左旋班布特罗在动物及人体内降脂效果的研究
发布时间：2018-07-27 10:29
【摘要】：背景:高血脂症的发病率很高,可导致多种心脑血管疾病,而目前临床上的降脂药物仍无法达到预期治疗目标,研究新的降脂药物对于控制高血脂症十分有必要。左旋班布特罗(R-bambuterol,R-BMB)是班布特罗(bambuterol,BMB)的左旋异构体,具有比BMB更好的成药性且安全性十分良好,而BMB具有改善血脂的功效。因此,考察R-BMB是否具有更好的降血脂效果十分有意义。由此,我们对R-BMB在小鼠、家兔和人体内降血脂的效果进行了评价,为R-BMB作为一种降脂药提供实验基础。目的:考察R-BMB在动物体和人体内降脂效果,初步推测R-BMB降血脂的作用过程和可能的机制。方法:(1)建立Apo E-/-小鼠高血脂模型,灌胃给予R-BMB,测定小鼠不同时间点血脂水平。(2)通过高胆固醇喂养,建立家兔高血脂模型,给予R-BMB并测定家兔在不同时间点血脂的水平。(3)在随机开放的I期临床实验中,测定血浆中胆固醇及相关脂蛋白的水平,结合关键药代动力学参数,分析健康受试者口服不同剂量R-BMB后血脂下降情况。结果:(1)在给予R-BMB后,Apo E-/-小鼠体内血脂无显著性变化;(2)在进行高脂喂养后,家兔体内血脂水平(TC、LDL-C、HDL-C)显著升高,成功建立高血脂家兔模型。在给予R-BMB后,高血脂模型家兔血浆TC和LDL-C显著性下降(P0.05),而TG和HDL-C水平无显著性变化(P0.05)。(3)口服不同剂量R-BMB后,临床受试者LDL-C和TC水平显著性下降(P0.05),且具有剂量相关性,HDL-C在短期出现下降,但多次给药后恢复到给药前的水平。R-BMB对血脂的降低效果高于BMB。结论:在Apo E-/-小鼠内,R-BMB无明显降脂效果。而在家兔体内,R-BMB可显著降低LDL-C和TC水平。在人体内,R-BMB可降低血浆LDL-C和TC水平,其中对LDL-C的降低效果最为明显,且具有剂量相关性。本试验中,R-BMB对TG水平无显著性影响。R-BMB具有比Rac-BMB更好的降脂前景。
[Abstract]:Background: the incidence of hyperlipidemia is very high, which can lead to a variety of cardiovascular and cerebrovascular diseases. R-BMB is a levoisomer of bambuterolol (BMB), which has better drug formation and better safety than BMB, while BMB has the effect of improving blood lipid. Therefore, it is very meaningful to investigate whether R-BMB has better effect of lowering blood lipid. Therefore, we evaluated the effect of R-BMB on blood lipids in mice, rabbits and human beings, and provided the experimental basis for R-BMB as a lipid lowering drug. Aim: to investigate the effect of R-BMB on lowering blood lipid in animals and human body, and to speculate the mechanism and mechanism of R-BMB. Methods: (1) the hyperlipidemia model of Apo E-r-mice was established, and R-BMBs were administered intragastrically. (2) the hyperlipidemia model of rabbits was established by high cholesterol feeding. R-BMB was given to rabbits and blood lipids were measured at different time points. (3) in a randomized phase I clinical trial, the plasma cholesterol and related lipoproteins were measured, and the key pharmacokinetic parameters were combined. To analyze the decline of blood lipids in healthy subjects after oral administration of different doses of R-BMB. Results: (1) there was no significant change of blood lipid in Apo E-r-mice after R-BMB administration, and (2) after hyperlipidemia feeding, the level of serum lipids (TCU LDL-C) in rabbits was significantly increased, and the hyperlipidemia rabbit model was successfully established. After administration of R-BMB, plasma TC and LDL-C decreased significantly in hyperlipidemia model rabbits (P0.05), while TG and HDL-C levels did not change significantly (P0.05). (3) after taking different doses of R-BMB. The levels of LDL-C and TC decreased significantly in clinical subjects (P0.05), and HDL-C decreased in a short period of time, but returned to the level before administration. R-BMB was more effective than BMB in reducing blood lipids. Conclusion: R-BMB has no effect on lipid reduction in Apo-E-r-mice. However, R-BMB significantly decreased the levels of LDL-C and TC in rabbits. R-BMB can reduce plasma LDL-C and TC levels in human body. The effect of R-BMB on the decrease of LDL-C is the most obvious, and it has a dose-dependent effect. In this experiment, R-BMB has no significant effect on TG level. R-BMB has a better lipid lowering prospect than Rac-BMB.
【学位授予单位】：华南理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R589.2
本文编号：2147534
[Abstract]:Background: the incidence of hyperlipidemia is very high, which can lead to a variety of cardiovascular and cerebrovascular diseases. R-BMB is a levoisomer of bambuterolol (BMB), which has better drug formation and better safety than BMB, while BMB has the effect of improving blood lipid. Therefore, it is very meaningful to investigate whether R-BMB has better effect of lowering blood lipid. Therefore, we evaluated the effect of R-BMB on blood lipids in mice, rabbits and human beings, and provided the experimental basis for R-BMB as a lipid lowering drug. Aim: to investigate the effect of R-BMB on lowering blood lipid in animals and human body, and to speculate the mechanism and mechanism of R-BMB. Methods: (1) the hyperlipidemia model of Apo E-r-mice was established, and R-BMBs were administered intragastrically. (2) the hyperlipidemia model of rabbits was established by high cholesterol feeding. R-BMB was given to rabbits and blood lipids were measured at different time points. (3) in a randomized phase I clinical trial, the plasma cholesterol and related lipoproteins were measured, and the key pharmacokinetic parameters were combined. To analyze the decline of blood lipids in healthy subjects after oral administration of different doses of R-BMB. Results: (1) there was no significant change of blood lipid in Apo E-r-mice after R-BMB administration, and (2) after hyperlipidemia feeding, the level of serum lipids (TCU LDL-C) in rabbits was significantly increased, and the hyperlipidemia rabbit model was successfully established. After administration of R-BMB, plasma TC and LDL-C decreased significantly in hyperlipidemia model rabbits (P0.05), while TG and HDL-C levels did not change significantly (P0.05). (3) after taking different doses of R-BMB. The levels of LDL-C and TC decreased significantly in clinical subjects (P0.05), and HDL-C decreased in a short period of time, but returned to the level before administration. R-BMB was more effective than BMB in reducing blood lipids. Conclusion: R-BMB has no effect on lipid reduction in Apo-E-r-mice. However, R-BMB significantly decreased the levels of LDL-C and TC in rabbits. R-BMB can reduce plasma LDL-C and TC levels in human body. The effect of R-BMB on the decrease of LDL-C is the most obvious, and it has a dose-dependent effect. In this experiment, R-BMB has no significant effect on TG level. R-BMB has a better lipid lowering prospect than Rac-BMB.
【学位授予单位】：华南理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R589.2
【参考文献】
相关期刊论文 前1条
1 戴学栋;尹苗;荆文;杜会芹;叶红燕;商允菊;张晾;邹艳艳;曲志萍;潘杰;;apoE/LDLR双基因缺失幼龄小鼠主动脉中动脉粥样硬化相关基因的表达[J];生理学报;2008年01期
，本文编号：2147534
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