Effects of p-hydroxyacetophenone on bile secretion and blood lipid levels in rats
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摘要: 目的 研究对羟基苯乙酮（PHA）促胆汁分泌和降血脂作用以及初步作用机制。 方法 正常SD大鼠行胆管插管术，收集给药前30 min和给药后3 h分泌的胆汁，测定胆汁单位时间内的分泌量和胆汁成分；建立大鼠高血脂模型，观察PHA的降胆固醇作用；制备正常大鼠可溶性HMG-CoA还原酶，测定PHA对HMG-CoA还原酶活性的影响；对大鼠高胆固醇血症实验中得到的动物肝脏样本，进行Real-time PCR试验。 结果 PHA可以增加实验大鼠胆汁和胆汁酸的分泌量；同时能够显著降低高胆固醇血症大鼠的胆固醇水平，具有调血脂作用；初步的作用机制研究显示，PHA抑制HMG-CoA还原酶活性的作用较弱，但可以促进影响胆汁酸外排及胆固醇转化的AQP8、CYP7A1、OATP、NTCP等基因的转录。 结论 PHA作为茵陈中一种有效的单体化合物，可用于促进胆汁分泌、调节血脂代谢药物的研发。Abstract: Objective To study the effects and mechanism of p-hydroxyacetophenone (PHA) on bile secretion, cholesterol metabolism and blood lipids. Methods Cystic duct cannula was cannulated and bile were collected in SD rats.PHA was administrated in the high cholesterol rats. The activity of HMG-CoA reductase was determined by spectrophotometry in reaction system. Samples of liver were obtained in experiment hypercholesterolemia rats and Real-time PCR test was conducted for AQP8, CYP7A1, OATP and NTCP. Results Secretion of bile were increased, cholesterol in bile were reduced and secretion of total bile acid were increased in rats by PHA. The level of serum cholesterol in hyperglycemia rat model was reduced significantly and inhibitory ability had been limited in the activity of HMG-CoA reeducates by PHA, but the gene transcription including AQP8, CYP7A1, OATP, and NTCP were promoted, which are related to function of excretion of biliary acid and transformation of cholesterol. Conclusion These results suggest that PHA, as a lead compound, might be of significance for further development for a bile secretory and lipid lowering agent.
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Key words:
- p-hydroxyacetophenone(PHA) /
- artemisiae capillaries /
- choleretic /
- cholesterol
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