高脂高胆固醇饮食对3基因突变小鼠动脉粥样硬化性病变的影响

Effect of high fat/cholesterol diet on lipid metabolism and intimal lesion of aorta in treble genes mutant mice

目的:探讨高脂高胆固醇饮食性因素对3个脂代谢相关基因突变小鼠血脂代谢及动脉内膜损伤的影响。方法:分析高脂高胆固醇饮食喂养的3基因突变(ApoE-/-/LDLR-/-/Leprdb/db)小鼠血脂、血糖水平和主动脉内膜病变的特点。结果:高脂高胆固醇饮食喂养的3基因突变小鼠血浆总胆固醇(TC)、甘油三酯(TG)和血糖水平均显著高于普通饮食组。该饮食喂养2周和5周龄小鼠血浆TC、TG的浓度分别达(106.75±3.40)mmol/L和(9.12±1.35)mmol/L,高出普通饮食组4.33和2.36倍。主动脉内膜出现灶状内皮肿胀、脱落、单核/淋巴细胞黏附以及泡沫细胞形成。随喂养周数的增加出现内弹力板排列不整、部分断裂、内皮和平滑肌细胞内脂质沉积,并发生内膜增生型病变增多、范围扩大。血脂紊乱的加重与动脉内膜的损伤呈正相关。高脂高胆固醇饮食组小鼠的血脂紊乱和动脉内膜损伤均较普通饮食组严重,并伴有明显的肝细胞脂肪病变。结论:高脂高胆固醇饮食促进了3基因突变小鼠血脂代谢紊乱及主动脉内膜损伤的发生,提前并加重了动脉粥样硬化性病变的发生发展。

AIM ： To clarify the effects of high fat/cholesterol diet on lipid metabolism and atherogenesis in treble genes mutant mice. METHODS： APOE ^-/-/LDLR ^-/-/Lepr^db/db mice were generated by cross apolipoprotein E, lower density lipoprotein receptor gene knockout mice with leptin receptor gene spontaneous point mutants. The mice were fed with high fat/cholesterol diet from 22 - day - old. The total plasma cholesterol （TC）, triglyceride （TG） and glucose levels were measured and pathological changes of aorta intima and liver were analyzed. RESULTS： A significant elevated TC, TG and glucose levels in plasma with progress of time in young treble gene mutant mice were observed, which were higher than that in ApoE ^-/-/LDLR^ -/- and Lepr^db/db mutants. At time of only 2 weeks after fed with high fat/cholesterol diet, TC and TG levels reached （ 106.75 ±3.40） mmol/L, （9. 12 ± 1.35） mmol/L, respectively in treble gene mutant mice, 4. 33 - and 2. 36 - fold higher than those in treble genes mutants fed with normal chow diet. The levels were continuously increased until final experimental point. Intima of the aorta appeared with various injuries such as edema, desquamation of the endothelial cells, foam cell formation, rupture of IEL in local regions of root and arch areas of aorta at 2 weeks after fed with high fat/cholesterol diet. Microscopic pathological complex of significant local intima incrassation and fatty change of the liver were observed in the mutants that fed with high fat/cholesterol diet for 8 weeks. Injuries of aorta were severe than normal dietetic control group. CONCLUSION： High fat/cholesterol diet as a key dietary factor is significant aggravated lipid metabolism abnormity, promotes early damage of aorta and process of atherogenesis in the treble genes mutants.