脂质体导向给药治疗缺血性心脏病的可行性研究(Ⅰ)

本工作在离体大鼠心肌细胞、离体灌流大鼠和家兔心脏模型上,对脂质体作为药物载体导向治疗缺血性心脏病的可行性进行了基础研究。结果表明,心肌细胞可通过融合(Fusion)、内吞(Endocytosis)、吸附(Adsorption)和磷脂分子交换(Exchange)四种方式与脂质体相互作用。细胞摄取脂质体的方式主要取决于脂质体的理化性质。缺氧改变了心肌细胞对脂质体的摄取方式并增加其摄取能力。缺血心肌组织对脂质体、尤其对带正电荷脂质体的摄取显著增加。其摄取量按序为缺血-再灌注区>梗塞边缘区>非缺血区>梗塞区。上述实验结果提示:脂质体作为药物载体可将药物输送到缺血心肌组织和心肌细胞内。     

Role of Regulatory Peptide in Pathogenesis of Shock

The present study evaluated the pathogenetic roles of three kinds of regulatory peptide. The results showed that (i) plasma endothelin(ET) level elevated significantly in septic shock rats, persistent intravenous drip of low doses ET caused development of shock state in normal rats and the irreversible outcome of light hemorrhagic shock. Furthermore, i. v. administration of specific ET-antiserum was significantly effective to septic shock rats, (Ⅱ) Plasma calcitonin gene-related peptide (CGRP) increased by 260% in septic shock rats, i. v. drip of low doses CGRP both in early and late sepsis were effective to shock rats, (Ⅱi) An-giotensin-Ⅱ (ANG-Ⅱ) contents of heart and aorta increased dramatically both in early and late septic shock, and inhibiting its increase with Captopril in late sepsis significantly improved the shock state, but results were inverse in early sepsis. It could be concluded that ET was one of the most important factors participating in the pathogenesis of shock, CGRP had a compens     

脂质体导向给药治疗缺血性心脏病的可行性研究(Ⅱ)

在离体大鼠心脏灌流模型上,发现用高[Ca~(2+)](4.5mmol/L)、高[K~+](8.7mmol/L)或自由基发生系统灌流,显著增加心肌对脂质体的摄取。静脉注射与大鼠心肌细胞抗体共价结合的脂质体,显著增强了脂质体趋心肌组织的靶向性。用脂质体携载超氧化物歧化酶(superoxide dismutase,SOD)治疗大鼠心肌缺血-再灌注损伤,其疗效远优于单用SOD治疗。实验结果表明,脂质体作为药物载体治疗缺血性心脏病可能具有临床应用前景。     

氯化亚铈对大鼠血液动力学的影响

稀土元素对心血管功能的影响,国内尚未见报道。国外虽有报道,但定量的整体研究不多。我国某些轻稀土矿区,居民头发中稀土含量较高,并伴有心脏不适、肢体无力的反映。一些稀土生产厂,接触轻稀土粉尘的工人,有心率过缓现象。故有必要探讨摄入过多稀土时,对心血管系统的影响。为此,我们进行了氯化亚铈急性静脉注射和亚急性喂     

一氧化氮样舒张因子在休克中的变化及意义

本工作观察了大鼠止血带休克、败血症休克和小肠缺血再灌注休克一氧化氮样舒张因子(NO-LRF)的变化及作用。结果表明,休克动物离体主动脉对去甲肾上腺素的反应降低,组织cGMP含量增加。NO合成前体L-精氨酸(L-Arg)或NO合成阻断剂L-硝基精氨酸(L-NNA)、可溶性鸟苷酸环化酶抑制剂亚甲基蓝(MB)分别增强或减弱休克动物主动脉的上述变化,且这些药物的作用不依赖于血管内皮的存在,提示休克时非内皮源的NO-LRF生成增多是血管对收缩物质反应性降低的原因之一。整体实验发现,L-NNA加重晚期休克动物的低血压并恶化预后,而L-Arg延缓休克动物的血压降低,减轻组织损伤,提示NO-LRF对机体有重要的保护作用,休克时非内皮源NO-LRF生成增多可能是机体的适应性代偿反应。     

溶剂热条件对MIL-53(Fe)结晶度及吸附性能的影响

采用溶剂热法制备一系列金属有机骨架材料MIL-53(Fe),使用傅立叶变换红外光谱仪、X射线衍射仪、电子扫描电镜等表征手段对其结构进行表征.探讨了其对有机染料亚甲基蓝的吸附性能.通过改变反应温度来调控MIL-53(Fe)的结晶度,结果表明,高结晶度的MIL-53(Fe)更利于吸附行为.吸附动力学、等温线研究表明,该吸附过程符合准二级动力学和Langmuir等温线模型.     

Possibility of Targeting Treatment for Ischemic Heart Disease With Liposome (Ⅰ)

This paper reports the basic research on the possibility of using targeting treatment for ischemic heart disease with liposome as drug carrier. Studies have been performed on isolated rat cardiomyocytes, or isolated perfused rat and rabbit hearts. Results show that cardiomyocytes may interact with liposome through fusion, endocytosis, adsorption and molecular exchange of phospholipid. Forms of cellular uptake of liposome depend chiefly on the physicochemical properties of liposomes. Anoxia changes the pattern of liposome uptake by cardiomyocytes and increases uptake of liposomes. Uptake of liposomes, especially of positively charged liposomes by ischemic myocardium is significantly increased. The quantity of increase of liposome uptake is in the following order: ischemia-reperfusion area>peripheral area of the infarct>non-ischemic area>infarcted area. The above results indicate that liposome as drug carrier might promote the delivery of drug into ischemic myocardium and cardiomyocytes.     

ROLE OF Na~+-Ca~(2+) EXCHANGE SYSTEM IN THE PATHOGENESIS OF MYOCARDIAL ISCHEMIA-REPERFUSION DAMAGE

Results from a systematic experiment on isolated perfused rat heart and isolated myc-cytes of adult rat showed that the mechanism of calcium influx during myocardial ischemia-reperfusion is due to the development of intracellular sodium overload during ischemic pe-riod, on reperfusion, the high intracellular Na~+ content activated the reverse direction ofNa~+-Ca~(2+) exchange over myocardial sarcolemma (SL), thus a large quantity of extracellularCa~(2+) fluxed over the SL to the intracellular space, forming a condition of intracellular Ca~(2+)overload, which leads to irreversible damage of the myocardium.     

Na~+-Ca~(2+)交换机制在心肌缺血-再灌注损伤中的发病学意义

本工作在大鼠的离体灌流心脏和分离的成年大鼠心肌细胞上进行了系统实验,结果表明心肌缺血-再灌注时细胞外钙离子内流的主要机制在于缺血期细胞内钠离子超负荷,激活了心肌质膜上Na~+-Ca~(2+)交换的反向运转,从而使细胞外大量Ca~(2+)内流,形成细胞内Ca~(2+)超负荷,后者导致心肌的不可逆损伤。     

在心脏和血管平滑肌中心钠素钙拮抗作用

在离体及在体心脏和血管平滑肌上,系统研究了心钠素(ANP)的钙拮抗作用。培养的兔血管平滑肌细胞实验结果表明,ANP明显抑制细胞的钙内流,对内皮素(ET)和高钙刺激引发的钙内流也有抑制。ANP可明显减轻离体大鼠心脏缺钙-复钙引起钙超载(钙反常)所致心肌损伤和抑制维生素D_3加尼古丁所致大鼠心肌和血管钙超载,改善钙超载引起的血管舒缩功能障碍。对ET升血压和缩血管效应有明显拮抗效应。