四氢普伐他汀钠对高血脂模型新西兰兔脂质代谢的影响

Effect of tetrahydropravastatin sodium on lipid metabolism in hyperlipidemic New Zealand rabbits

目的通过高脂饮食兔高血脂模型考察四氢普伐他汀钠(H4PV-Na)的降血脂和调节脂质代谢的作用。方法新西兰白兔,雄性,100只,适应性饲养2周后,随机分为空白对照组、高脂模型组、阳性对照组P(普伐他汀钠组2.5mg·kg^(-1))、阳性对照组A(阿托伐他汀钙组2.5mg·kg^(-1))和给药组(低剂量1.25mg·kg^(-1)、中剂量2.5mg·kg^(-1)、高剂量5mg·kg^(-1))。高脂饲料喂饲2周形成高脂模型后,阳性药物和供试药物强制经口灌胃给药,10mL·kg^(-1),每天上午给药1次,每周给药6d,连续10周。最后1次给药后24h,禁食过夜,取血和肝脏组织,进行血脂和肝脂相关指标检测:血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、全血超氧化物歧化酶(SOD)活力和血清丙二醛(MDA)含量。横纹肌溶解毒性检测指标:测定血清磷酸肌酸激酶(CK)含量。取心脏、肝脏、脾脏、肺脏、肾脏、肾上腺等器官经HE染色检测脂肪组织的病理学变化。结果新西兰兔用高脂饲料喂养10周后,TC,TG和LDL-C水平升高,HDL-C水平降低,给予H4PV-Na后,TC、TG和LDL-C水平降低,HDL-C水平升高。结论 H4PV-Na具有明确的降血脂和胆固醇作用,在肝脏组织中降低胆固醇能力高于在血液中,无横纹肌溶解毒性,但在同等剂量下,H4PV-Na降脂效果稍弱于普伐他汀钠和阿托伐他汀钙。

Objective To explore the effect of tetrahydropravastatin sodium（H4PV-Na）on blood lipid and lipid metabolism in experimental hyperlipidemic New Zealand rabbits.Methods 100 New Zealand white rabbits（male）were randomly divided into normal control group,fat control group,positive control group P（pravastatin sodium,2.5mg·kg^-1）,positive control group A（atorvastatin calcium,2.5mg·kg^-1）and the treatment groups with low,medium and high dose（1.25,2.5and 5.0mg·kg^-1）after adaptive feeding for 2weeks.TC,TG,HDL-C,LDL-C,MDA,SOD and CK levels in serum and liver were determined after giving high fat diet and corresponding reagents orally for 10 weeks.The histopathological changes of the adipose tissues were detected with HE staining.Results After high fat diet for 10 weeks,TC,TG and LDL-C levels went up,while HDL-C levels went down.H4PV-Na could significantly lower the levels of TC,TG,LDL-C,and MDA in serum as well as in liver,and increase HDL-C levels and SOD activity after oral administration of H4PV-Na for 10 weeks.Conclusion H4PV-Na had a specific role in lowering serum lipid and cholesterol with the higher capacity in liver.The results also suggested that H4PV-Na could increase HDL-C levels and the SOD activity in hyperlipidemic rabbits without rhabdomyolysis toxicity,but the potential to lower the blood lipid is weaker than pravastatin sodium and atorvastatin calcium at the same dose.