白藜芦醇通过诱导自噬减少肥胖小鼠骨骼肌组织GDF8表达的研究

Mechanism study of resveratrol decreasing expression of GDF8 via autophagy in skeletal muscle of obese mice

目的研究白藜芦醇(resveratrol,RES)通过诱导自噬减少肥胖小鼠骨骼肌组织中GDF8的表达。方法将8周龄C57BL/6雄性(♂)小鼠随机分为标准饮食组(SCD)、标准饮食+白藜芦醇组(SCD+RES)、高脂组(HFD)及高脂+白藜芦醇组(HFD+RES),白藜芦醇(400 mg·kg^-1·d^-1)胃饲,共持续20周。分析血脂指标和骨骼肌组织的形态学变化,免疫组化、RT-PCR和Western blot检测SIRT1、LC3、p62、GDF8的定位和表达。结果HFD组小鼠体质量、血脂指标TC、TG、LDL-C水平升高,HDL-C水平明显降低;骨骼肌纤维间出现脂肪沉积;SIRT1、LC3表达量明显减少,GDF8、p62的表达增加,且均定位于胞质;SIRT1、LC3的表达明显降低。与HFD小鼠相比,HFD+RES组小鼠体质量、血脂指标明显下降,HDL-C水平升高,骨骼肌中的脂质沉积明显减少,SIRT1、LC3的表达水平增高,GDF8、p62的表达水平明显降低。结论白藜芦醇有降低骨骼肌GDF8表达的效应,其机制可能与其激活SIRT1进而增加自噬、促进GDF8的降解有关。

Aim To investigate the mechanism of resveratrol decreasing GDF8 expression via activating autophagy in skeletal muscle of obese mice.Methods Male C57BL/6 mice were randomly divided into standard control diet(SCD),SCD treated with resveratrol(SCD+RES),high-fat diet(HFD)and high-fat diet group treated with resveratrol(HFD+RES).The SCD+RES and HFD+RES groups were intervened with resveratrol via gavage daily(400 mg·kg^-1·d^-1)for 20 weeks.The body mass,serum TG,TC,LDL-C and HDL-C levels were detected.The pathological changes in skeletal muscle were detected by HE staining.The mRNA,protein distribution and expression of SIRT1,LC3,p62 and GDF8 were assessed by immunohistochemistry,RT-PCR and Western blot respec-tively.Results The body mass,serum TG,TC and LDL-C levels increased,while HDL-C levels decreased in HFD group.Lipid deposition between skeletal muscle fibers was obvious in HFD group.The mRNA and protein expressions of GDF8 and p62 increased,while the mRNA and protein expressions of SIRT1 and LC3 decreased.All the response was attenuated by treatment with resveratrol.Conclusions High-fat diet induces lipid depostion and decreases autophagy in skeletal muscle.Resveratrol treatment significantly attenuates GDF8 expression in skeletal muscle tissues,which may be related with activated SIRT1and induced autophagy,thus resulted in the degradation of myostatin.