PaCO2均随观察时间的延长而降低(P＜0.05).观察组治疗有效率为87.5％,显著高于对照组的70.0％ (P ＜0.05).治疗5d后两组患儿血清CK-MB水平均较前降低(P＜0.05),且观察组明显低于对照组(P＜0.05).结论 猪肺磷脂注射液气管内给药联合NCPAP可以显著降低呼吸衰竭早产儿CK-MB的含量,提高治疗有效率,起到很好的呼吸循环支持作用.