中文摘要：

目的观察肌肉注射化学表面活化剂Triton WR-1399诱导小鼠急性高脂血症模型,考察时效和量效关系,并从基因水平探讨Triton WR-1399诱发高脂血症动物模型的机制。方法用肌肉注射的方式分别给予小鼠0.4 g·kg（-1）,0.8 g·kg（-1）和1.5 g·kg（-1）的Triton WR-1399,取血时间点为24、32、48、56、72、80和96 h,观察这7个时间点小鼠甘油三酯（TG）、胆固醇（TC）、低密度脂蛋白（LDL-C）和高密度脂蛋白（HDL-C）的变化;采用荧光定量PCR（RT-q PCR）法检测脂蛋白脂肪酶（LPL）,胆固醇脂酰转移酶（LCAT）,胆固醇7-羟化酶（CYP7A1）,载脂蛋白AI（Apo AI）,载脂蛋白（Apo B）,低密度脂蛋白受体（LDLR）,B类Ⅰ型清道夫受体（SRB1）和羟甲基戊二酰辅酶A还原酶（HMGCR）的脂质代谢相关通路基因mRNA相对表达量变化。基于模型复制方法考察,研究贝特类和他汀类代表药物的调脂作用,验证模型的稳定性。结果 Triton WR-1399（0.8 g·kg（-1）,1.5 g·kg（-1））剂量组的TC、TG和LDL-C水平明显升高,LPL、LDLR、Apo B和SRB1的基因相对表达明显降低,HMGCR的基因相对表达明显升高;非诺贝特对该急性模型有明显降脂作用。结论采用肌肉注射0.8 g·kg（-1）Triton WR-1399所诱导的急性高脂血症小鼠模型稳定,可用于调脂药物筛选,其诱导模型的机制可能与抑制VLDL-C代谢通路和阻断胆固醇逆向转运过程有关。基于该模型的发病机制,非诺贝特比瑞舒伐他汀表现出更为明显的降脂作用。

英文摘要：

Aim Toinvestigatethetimeanddosage-dependent relationship in Triton WR-1399 -induced acute hyperlipidemia mice models and explore the underlying mechanism in gene rela-tiveexpression.Methods Miceweregivendifferentdosagesof Triton WR-1399（0. 4 g·kg-1 ,0. 8 g·kg-1 ,1. 5 g·kg-1 ） through im and blood was collected at different time（24 h,32 h, 48 h,56 h,72 h,80 h and 96 h）to observe the changes of TG, TC,LDL-C and HDL-C in HLP mice models.RT-qPCR was uti-lized to detect gene relative expression of LPL,LDLR,ApoA1 , ApoB,LCAT,SRB1,CYP7A1 and HMGCR.To verify stability of this model,fenofibrate and rosuvastatin were adapted to inves-tigate the mechanism of lipid regulation based on the exploration ofacuteHLPmicemodels.Results TritonWR-1399（0.8g· kg-1 ,1. 5 g·kg-1 ）could significantly reduce the level of TC,TG,LDL-C and enhance the content of HDL-C.In addition,it obviously inhibited the gene relative expression of LPL,LDLR, ApoB andSRB1 , while HMGCR was significantly enhanced. Fenofibrate showed noble hypolipidemic efficacy in this model. Conclusions Theeffectivetimerangeforscreeninglow-choles-terol is 24 h~32 h after intramuscular injection of Triton WR-1399（0. 8 g·kg-1 ）and the underlying mechanism is likely as-sociated with inhibition of metabolic pathway of VLDL-C and block of the reverse cholesterol transport.Based on the mecha-nism of acute HLP mice models,fenofibrate performs stronger hy-polipidemic efficacy than rosuvastatin.