期刊
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
卷 2018, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2018/2370617
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资金
- Beijing NOVA Program [Z171100001117027]
- Natural Science Foundation of Beijing [7162170]
- Key Projects in the National Science and Technology Pillar Program during the 12th Five-Year Plan Period [2011BAI11B05]
- Beijing Lab for Cardiovascular Precision Medicine [PXM2017_014226_000037]
Diabetes was induced in high-fat diet-fed ApoE(-/-) mice via administration of low-dose streptozotocin (STZ) for five days. Mice were then treated with GBE (200 or 400 mg/kg) by gastric gavage daily for 12 weeks. Mice in the untreated diabetic group received saline instead, and nondiabetic C57BL/6J mice served as controls. Collagen I and III mRNA expression was measured by real-time PCR. TNF-alpha, IL-1 beta mRNA levels, and NF-kappa B expression were determined to analyze intramyocardial inflammation. Hallmarks of endoplasmic reticulum stress- (ERS-) related apoptosis pathways, including phosphorylated c-Jun N-terminal kinase (p-JNK), C/EBP homologous protein (CHOP), caspase-12, and cleaved caspase-3, were analyzed by Western blotting. Diabetic ApoE(-/-) myocardial injury was associated with increased cardiomyocyte apoptosis (increased expression of p-JNK, CHOP, caspase-12, and cleaved caspase-3), interstitial fibrosis (increased mRNA levels of collagen I and III), and inflammation (increased mRNA levels of TNF-alpha and IL-1 beta, and NF-kappa B expression). GBE at 200 and 400 mg/kg/day significantly attenuated cardiomyocyte apoptosis, collagen deposition, and inflammation in diabetic mice via inhibition of the p-JNK, CHOP, and caspase-12 pathways. Serum levels of the proinflammatory cytokines (IL-6, IL-1 beta, and TNF-alpha), blood glucose, and lipid profiles were also regulated by GBE treatment. GBE might be beneficial in the treatment of diabetic myocardial injury.
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