基于脂质代谢紊乱探讨丹红注射液对高脂血症大鼠的降脂作用及机制  

Lipid-lowering effect and mechanism of Danhong Injection on hyperlipidemia rats based on lipid metabolism disorder

作　　者：杜海霞 周惠芬[1] 何昱[1] 万海同[1] 杨洁红 DU Hai-xia;ZHOU Hui-fen;HE Yu;WAN Hai-tong;YANG Jie-hong(Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学,浙江杭州310053

出　　处：《中国中药杂志》2020年第13期3203-3210,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81874366,81873226);浙江省自然科学基金项目(LZ17H270001,LQ19H270001)。

摘　　要：制作大鼠高脂血症动物模型,探讨丹红注射液对高脂血症大鼠的降脂作用及作用机制。选用SD大鼠为研究对象,正常组饲以基础饲料喂养,其余组采用高脂饲料喂养法建立高脂血症大鼠模型,将造模成功的大鼠随机分为模型组,丹红注射液低、中、高剂量(1.0,2.0,4.0 mL·kg^-1)组,辛伐他汀(2.0 mg·kg^-1)组。丹红注射液组腹腔给药,辛伐他汀组灌胃给药,每天1次,连续给药4周。在给药后第1,2,3,4周周末,眼眶静脉采血,检测各组大鼠血脂总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)含量,并计算其动脉粥样硬化指数(AI)。并在给药4周后,处死动物,摘取心脏、肝、脾、肺、肾和脂肪组织,分别称重,计算各组大鼠器官指数;采用荧光定量PCR法检测肝脏中酯酰辅酶A氧化酶1(Acox1)、腺苷5′-单磷酸(AMP)激活的蛋白激酶α(AMPK-α)、胆盐输出泵(BSEP)、过氧化物酶体增殖物激活受体γ(PPAR-γ)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)mRNA的表达;ELISA法检测血清中胆固醇酯转运蛋白(CETP)、卵磷脂胆固醇酰基转移酶(LCAT)的含量。结果发现,与正常组相比,模型组大鼠血清TC,TG,LDL-C水平显著升高,HDL-C水平显著降低,表明成功构建高脂血症大鼠模型。与模型组相比,丹红注射液可以降低高脂血症大鼠体内血脂TC,TG,LDL-C含量,升高HDL-C含量;降低高脂血症大鼠体质量,下调肝脏质量及肝指数、脂肪质量及脂肪指数;对心脏、脾、肺和肾等主要脏器指数未产生明显影响;并可升高大鼠肝脏Acox1,AMPK-α,BSEP,PPAR-γ,CAT和SOD mRNA表达;使血清中CETP水平降低,LCAT水平升高;且丹红注射液各剂量组的调控作用表现出一定的剂量依赖性。结果表明,丹红注射液可调节高脂血症大鼠体内血脂含量,降低血脂水平,缓解体内脂肪堆积,其机制可能与抑制高脂饲料喂养引起的大鼠脂质代谢紊乱和氧化�The animal model of hyperlipidemia in rats was established to investigate the lipid-lowering effect and mechanism of Danhong Injection on hyperlipidemic rats.SD rats were selected as the research object.The rats in normal group were fed with basic diet,and the rats in other groups were fed with high-fat diet to establish hyperlipidemia model.The successfully modeled rats were randomly divided into model group,Danhong Injection low,medium,high dose(1.0,2.0,4.0 mL·kg^-1)groups,and simvastatin(2.0 mg·kg^-1)group.Danhong Injection groups received intraperitoneal administration,and simvastatin group received intragastrical administration,once a day for 4 weeks.At the first,second,third,and fourth weekends after administration,blood was collected from the orbital vein to detect the levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and then the atherosclerosis index(AI)was calculated.After 4 weeks of administration,the animals were sacrificed,and their heart,liver,spleen,lung,kidney and adipose tissue were extracted and weighed respectively to calculate the organ index of each group.The expressions of acyl-coaoxidase 1(Acox1),adenosine 5′-monophosphate(AMP)-activated protein kinase alpha(AMPK-α),bile salt export pump(BSEP),peroxisome proliferator-activated receptor gamma(PPAR-γ),catalase(CAT)and superoxide dismutase(SOD)mRNA in liver tissues were detected by fluorescence quantitative PCR;the content of cholesteryl ester transfer protein(CETP)and lecithin cholesterol acyltransferase(LCAT)in serum was detected by ELISA.The results showed that as compared with the normal group,the levels of serum TC,TG and LDL-C in the model group were significantly increased,and the level of HDL-C was significantly decreased,indicating that the hyperlipidemia rat model was successfully constructed.As compared with the model group,Danhong Injection could decrease the contents of TC,TG,LDL-C and increase the content of HDL-C in hyperlipidemia rat

关 键 词：丹红注射液 高脂血症 血脂水平 脂质代谢 

分 类 号：R285.5[医药卫生—中药学]