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[多沙唑嗪及其对映体对喂饲致动脉粥样化饮食家兔血脂水平的影响]

[Effects of doxazosin and its enantiomers on serum lipid levels in rabbits fed by an atherogenic diet].

作者信息

Cao Xue-bin, Yang Mei, Wang Rong-ying, Ren Lei-ming

机构信息

Department of Phannrmacology, School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2010 May;26(2):241-6.

Abstract

OBJECTIVE

To observe the effects of (-)doxazosin(DOX), (+)DOX and (+/-)DOX on serum lipid levels and the mortality rates of the rabbits fed by an atherogenic diet.

METHODS

Male white New Zealand rabbits were fed by an atherogenic diet for 4 weeks. 8 rabbits whose serum TC <10 mmol/L were confirmed as normal diet group and were fed normally. 40 rabbits whose serum TC >10 mmol/L were randomly divided into 4 groups (n=10): atherogenic diet group, atherogenic diet with (-)DOX group, atherogenic diet with (+)DOX group and atherogenic diet with (+/-)DOX group, which were intraperitoneally injected with (-)DOX, (+)DOX and (+/-)DOX for 9 weeks respectively. Normal and atherogenic diet group were intraperitoneally injected with double distilled water. After 9 weeks administration of (+/-)doxazosin and its enantiomers, effects of the three agents on serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were observed.

RESULTS

The mortality rate of the rabbits fed by an atherogenic diet for 13 weeks was 40%, and it was much higher than that of the rabbits fed by a normal diet (10%). The mortality rates in the rabbits treated with (-)DOX and (+/-)DOX were lower than that in the rabbits fed by a normal diet (10%). Serum LDL-C level of the rabbits was increased markedly after 4 weeks of atherogenic diet, and it was further increased significantly (P < 0.05 and P < 0.01) during the continued 9 weeks of atherogenic diet. However, serum LDL-C levels were not further increased significantly (P > 0.05) during the continued 9 weeks of atherogenic diet in the rabbits treated with (-)DOX, (+)DOX and (+/-)DOX, respectively.

CONCLUSION

(-)DOX and (+/-)DOX increase the survival rate and improve LDL-C disorder mildly in the rabbits fed by an atherogenic diet. The improvements in LDL-C induced by (-)DOX and (+/-)DOX, however, might not be the reason for exploration about the increased survival rate in the rabbits fed by an atherogenic diet.

摘要

目的

观察左旋多沙唑嗪(DOX)、右旋多沙唑嗪(+)DOX和消旋多沙唑嗪(+/-)DOX对喂饲致动脉粥样硬化饮食家兔血脂水平及死亡率的影响。

方法

雄性新西兰白兔喂饲致动脉粥样硬化饮食4周。将血清总胆固醇(TC)<10 mmol/L的8只家兔确认为正常饮食组并正常喂养。将血清TC>10 mmol/L的40只家兔随机分为4组(n = 10):致动脉粥样硬化饮食组、致动脉粥样硬化饮食+左旋多沙唑嗪组、致动脉粥样硬化饮食+右旋多沙唑嗪组和致动脉粥样硬化饮食+消旋多沙唑嗪组,分别腹腔注射左旋多沙唑嗪、右旋多沙唑嗪和消旋多沙唑嗪9周。正常饮食组和致动脉粥样硬化饮食组腹腔注射双蒸水。消旋多沙唑嗪及其对映体给药9周后,观察三种药物对血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)水平的影响。

结果

喂饲致动脉粥样硬化饮食13周的家兔死亡率为40%,远高于正常饮食组家兔(10%)。左旋多沙唑嗪和消旋多沙唑嗪处理组家兔的死亡率低于正常饮食组家兔(10%)。致动脉粥样硬化饮食4周后家兔血清LDL-C水平显著升高,在继续致动脉粥样硬化饮食的9周内进一步显著升高(P<0.05和P<0.01)。然而,左旋多沙唑嗪、右旋多沙唑嗪和消旋多沙唑嗪处理的家兔在继续致动脉粥样硬化饮食的9周内,血清LDL-C水平均未进一步显著升高(P>0.05)。

结论

左旋多沙唑嗪和消旋多沙唑嗪可提高喂饲致动脉粥样硬化饮食家兔的存活率,并轻度改善LDL-C紊乱。然而,左旋多沙唑嗪和消旋多沙唑嗪诱导的LDL-C改善可能不是探索喂饲致动脉粥样硬化饮食家兔存活率增加的原因。

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