甘草酸脂质体的制备及小鼠体内肝靶向效率的评价

目的 制备甘草酸脂质体,评价其在小鼠肝脏中的靶向性。方法 以薄膜分散-超声法制备甘草酸脂质体,于小鼠尾静脉给药,RP-HPLC法测定肝脏和血液中不同时间的药物浓度。以甘草酸注射剂为对照,通过相对摄取率(re)、靶向效率(te )和峰浓度比(Ce )3个参数来评价脂质体的肝靶向效率。 结果 甘草酸脂质体肝脏相对摄取率re=1.4;甘草酸脂质体肝靶向效率te =0.092;甘草酸注射液te =0.059,肝脏中Ce=1.59,血液中Ce=0.99。结论：与甘草酸注射剂相比,甘草酸脂质体有明显的肝靶向性。     

具有肝靶向功能的半乳糖化紫杉醇长循环纳米脂质体抑瘤作用研究

目的 构建靶向肝癌的紫杉醇长循环纳米脂质体,改善紫杉醇的体内分布,提高其安全性和抑瘤作用.方法 以新型半乳糖化胆固醇,(5-胆甾烯-3β-氧基)4-氧代-4- [2-乳糖酰胺基乙氨基]丁酸酯(CHS-ED-LA)为肝靶向辅料,采用硫酸铵梯度法制备紫杉醇普通脂质体和半乳糖化脂质体,并测定其包封率和物理性状.构建肝癌细胞HepG2的荷瘤裸鼠模型,分别尾静脉注射紫杉醇注射液(商品名为泰素)、紫杉醇普通脂质体和半乳糖化脂质体,分析它们在体内的药代动力学、组织分布及抑瘤作用.另外,分别将昆明小鼠尾静脉注射秦素、紫杉醇普通脂质体和半乳糖化脂质体,观察各药物的最大耐受量(MTD).结果 成功构建主动靶向肝癌组织的紫杉醇长循环纳米脂质体,包封率为92％以上,透射电子显微镜下观察其外观摹本呈圆整状且均匀分散,紫杉醇普通脂质体和半乳糖化脂质体的粒径分别为(78.5±27.8) nm和(88.6±32.5) nm.药物动力学结果表明,紫杉醇脂质体剂型相比泰素有较好的长循环作用,且紫杉醇普通脂质体和半乳糖化脂质体的药代动力学参数无明显差异.组织分布检测显示,半乳糖化脂质体的肿瘤组织靶向效率较紫杉醇普通脂质体及泰素均有提高,而其他器官中药物分布相对降低.紫杉醇脂质体2个剂型的最大耐受量均高于泰素.体内抑瘤实验结果显示,以相同的紫杉醇剂量给药,半乳糖化脂质体相比紫杉醇普通脂质体及泰素,其抑瘤作用更明显(P＜0.05);且半乳糖化脂质体以低剂量给药或延长给药间隔,均能达到优于紫杉醇普通脂质体及泰素的抑瘤作用.结论 本研究构建的靶向肝癌的紫杉醇长循环纳米脂质体能改善紫杉酵传统剂型的药物动力学和组织分布,提高了紫杉醇在体内的安全性和抑瘤作用.     

无唾液酸胎球蛋白修饰脂质体在小鼠体内的肝实质细胞靶向性研究

目的：研究经无唾液酸胎球蛋白（asialofetui n, AF）修饰后,脂质体达到小鼠肝实质细胞靶向的可能性。方法：用放射性同位素标记的方法测定普通长循环脂质体（ster ically stabilized liposomes, SSL）、AF-修饰普通脂质体（AF-linked normal liposomes, AF-NL）及AF-修饰长循环脂质体（AF-linked st erically stabilized liposomes, AF-SSL）在小鼠血、心、肝、脾、肺、肾等各器官及肝内不同细胞中的分布。结果：SSL、AF-NL及AF-SSL的血中半衰期分别为14.44、4.73、 11.49 h;整个肝中的分布AF-NL>AF-SSL>SSL,经 t 化极差 q 法检验,三者之间差异均存在显著性;肝不同细胞(即实质与非实质细胞)中脂质体的浓度均为AF-NL>AF-SSL>SSL（ P <0.05）,但实质细胞与非实质细胞的浓度比为AF-NL≈AF-SSLSSL（ P <0.05）。结论：经AF修饰后,无论是否长循环,脂质体均能达到很好的肝实质细胞靶向。     

RDG修饰共载多烯紫杉醇和苏拉明脂质体乳腺癌靶向治疗研究

目的探讨RDG修饰共载多烯紫杉醇(DOC)和苏拉明(Su)脂质体(RDGLP-DOC/Su)对乳腺癌的靶向治疗价值。方法采用薄膜分散法制备RDGLP-DOC/Su,并同时制备RGD修饰苏拉明脂质体(RGDLP-Su)、RGD修饰多烯紫杉醇脂质体(RGDLP-DOC),采用MMT法检测HUVEC细胞和MCF-7细胞在不同脂质体中的增殖,采用流式细胞术检测不同脂质体中细胞的摄取量。结果 RGDLP中肿瘤细胞摄取量明显高于普通脂质体(P<0.05);RGDLPDOC/Su对于乳腺癌细胞MCF-7、HUVEC的增殖抑制具有交互作用,明显高于RGDLP-Su、RGDLP-DOC(P<0.05)。结论 RGDLP-DOC/Su可有效抑制乳腺肿瘤生长和细胞增殖,具有较强的靶向治疗效果,可作为今后肿瘤靶向治疗的研究方向。     

