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1.400016 重庆,重庆医科大学:基础医学院组织学与胚胎学教研室
2.400016 重庆,中医药防治代谢性疾病重庆市重点实验室
3.400016 重庆,重庆医科大学:中医药学院
[王建伟,E-mail: wjwcq68@163.comWANG Jianwei, E-mail: wjwcq68@163.com
收稿:2021-10-26,
修回:2022-01-05,
纸质出版:2022-04-30
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刘宇哲, 詹权操, 曾颜, 等. 6-姜辣素改善果糖所致中年大鼠骨骼肌异位脂质沉积的研究[J]. 陆军军医大学学报, 2022,44(8):765-773.
Yuzhe LIU, Quancao ZHAN, Yan ZENG, et al. 6-gingerol ameliorates ectopic lipid accumulation in skeletal muscle of middle-aged rats induced by fructose[J]. Journal of Army Medical University, 2022, 44(8): 765-773.
刘宇哲, 詹权操, 曾颜, 等. 6-姜辣素改善果糖所致中年大鼠骨骼肌异位脂质沉积的研究[J]. 陆军军医大学学报, 2022,44(8):765-773. DOI: 10.16016/j.2097-0927.202110157.
Yuzhe LIU, Quancao ZHAN, Yan ZENG, et al. 6-gingerol ameliorates ectopic lipid accumulation in skeletal muscle of middle-aged rats induced by fructose[J]. Journal of Army Medical University, 2022, 44(8): 765-773. DOI: 10.16016/j.2097-0927.202110157.
目的
2
探究6-姜辣素改善果糖所致中年大鼠骨骼肌异位脂质沉积的作用及机制。
方法
2
动物实验:将24只15月龄雄性SD大鼠采用随机数字表法分为3组:对照组(CON,正常饮水),模型组(FRU,10%果糖水),6-姜辣素组(GIN,10%果糖水,0.2 mg/kg 6-姜辣素),每组8只,6-姜辣素通过灌胃给药,每日1次,持续49 d。采用酶法检测血浆葡萄糖(GLU)、甘油三酯(TG)及骨骼肌组织TG水平;油红O染色(ORO)检测骨骼肌组织脂质沉积;ELISA检测血浆胰岛素(Insulin);Western blot检测骨骼肌AMPK、p-AMPK、ACC、p-ACC、CPT1A、PPARα及PGC1α蛋白表达。细胞实验:将分化成熟的大鼠骨骼肌细胞分为3组:对照组(CON),模型组(FRU,25 mmol/L果糖),6-姜辣素组(GIN,25 mmol/L果糖,10 μmol/L 6-姜辣素),作用24 h。酶法检测细胞内TG水平;ORO检测骨骼肌细胞脂质沉积;Western blot检测骨骼肌细胞AMPK、p-AMPK、ACC、p-ACC及CPT1A蛋白表达。
结果
2
与对照组比较,模型组血浆GLU、TG及Insulin水平明显升高(
P
<
0.05),大鼠骨骼肌组织及骨骼肌细胞内TG含量明显升高(
P
<
0.05),ORO示大鼠骨骼肌组织及骨骼肌细胞内脂质沉积明显,Western blot示p-AMPK/AMPK及p-ACC/ACC降低,CPT1A、PPARα及PGC1α蛋白表达明显降低(
P
<
0.05);与模型组比较,姜辣素组血浆GLU、TG及Insulin水平明显降低(
P
<
0.05),大鼠骨骼肌组织及骨骼肌细胞内TG含量显著降低(
P
<
0.05),ORO示大鼠骨骼肌及骨骼肌细胞内脂质沉积减轻,Western blot示p-AMPK/AMPK及p-ACC/ACC明显升高,CPT1A、PPARα及PGC1α蛋白表达明显升高(
P
<
0.05)。
结论
2
6-姜辣素可改善果糖所致中年大鼠骨骼肌异位脂质沉积,可能与骨骼肌AMPK/ACC/CPT1A通路的激活有关。
Objective
2
To investigate the effect and mechanism of 6-gingerol on improving ectopic lipid accumulation in skeletal muscle of middle-aged rats induced by fructose.
Methods
2
A total of 24 male SD rats (15 months old) were randomly and equally divided into 3 groups: control group (CON
with normal drinking water)
model group (FRU
with 10% fructose water) and 6-gingerol group (GIN
with 10% fructose water+0.2 mg/kg 6-gingerol by gavage). Gavage was performed once a day for consecutive 49 days. Levels of plasma glucose (GLU)
triglyceride (TG) and skeletal muscle TG were measured by GOD-PAP method; lipid accumulation in skeletal muscle was detected by oil red O staining (ORO); content of plasma insulin was determined by ELISA; protein levels of AMP-activated protein kinase (AMPK)
p-AMPK
acetyl-coa carboxylase (ACC)
p-ACC
carnitine palmitoyltransferase 1A (CPT1A)
peroxisome proliferator activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in skeletal muscle were examined with Western blotting. L6 rat skeletal muscle cells were divided into 3 groups: control group (Con)
model group (FRU
treated with 25 mmol/L fructose for 24 h) and 6-gingerol group (GIN
treated with 25 mmol/L fructose+10 μmol/L 6-gingerol for 24 h). TG level and lipid accumulation in L6 cells were determined by GOD-PAP and ORO staining
respectively. The expression of AMPK
p-AMPK
ACC
p-ACC and CPT1A was examined by Western blotting.
Results
2
As compared with control group
the rat model group had higher levels of plasma GLU
TG and insulin (
P
<
0.05)
elevated TG content in both skeletal muscle tissues and cells (
P
<
0.05)
as well as notable lipid accumulation in skeletal muscle tissues and cells (
P
<
0.05). Western blotting showed that the p-AMPK/AMPK ratio
p-ACC/ACC ratio
and the protein levels of CPT1A
PPARα and PGC1α were all decreased in the model group (
P
<
0.05). However
6-gingerol significantly reduced the levels of plasma GLU
TG and insulin (
P
<
0.05)
alleviated the TG contents and lipid accumulation in skeletal muscles and cells (
P
<
0.05)
and greatly increased the p-AMPK/AMPK ratio
p-ACC/ACC ratio and the levels of CPT1A
PPARα and PGC1α in the GIN group (
P
<
0.05).
Conclusion
2
6-gingerol can improve the ectopic lipid accumulation in skeletal muscle of middle-aged rats induced by fructose
which may be related to the activation of AMPK/ACC/CPT1A pathway.
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