西罗莫司抑制脂肪酸摄取改善小鼠肝脏脂质积聚

发布时间：2018-04-24 05:13

本文选题：西罗莫司 + 脂肪酸　；参考：《重庆医科大学学报》2017年07期

【摘要】：目的:研究西罗莫司对小鼠肝脏脂质积聚的影响及机制初探。方法:6~8周龄雄性C57BL/6J小鼠,随机分为3组:A组为普通饮食组(n=12),B组为高脂饮食组(n=9),C组为高脂饮食加隔天注射西罗莫司组(n=7),喂养14周。全自动生化分析仪检测血清生化指标。酶联免疫吸附法和酶偶联比色法分别检测肝脏游离脂肪酸(free fatty acid,FFA)和甘油三酯(triglyceride,TG)的含量。Western blot检测脂肪酸转运酶(fatty acid translocase,FAT/CD36)蛋白的表达水平。荧光显微镜观察原代肝细胞对荧光标记FFA的动态摄取。结果:与A组相比,B组小鼠体质量(q=6.68,P=0.000),血清TG(q=4.88,P=0.045),高密度脂蛋白(high-density lipoprotein,HDL)(q=6.311,P=0.002),谷草转氨酶(aspirate aminotransferase,AST)(q=8.84,P=0.001)水平明显增高,肝脏组织TG(q=14.4,P=0.000),FFA(q=18.0,P=0.000)也明显增高。C组小鼠较B组体质量(q=7.99,P=0.000),血清TG(q=4.636,P=0.050),AST(q=5.16,P=0.016)及肝脏TG(q=8.91,P=0.000)和FFA(q=14.1,P=0.000)都显著降低。Western blot结果显示C组小鼠肝脏CD36的蛋白表达水平较B组明显降低。FFA动态摄取实验通过定量荧光强度显示西罗莫司能明显抑制肝细胞对FFA的摄取速度(各时间点P均0.05)。结论:西罗莫司能抑制肝细胞对外源性FFA的摄取,减轻肝脏脂质积聚,其作用机制可能与CD36相关。
[Abstract]:Objective: to study the effect and mechanism of sirolimus on lipids accumulation in mice. Methods male C57BL/6J mice at the age of 6 to 8 weeks were randomly divided into 3 groups: group A, normal diet group, group B, group B, high fat diet group, group C, high fat diet plus sirolimus group for the next day, fed for 14 weeks. The serum biochemical indexes were detected by automatic biochemical analyzer. The content of free fatty acid (FFA) and triglyceride triglyceride (TGG) in liver were detected by enzyme-linked immunosorbent assay (Elisa) and enzyme-coupled colorimetry (Elisa) respectively. Western blot was used to detect the expression of fatty acid translocase / FATP / CD36 protein. Fluorescence microscopy was used to observe the dynamic uptake of fluorescent labeled FFA in primary hepatocytes. Results: compared with group A, the body weight of mice in group B was significantly higher than that in group A (P 0.000), the levels of serum TGQ, 4.88 and 0.045, high density lipoprotein, high density lipoprotein, high density lipoprotein, high density lipoprotein, high density lipoprotein, and aspartate aminotransferase ASA, 8.84, P0. 001 were significantly higher in group B than in group A (P < 0.05), and the levels of high density lipoprotein in group B were significantly higher than those in group A (P < 0.05). Liver tissue (TGQN 14.4P0.000) and FFAq14.1P0.000) also significantly increased compared with group B. the expression of CD36 protein in group C was significantly lower than that in group B, and the level of serum TGGQ (4.636), ASTq5.16P0.016) and liver TGQ (8.91) and FFAq14.1P0.000) were significantly decreased. The results of Western blot showed that the protein expression level of liver CD36 in group C was significantly lower than that in group B (P 0.016). The results of Western blot showed that the protein expression level of liver CD36 in group C was significantly lower than that in group B (P < 0.01). The results of Western blot showed that the protein expression level of liver CD36 in group C was significantly lower than that in group B (P < 0.01). The results of Western blot showed that the protein expression of liver CD36 in group C was significantly lower than that in group B. The over-quantitative fluorescence intensity showed that sirolimus could significantly inhibit the uptake of FFA by hepatocytes (P < 0.05). Conclusion: sirolimus can inhibit the uptake of exogenous FFA and alleviate the accumulation of lipids in liver cells. The mechanism of sirolimus may be related to CD36.
【作者单位】：重庆医科大学脂糖代谢性疾病重庆市重点实验室;
【基金】：国家自然科学基金资助项目(编号:81400786) 重庆市科委基础与前沿研究计划资助项目(编号:cstc2015jcyj A10001)
【分类号】：R575.5

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