卵磷脂胆固醇酰基转移酶基因单核苷酸多态性与冠心病脂代谢易感性的关联研究

目的：检测卵磷脂胆固醇酰基转移酶（lecithin cholesterol acyltransferase,LCAT）基因3个编码区单核苷酸多态位点在中国人群中的分布频率，并初步探讨它们与脂代谢和冠状动脉粥样硬化性心脏病（coronary atherosclerotic heart disease,CHD）易感性的关系。方法：采用聚合酶链反应－限制性片段长度多态性方法，分析209名正常人和203例CHD患者中608C／T、911T／C和1188C／T（参照序列：NM_000229）3个位点的多态性。结果：608C和608T等位基因频率分布符合Hardy-Weinberg平衡。CHD患者组608T频率显著低于正常人群（P＝0．034）。与无608T CHD患者相比，具有608T的CHD患者的血浆高密度脂蛋白胆固醇显著升高（P＝0．015）。911T／C和1188C/T在两组中均未检出。结论：LCAT基因608T等位基因与CHD患者较高的血浆高密度脂蛋白胆固醇水平相关联，可能与中国人CHD相关。911T／C和1188C／T在中国人群中非常罕见。     

脂质体空气微泡的制备

采用薄膜水化法,以卵磷脂、胆固醇以及聚乙二醇作为膜材制备包封空气的脂质体微泡,微泡平均直径2.54μm,99%微泡大小分布在1～5μm,微泡浓度为2×108个/mL,脂质体包封空气含量为7.01μL/mL。实验研究了超声功率与超声时间,磷酸盐缓冲溶液pH值,以及糖溶液和聚乙二醇对微泡体系的影响。     

Topical Delivery of Flurbiprofen from Pluronic Lecithin Organogel

The purpose of this research is to formulate and evaluate the suitability of pluronic lecithin organogels containing flurbiprofen for topical application. Four formulations were developed using flurbiprofen, lecithin, Pluronic F127, isopropyl palmitate, water, sorbic acid and potassium sorbate were coded as FL1, FL2, FL3 and FL4. All the formulations carried 30% w/w of lecithin phase and 70% w/w of Pluronic phase. The formulated organogels were evaluated for appearance and feel psychorheologically, in vitro diffusion study, drug content, viscosity and pH. Release of flurbiprofen from all formulations was monitored via dialysis membrane-70 and Wistar rat skin as a semipermeable membrane into phosphate buffer saline (0.2 M, pH 7.4) using Keshary-Chien diffusion cell. The viscosities of different formulations were determined by using Brookfield Viscometer at 25°. An attempt has been made to explore the potential of pluronic lecithin organogels for topical delivery of flurbiprofen.     

Plasma lecithin: cholesterol acyltransferase activity in liver disease

Abstract. In liver disease the proportion of plasma cholesterol present in the form of ester is lower than that found in normal subjects. Recent work has suggested that a plasma enzyme, lecithin: cholesterol acyltransferase (LCAT), may be a major f actorin the physiological regulation of plasma cholesterol ester levels. In patients with a variety of hepatobiliary disorders LCAT activity was found to be reduced and a study of the effects of interaction between normal and jaundiced plasmas supported the hypothesis that the low LCAT activity was due mainly to a reduction in the plasma concentration of the enzyme. When bile salts were added to an in vitro system clear evidence of inhibition of LCAT was produced only with concentrations higher than those normally found in the plasma of patients with liver disease. This casts doubt on the suggested role of bile salts as in vivo inhibitors of the enzyme. The cholesterol ester concentration of plasma showed good correlation with its LCAT activity when this was measured in a standard substrate. Our results suggest that reduction in LCAT activity may be an important factor in the production of the low ester: free ratio found in almost all hepatic disorders.     

Interaction of milk-thistle-fruit flavanonols with Langmuir monolayers of lecithin and bilayers of liposomes

Interactions of silybin and dihydroquercetin (taxifolin), flavanonols from milk thistle [Silybum marianum (L.) Gaertn.] fruits, with Langmuir monolayers of lecithin and bilayers of liposomes are compared. It is established that the investigated flavanonols have different mechanisms of action. Taxifolin produces predominantly membrane-stabilizing action whereas silybin is characterized by immobilization in the hydrophobic part of the phospholipid bilayer with the formation of more hydrophilic micellar structures. The presence of silybin and taxifolin in the liquid extract of milk thistle fruits suggests that a dual mechanism of action may occur in this preparation and also in other combined medicines based on these fruits. The results of this study show good prospects for creating combined preparations based on milk thistle fruit, taxifolin, and other flavonoids (quercetin, rutin, diosmin, etc.) possessing pronounced membrane-stabilizing action. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 43, No. 2, pp. 33–42, February, 2009.     

Rate‐limiting factors of cholesterol efflux in reverse cholesterol transport: Acceptors and donors

1. Plasma levels of high‐density lipoprotein (HDL) are believed to be inversely related to coronary artery disease. High‐density lipoprotein plays a key role in the process of reverse cholesterol transport, by which HDL is able to extract excess cholesterol from peripheral tissues and transfer it to the liver for biliary excretion. 2. Efflux of lipids (cholesterol and phospholipids) is the first step in reverse cholesterol transport. Several cellular membrane transporters, including ABCA1 and ABCG1, as well as scavenger receptor (SR)‐BI receptor, are believed to facilitate the active efflux of cholesterol to lipid‐poor apolipoprotein A‐I and mature HDL, respectively. Furthermore, overexpression or deletion of one or more specific genes supports the view that HDL is involved in cholesterol efflux. 3. In conclusion, current evidence supports a critical role for HDL in atheroprotection via an active efflux pathway through reverse cholesterol transport, with the substantial support of appropriate functions of cell donors.     

盐酸小檗碱脂质体制备工艺研究

目的用薄膜蒸发法制备盐酸小檗碱脂质体。方法用离子交换树脂法测定脂质体包封率。以盐酸小檗碱脂质体包封率为指标,考察脂质体包封率的影响因素。结果制备盐酸小檗碱脂质体的最佳工艺条件为孵化温度65℃,孵化时间40min;此时包封率最高,且随着卵磷脂浓度的变化而变化。结论薄膜蒸发法制备的盐酸小檗碱脂质体粒径小、包封率高,条件易掌握,故该法可作为盐酸小檗碱脂质体的常规制备方法。