机构地区:[1]河南中医药大学第一附属医院中药临床评价技术河南省工程实验室,郑州450000 [2]北京中医药大学中药学院,北京100102 [3]浙江中医药大学学生处,杭州310053 [4]河南中医药大学药学院,郑州450008 [5]香港科技大学生命科学部,香港999077
出 处:《中国新药杂志》2020年第14期1636-1641,共6页Chinese Journal of New Drugs
基 金:国家自然科学基金资助项目(81803702,31071989)。
摘 要:目的:探讨高甘油三酯血症模型建立的新方法及其可能机制,并观察以橄榄油(olive oil,OO)和羧甲基纤维素钠(carboxymethyl cellulose sodium,CMC)溶液配制五味子素B(schisandrin B,Sch B)对其诱发小鼠高甘油三酯血症(hypertriglyceridemia,hTG)模型的影响,以便优化本模型的制作过程。方法:ICR小鼠,雄性,分为、6组,每组10只动物:OO组、OO/Sch B组、OO/非诺贝特(fenofibrate,FF)组、CMC组、CMC/Sch B组CMC/FF组。Sch B和FF的剂量分别为1和0.15 g·kg^-1,一次灌胃给药后48h用生化法检测血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high-density lipoprotein,HDL)低密度脂蛋白胆固醇(low-density lipoprotein,LDL)、葡萄糖(glucose,GLU)水平和谷丙转氨酶(alanine aminotransferase,ALT)活性,以及肝TG和TC含量;血清载脂蛋白B48(apolipoprotein B48,ApoB48)和极低密度脂蛋白胆固醇(very low-density lipoprotein,VLDL)用酶联免疫法检测。结果:OO/Sch B和CMC/Sch B均可升高小鼠血清和肝,TG水平、降低肝GLU含量,但与CMC/Sch B组比较OO/Sch B组小鼠血清TG升高是前者的2.68倍肝TG升高是前者的4.02倍(P<0.01);OO组血清TG,TC和GLU与CMC组无明显差异,但OO组肝TG,TC和GLU水平高于CMC组(P<0.01);OO/Sch B组和CMC/Sch B组小鼠血清LDL水平均显著升高(P<0.01),但前者大于后者38.04%(P<0.01)。OO/Sch B和CMC/Sch B均可使小鼠肝指数增加(P<0.01),但前者比后者增加明显(P<0.05);OO/Sch B组小鼠血清ALT活性高于对照组81.14。%(P<0.01)。OO/Sch B和CMC/Sch B均抑制小鼠的体重增加,抑制率分别为47.78%和31.,90%结论:Sch B可成功诱导hTG小鼠模型,且用橄榄油配制Sch B诱导hTG模型优于用CMC溶液配制为hTG的研究提供了一种新的造模途径。Objective:To explore a new method of establishing hypertriglyceridemia(hTG)mouse model by schisandrin B(Sch B)and its possible mechanism and observe the effects of preparing Sch B with olive oil(OO)and carboxymethyl cellulose sodium(CMC)solution on the model,in order to optimize the productionprocess of this model.Methods:Male ICR mice with body weight of 23~27 g were randomly divided into sixgroups with ten animals in each:OO control group,OO/Sch B group,OO/FF group,CMC control group,CMC/Sch B group,and CMC/FF group.Single dose of Sch B(1 g·kg^-1)and FF(0.15 g·kg^-1)suspended in OO orCMC was int-ragastrically administered.Mice in the control groups received vehicle(i.e.,OO or 0.5%CMC solution)at 5 mL·kg^-1.Serum and hepatic triglyceride(TG),total cholesterol(TC)and glucose(GLU),as well as serumalanine aminotransferase(ALT)activity were determined 48 h later by biochemical method.Serum ApolipoproteinB48(Apo-B48),high-density lipoprotein(HDL),low-density lipoprotein(LDL),and very low-density lipoprotein(VLDL)levels were determined using enzyme-linked immunosorbent assay(ELISA).Results:Both OO/Sch Band CMC/Sch B could increase the level of TG in serum and liver and decrease the content of GLU in liver(P<0.01).However,the level of serum TG in OO/Sch B group was 2.68 times higher than that in CMC/Sch Bgroup,and the liver TG level in OO/Sch B group was 4.02 times higher than that in CMC/Sch B group(P<0.01).There was no significant difference in serum TG,TC and GLU levels between vehicle OO and CMC,however,the hepPatic TG,TC and GLU levels in the mice receiving OO were elevated compared with the micereceiving CMC(<0.01).OO/Sch B and CMC/Sch B treatment markedly increased serum LDL level,with anextra increase of 38.04%for the former(P<0.01).Both OO/Sch B and CMC/Sch B could increase the liverindex of mice(P<0.01),but the former had more significant effect than the latter(P<0.05).The activity ofserum ALT in OO/Sch B group was 81.14%higher than that in the control group(P<0.01).Both OO/Sch BaCnodn CclMusCio/Snch B inhi
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