紫杉醇脂质体腹腔给药对S180腹水瘤小鼠的疗效

目的:比较紫杉醇脂质体与紫杉醇注射液对S180腹水瘤小鼠的肿瘤抑制效果.方法:采用逆向蒸发法及超声法制备紫杉醇脂质体,以激光粒度散射仪测定粒径,以反向高效液相法测定脂质体中紫杉醇药物含量.采用S180细胞昆明鼠腹腔内注射形成腹水瘤模型,肿瘤种植24 h后随机分成4组,分别为空白对照组、空白脂质体组、紫杉醇注射液组、紫杉醇脂质体组.每组5只,其中两组分别以紫杉醇脂质体和紫杉醇注射液腹腔注射,其他2组分别给予生理盐水和空白脂质体腹腔注射,共给药4次,给药间隔72 h.结果:紫杉醇脂质体平均粒径为(282.40±8.94)nm,药物包封率为91%.肿瘤种植14天后,空白对照组、空白脂质体组、紫杉醇注射液组小鼠形成大量腹水,腹膜、肝脏广泛转移;紫杉醇脂质体组仅形成少量腹水,腹膜、肝脏未见转移.结论:紫杉醇脂质体腹腔内给药可以明显抑制腹水形成,有效抑制腹腔转移.     

乳糖脂修饰苦参碱脂质体的肝靶向性和体外抑瘤作用研究

目的:制备乳糖酰磷脂酰乙醇胺修饰的苦参碱脂质体(Lactosaminated matrine liposomes,LML),考察其在小鼠体内的肝靶向性,并研究其对人肝癌细胞系HepG2细胞的体外抑制作用.方法:采用逆向蒸发-短时超声法制备苦参碱脂质体Matrineliposomes,ML),合成乳糖酰磷脂酰乙醇胺并用其修饰苦参碱脂质体得到乳糖脂苦参碱脂质体.考察其包封率及粒径,应用反相高效液相色谱法测定小鼠体内各组织中的苦参碱含量,通过MTT法检测LML对人肝癌细胞系HepG2的体外抑制作用.结果:LML形态均匀,粒径分布范围为80～150 nm,包封率为48.1%.与苦参碱溶液(Matrine solution,M-sol)相比,普通苦参碱脂质体及乳糖脂苦参碱脂质体的体内循环时间明显延长,且乳糖脂苦参碱脂质体的肝脏药-时曲线下面积(Area undercurve,AUC)值相对于苦参碱脂质体和苦参碱溶液具有显著性差异(P<0.05) . LML组中的肝脏相对于其它脏器的靶向效率(Targeting effi-ciency,Te)值均大于1,是脾脏的2.7倍,是肺脏的3倍,是肾脏的6.6倍,是心脏的8.5倍,具有显著性差异(P<0.01)>MTT法分析发现,当浓度为0.5 mg/ml时,LML、ML及M-sol对人肝癌HepG2细胞的杀伤率分别为51.97%、31.89%和28.34%,前一组与后两组之间有显著差异(P<0.05).结论:本研究制备的乳糖脂苦参碱脂质体具有较好的体内肝靶向性和体外抑瘤作用,有望成为一种新型靶向抗肝癌药物.     

脂质体导向给药治疗心脑血管疾病的实验研究（Ⅰ）

为提高心脑血管药物的靶向性，本工作应用脂质体作为药物载体，将具有脑组织趋向性的甘露糖，血小板膜纤维蛋白原受体配基ＲＧＤＳ肽和β受体配基烯丙洛尔参入脂质体膜中，制备成靶向脂质体，在动物模型上观察靶向脂质体在组织中的分布。结果发现甘露糖脂质体携载的ＣＧＲＰ比单纯注射的ＣＧＲＰ在脑脊液和脑组织中的含量明显增加（Ｐ＜０．０５或０．０１）。ＲＧＤＳ脂质体在血栓部位的分布比非ＲＧＤＳ脂质体的分布增加１７．５倍，肝脏组织摄取量减少７倍。烯丙洛尔脂质体主要分布于β受体丰富的组织器官心脏和肺脏。结果提示应用受体配基作为归巢装置参入脂质体可以提高脂质体的组织器官靶向性。     

替加氟温度敏感性脂质体家兔体内动力学

目的:研究替加氟温度敏感性脂质体在家兔体内的动力学特点。方法:家兔静注替加氟温度敏感性脂质体,用微波电疗仪对肝脏局部加热至(42±0.1)℃,测定血中药物浓度变化,观察其体内动力学特点。结果:替加氟温度敏感性脂质体肝脏局部加热后,促进了药物在肝脏局部的释放,改变了其动力学特性,提高了替加氟温度敏感性脂质体的靶向性。结论:替加氟温度敏感性脂质体配合肝脏局部加热可提高其靶向性。     

