摘要
目的 比较普伐他汀与依那普利和维拉帕米对SDR和SHR肝脏HMG CoA还原酶的抑制作用。方法 超速离心法制备肝微粒体 ,放射性同位素方法测定肝脏HMG CoA还原酶的活性。结果 普伐他汀明显抑制肝HMG CoA还原酶的活性 ,其IC50 为 0 2 8g·L-1。普伐他汀对SHR的肝HMG CoA还原酶的抑制率为 6 3 40 %± 4 14% ;对SDR的肝HMG CoA还原酶的抑制率为 5 1 40 %± 3 98% ,两者差异有显著性 (P <0 0 1)。依那普利和维拉帕米不抑制SDR和SHR肝HMG CoA还原酶的活性 ,其对SDR和SHR的肝HMG CoA还原酶的抑制率分别为 - 0 33%± 13 35 % ,5 90 %± 2 1 12 %和 2 6 0 %± 17 38% ,4 0 0 %± 19 6 9% ,与普伐他汀相比差异有显著性 (P <0 0 1)。结论 普伐他汀对SHR肝HMG CoA还原酶的抑制强于SDR ,提示普伐他汀能阻止SHR的胆固醇合成 ,降低其血清胆固醇 ,有利于高血压治疗。而依那普利和维拉帕米不抑制肝HMG CoA还原酶 ,提示其降脂作用不是通过对肝HMG
AIM To compare the inhibition of pravastatin on HMG CoA reductase with enalapril and verapamil in SDR and SHR liver. METHODS The liver microsomes were prepared by ultracentrifugation, the HMG CoA reductase activity was determined by radioactivity in vitro. RESULTS Pravastatin inhibited HMG CoA reductase, and its IC 50 value was 0 28 g·L -1 . The inhibitory rate of pravastatin on HMG CoA reductase in SDR and SHR liver were 51 40%±3 98% and 63 40%±4 14%, respectively (P<001). Enalapril and verapamil did not inhibit HMG CoA reductase. The inhibitory rate of enalapril and verapamil on HMG CoA reductase in SDR and SHR liver were -0 33%±13 35%, 5 90%±21 12% and 2 60%±17 38%,4 00%±19 69%, respectively. Enalapril and verapamil were significantly different from pravastatin p<0 01). CONCLUSION The inhibitory effects of pravastatin on HMG CoA reductase in SHR were more potent than that in SDR, while enalapril and verapamil did not inhibit activity of HMG CoA reductase. These results suggest that pravastatin greatly prevents the synthesis of cholesterol, decreases serum cholesterol in SHR, and it is in favor of the therapy of hypertension. The inhibitory mechanism of enalapril and verapamil on serum lipoprotein is irrelevant of HMG CoA reductase in SDR and SHR liver.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2001年第4期386-388,共3页
Chinese Pharmacological Bulletin
基金
中国科学院"九五"重大科研项目资助课题NoKZ95 1 B1 10 9 0 1 0 2
