线粒体来源多肽MOTS-c对去卵巢小鼠肝脂代谢的改善作用

Improving function of mitochondria-derived peptide MOTS-c on the lipid metabolism of liver in ovariectomized mice

目的研究线粒体来源多肽MOTS-c对去卵巢(OVX)小鼠肝脂代谢的改善作用及其可能的作用机制。方法按照体重将小鼠随机分为3组:假手术组、模型组和实验组。实验组每日腹腔注射MOTS-c 10 mg·kg^(-1),连续8周。8周后检测血清游离脂肪酸和三酰甘油;用实时定量荧光聚合酶链反应检测肝组织微小RNA-181c-5p (mmu-miR-181c-5p)基因表达(2~(-△CT)值),蛋白质印迹法检测肝组织中过氧化物酶体增殖物活化受体α(PPARα)蛋白的相对表达量,双荧光素酶报告基因实验验证PPARα是mmu-miR-181c-5p靶基因。结果假手术组、模型组、实验组的游离脂肪酸分别为(0.06±0.01),(0.15±0.04)和(0.12±0.03)mmol·L^(-1);这3组的三酰甘油分别为(0.17±0.05),(0.34±0.05)和(0.30±0.08)mmol·L^(-1);这3组的mmu-miR-181c-5p相对表达量分别为(1.70±0.10)×10^(-2),(2.10±0.40)×10^(-2)和(1.70±0.20)×10^(-2);这3组的PPARα蛋白相对表达量分别为0.27±0.04,0.06±0.02和0.25±0.04。模型组的上述指标与假手术组比较,差异均有统计学意义(均P<0.05);实验组的上述指标与模型组比较,差异均有统计学意义(均P<0.05);PPARα是mmu-miR-181c-5p靶基因。结论 MOTS-c通过miR-181c-5p/PPARα可以改善去卵巢小鼠肝脂代谢。

Objective To study the effect of mitochondria-derived peptide(MOTS-c)on the improvement of lipid metabolism in ovariectomy(OVX)mice and the possible mechanism.Methods The mice were randomly divided into three groups according to weight:sham group,model group,experimental group.The mice of experimental group were injected intraperitoneally daily by MOTS-c for 10 mg·kg^(-1),for 8 weeks.The free fatty acids and triglycerides(TC)of serum were detected.Expression of miR-181c-5p gene in liver tissue was detected by real time fluorescence quantitative-PCR(2-△CT value).Western blot was used to measure the relative expression of peroxisome proliferator-activated receptorsα(PPARα)in liver.The double luciferase was used to confirm that PPARαwas the target gene of mmu-miR-181c-5p.Results The free fatty acids in sham group,model group,experimental group were(0.06±0.01),(0.15±0.04)and(0.12±0.03)mmol·L^(-1),respectively;the TC in the three groups were(0.17±0.05),(0.34±0.05)and(0.30±0.08)mmol·L^(-1),respectively;the expression of mmu-miR-181 c-5 p in the three groups were(1.70±0.10)×10^(-2),(2.10±0.40)×10^(-2) and(1.70±0.20)×10^(-2),respectively;and the relative expression of PPARαin the three groups were 0.27±0.04,0.06±0.02 and 0.25±0.04,respectively.compared between model group and sham group,the differences of the factors were significant(all P<0.05);compared between experimental group and model group,the differences of the factors were significant(all P<0.05).The PPARαwas the target gene of mmu-miR-181 c-5 p.Conclusion MOTS-c can improve lipid metabolism in OVX mice by mmu-miR-181 c-5 p/PPARαpathway.