积雪草酸对高脂血症金黄地鼠的血脂调节及肝脏保护作用研究

摘要

目的：研究积雪草酸（asiatic acid，AA）对饮食性高脂血症金黄地鼠的血脂调节和肝脏保护作用，探讨其降脂机制。方法将48只叙利亚金黄地鼠随机分为6组，分别为正常对照组、高脂血症模型组、阳性对照药血脂康组（250 mg/kg）、AA低剂量组（8 mg/kg）、AA中剂量组（16 mg/kg）和AA高剂量组（32 mg/kg）。正常组给予普通饲料，其余各组均给予高脂饲料造模，自由进食和饮水。同时灌胃给药，正常组和模型组按体重给予溶媒（Tween 80去离子水＝119），其余各组给予相应受试药物。4周后测定血清总胆固醇（total cholestrol，TC）、甘油三酯（triglyceride，TG）、低密度脂蛋白（low-density lipoprotein）、高密度脂蛋白（high-density lipoprotein）、谷草转氨酶（aspartate transaminase ）和谷丙转氨酶（alanine aminotransferase ）水平，肝脏超氧化物歧化酶（superoxide dismutase）、谷胱甘肽过氧化物酶（glutathione peroxidase）水平以及观察肝脏结构变化。同时采用实时荧光定量PCR方法考察肝脏中卵磷脂胆固醇酰基转移酶（lecithin cholesterol fatty acyl transferase）和B类Ⅰ型清道夫受体（class B typeⅠscavenger receptor）mRNA的表达。结果与模型组相比，除AA高剂量组外，其余各给药组TC、TG、LDL-C、TC/HDL、AST、ALT水平均显著降低，SOD活性及GSH-Px水平均显著升高（P＜0.01）。HE染色结果显示AA给药后抑制了高脂血症金黄地鼠的肝脏脂肪性病变。荧光定量PCR结果显示AA各给药组金黄地鼠肝脏中LCAT和SR-BⅠmRNA表达水平增加。结论 AA可有效调节血脂，并通过降低AST、ALT水平和抗氧化作用减轻高脂血症金黄地鼠的肝脏损伤。AA的降血脂机制及保护肝脏作用，可能与其增强 LCAT和SR-BⅠmRNA的表达有关。%Objective To observe the protective effect of asiatic acid on hyperlipidemia golden hamsters induced by high fat diet and explore its mechanism.Methods Hyperlipidemic golden hamsters fed with high-fat diet were administered orally with asiatic acid (8,16,32 mg/kg)for 4 weeks.Levels of serum lipid content,liver histology,hepatic GSH-PX and SOD levels,serum ALT and AST activities were evaluated in golden hamsters,fluorescence quantitative polymerase chain reaction(RT-PCR)is using to examine the liver lecithin cholesterol fatty acyl transferase(LCAT) and class B typeⅠscavenger receptor(SR-BⅠ)mRNA expression. Results Compared with model group,the levels of TC,TG,LDL-C,TC/HDL,ALT and AST in low and mediate asiatic acid groups were all significantly decreased but the levels of SOD and GSH-PX were significantly increased(P<0.01).HE staining results showed that fat deposition in the liver were improved by administration of asiatic acid,and the expression of LCAT and SR-BⅠmRNA were increased.Conclusion Asiatic acid can effectively reduce blood lipid levels,and alleviate liver damage of the hyperlipidemia golden hamsters by lipid regulation and antioxidative ability augmentation.The increased levels of LCAT and SR-BⅠmRNA expression maybe involved in the mechanism of hypolipidaemic effect of asiatic acid.