性别差异对磷脂转运蛋白基因敲除小鼠胆固醇逆转运效率的影响

发布时间：2018-02-15 11:54

本文关键词： 磷脂转运蛋白胆固醇逆转运 H-胆固醇性别差异　出处：《中国现代医学杂志》2017年25期 　论文类型：期刊论文

【摘要】：目的观察磷脂转运蛋白基因敲除(PLTP~(-/-))后雌雄小鼠血浆脂质水平的差异,比较PLTP~(-/-)对雌雄小鼠胆固醇逆转运(RCT)效率的影响。方法选择8周龄同窝出PLTP~(-/-)小鼠雌雄各8只,喂饲高脂饲料4周后,酶法检测小鼠血浆中总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-Ch)和非高密度脂蛋白胆固醇(non-HDL-Ch)水平,Western blot检测血浆载脂蛋白A1(apo A1)表达,小鼠腹腔注射含~3H-胆固醇的巨噬细胞,48 h后,取小鼠血浆、肝脏、胆汁、小肠和粪便,利用液闪计数仪检测小鼠各组织中的放射活度,逆转录聚合酶链反应(RT-PCR)检测肝组织清道夫受体BI(SR-B1)、低密度脂蛋白受体(LDL-R)、三磷酸腺苷结合转运蛋白G5/G8(ABCG5/G8)、肝X受体α(LXRα)、胆固醇7α羟化酶(CYP7A1)、小肠ABCG5/G8和肝x受体α(LXRα)的基因表达。结果相比于雄性PLTP~(-/-)小鼠,雌性PLTP~(-/-)小鼠血浆中TC、TG、HDL-Ch和non-HDL-Ch的表达无明显改变,但apo A1水平,差异有统计学意义(P0.05),雌性PLTP~(-/-)小鼠升高;体内RCT实验显示:与雄性PLTP~(-/-)小鼠相比,雌性PLTP~(-/-)小鼠血浆和小肠中放射活度无变化,肝脏、胆汁和粪便中放射活度,差异有统计学意义(P0.05),雌性PLTP~(-/-)小鼠升高;RT-PCR显示:与雄性PLTP~(-/-)小鼠相比,雌性PLTP~(-/-)小鼠肝脏中RCT相关因子LXRα、ABCG5/G8及CYP7A1表达,差异有统计学意义(P0.05),雌性PLTP~(-/-)小鼠升高,而SR-B1、LDL-R表达无明显变化;小肠壁LXRα、ABCG5/G8表达未见明显变化。结论磷脂转运蛋白基因敲除后,雌性PLTP~(-/-)小鼠的胆固醇逆转运效率较高于雄性PLTP~(-/-)小鼠,肝脏中RCT相关蛋白基因表达增加。
[Abstract]:Objective To observe the effect of phospholipid transfer protein gene knockout (PLTP~ (- / -)) the difference between male and female mice serum lipid levels, PLTP~ (- / -) mice of reverse cholesterol transport (RCT) effect. Methods 8 week old littermates PLTP~ (- / -) mice and 8 rats each, fed with high fat diet after 4 weeks, the total cholesterol in plasma were detected by enzyme (TC), three glycerol (TG), high density lipoprotein cholesterol (HDL-Ch) and non high density lipoprotein cholesterol (non-HDL-Ch) level, Western blot detection of plasma apolipoprotein A1 (apo A1) expression in macrophages by intraperitoneal injection of ~3H- containing cholesterol mice, after 48 h, the mice plasma, liver, bile, small intestine and feces, radioactivity by liquid scintillation counting was detected in various tissues of mice, reverse transcriptase polymerase chain reaction (RT-PCR) detection of scavenger receptor BI in liver tissue (SR-B1), low density lipoprotein receptor (LDL-R), ATP binding. Transport protein G5/G8 (ABCG5/G8), liver X receptor alpha (LXR alpha), cholesterol 7 alpha hydroxylase (CYP7A1), ABCG5/G8 in the small intestine and liver X receptor alpha (LXR alpha) gene expression. Results compared to the male PLTP~ (- / -) mice, female PLTP~ (- / -) mice plasma TC, TG, no significant change the expression of HDL-Ch and non-HDL-Ch, but the apo level of A1, the difference was statistically significant (P0.05), female PLTP~ (- / -) mice increased; RCT showed that in vivo experiment: with male PLTP~ (- / -) mice compared to female PLTP~ (- / -) without radioactivity changes in plasma and small intestine in mice liver, bile and feces radioactivity, the difference was statistically significant (P0.05), female PLTP~ (- / -) mice increased; RT-PCR showed that: male PLTP~ (- / -) mice compared to female PLTP~ (- / -) mouse liver RCT related factor LXR alpha, the expression of ABCG5/G8 and CYP7A1, the difference was statistically significant (P0.05), female PLTP~ (- / -) mice increased. The expression of LDL-R and SR-B1, no obvious Change; small intestine LXR alpha, there was no change in the expression of ABCG5/G8. Conclusion the phospholipid transfer protein gene knockout, female PLTP~ (- / -) mice reverse cholesterol transport efficiency is higher than that of male PLTP~ (- / -) mice, liver RCT related protein gene expression increased.

【作者单位】：泰山医学院山东省高校动脉粥样硬化重点实验室;
【基金】：山东省自然科学基金(No:ZR2013HL063) 山东省泰山学者岗项目(No:ts20151105)
【分类号】：R54

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