紫杉醇阳离子壳聚糖胶束的制备及其在小鼠体内的组织分布

目的：制备紫杉醇阳离子壳聚糖胶束（PIX-CCM），研究其在小鼠体内的组织分布并进行靶向性评价。方法：采用透析法制备紫杉醇阳离子壳聚糖胶束。昆明种小鼠分别尾静脉注射20mg/kg的紫杉醇阳离子壳聚糖胶束和紫杉醇注射液，HPLC法测定各组织中不同时间的药物量，以各组织药动学参数（AUC、MRT）和靶向参数（Re、Ce、Te）为靶向评价指标。结果：PTX-CCM粒径约为164．2nm，Zeta电位为＋23．7mv，载药量为26．40％，包封率为76．23％。以紫杉醇市售注射液为对照，紫杉醇阳离子壳聚糖胶束肝、脾、肺分布增加，AUC提高分别提高5．65、91．20和2．53倍，MRT分别延长1．83、8．40和1．16倍，相对摄取率（Re）、峰浓度比（Ce）均远大于1，靶向效率（Te）均远高于对照组，而心脏和肾脏的分布显著降低，AUC分别为对照组的61．00％和89．07％，cmax为对照组的52．62％和52．94％。结论：紫杉醇阳离子壳聚糖胶束具有优良的载药性能，相对于紫杉醇市售注射液，紫杉醇阳离子壳聚糖胶束肝、脾、肺靶向性大大提高，有利于该组织的肿瘤治疗，并可显著降低紫杉醇的心脏和肾脏毒性。     

LHRHa靶向紫杉醇脂质体的制备及体外抗肿瘤作用

目的:制备促黄体激素释放激素类似物(Luteinizing hormone-releasing hormone analogues,LHRHa)靶向紫杉醇脂质体(Paclitaxel liposomes,PTX-Lipo),研究其在体外增强紫杉醇(Paclitaxel,PTX)对卵巢癌A2780/DDP细胞的抑制作用。方法:采用薄膜超声法制备PTX-Lipo与LHRHa靶向紫杉醇脂质体(LHRHa-Paclitaxel liposomes,LHRHa-PTX-Lipo),用透射电镜考察脂质体形态;高效液相色谱法测定2种PTX-Lipo的包封率;激光共聚焦法通过卵巢癌A2780/DDP细胞对4-氟-7-硝基-2,1,3-苯并氧杂恶二唑荧光素的摄取检测来反映细胞对NBD-Lipo与NBD-LHRHa-Lipo的摄取情况;MTT法及细胞克隆形成实验检测LHRHa-PTX-Lipo体外对卵巢癌细胞的生长抑制情况。结果:制备LHRHa-PTX-Lipo的平均粒径123.4 nm,包封率在90%以上;A2780/DDP细胞对NBD-LHRHa-Lipo组的荧光摄取明显高于NBD-Lipo组;LHRHa-PTX-Lipo对A2780/DDP细胞的生长及克隆形成抑制明显高于PTX组及PTX-Lipo组(P<0.05)。结论:采用薄膜超声法制备的LHRHa-PTX-Lipo可使药物在靶部位聚集,增强药物对卵巢癌细胞的抑制作用。     

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.     

CLINICAL SIGNIFICANCE OF SERUM CYTOKINES IL-1β,sIL-2R,IL-6,TNF-α,AND IFN-v IN ACUTE CORONARY SYNDROME

Objectives To explore serum cytokines levels (including IL-1 β, sIL-2R, IL-6, TNF-α, and IFN-v) and their significance in patients with acute coronary syndrome (ACS) and the subsequent follow-ups, with attempt to estimate the role of various serum inflammatory markers in the diagnosis and assessment of ACS.Methods The study population include 40 patients with acute myocardial infarction (AMI), 40 patients with unstable angina pectoris (UAP), and 40 controls. Among the 80 patients, 60 patients attended a follow up 4 months later. Serum inflammatory markers including IL-1 β, sIL-2R, IL-6, TNF-α, and IFN-v were measured by enzyme linked immunosorbent assay.Results Serum IL- 1 β, sIL-2R, IL-6, TNF-α were significantly higher in AMI group or UAP group compared to the control group and became significantly lower 4 months later in the follow-up patients. Serum levels of IFN-v shows no significant difference between AMI group or UAP group and controls, also showing no significant change when measured in follow up patients. There was no correlation between serum creatine kinase-MB isoenzyme levels and serum inflammatory markers either in UAP or AMI group. Furthermore, when divided into two subgroups using Wagner's QRS scoring system in the AMI group, there is no difference of each serum inflammatory marker between ≤ 6 scores group and ＞ 6 scores group.Conclusion Serum levels of certain inflammatory markers may have some diagnostic value for ACS, and can be a useful marker reflecting disease stability.