Intravenous high mobility group box 1 upregulates the expression of HIF-1α in the myocardium via a protein kinase B-dependent pathway in rats following acute myocardial ischemia

被引:17
作者
Yao, Heng-Chen [1 ,2 ]
Zhou, Min [2 ]
Zhou, Yan-Hong [2 ]
Wang, Lan-Hua [2 ]
Zhang, De-Yong [2 ]
Han, Qian-Feng [2 ]
Liu, Tao [2 ]
Wu, Lei [2 ]
Tian, Ke-Li [3 ]
Zhang, Mei [1 ]
机构
[1] Shandong Univ, Sch Med, Qilu Hosp, Dept Cardiol, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China
[2] Taishan Med Univ, Liaocheng Peoples Hosp & Clin Sch, Dept Cardiol, Liaocheng 252000, Shandong, Peoples R China
[3] Shandong Univ, Sch Med, Dept Biochem & Mol Biol, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China
关键词
high mobility group box 1; acute myocardial ischemia; ischemia reperfusion injury; hypoxia inducible factor-1 alpha; rats; INDUCIBLE FACTOR-I; ENDOTHELIAL GROWTH-FACTOR; CORONARY-ARTERY-DISEASE; REPERFUSION INJURY; OXIDATIVE STRESS; ISCHEMIA/REPERFUSION INJURY; POSTCONDITIONING PROTECTS; INTERMITTENT HYPOXIA; HEART; APOPTOSIS;
D O I
10.3892/mmr.2015.4648
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The effects of intravenous high mobility group box 1 (HMGB1) on myocardial ischemia/reperfusion (I/R) injury remains to be elucidated. The purpose of the present study was to investigate the effects of intravenous HMGB1 on the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha) in the myocardium of rats following acute myocardial ischemia, and to examine the effects of intravenous HMGB1 on myocardial ER injury. Male Wistar rats were divided into the following groups: Sham operation group (n=10), a group exposed to ischemia for 30 min and reperfusion for 4 h (PR group) as a control (n=10), an HMGB group, in which 100 ng/kg HMGB was administered intravenously 30 min prior to ischemia (n=110), an LY group, in whic LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), was administered intravenously (0.3 mg/kg) 40 min prior to ischemia (n=10), and the HMGRI+LY group, in which HMGR1 (100 ng/kg) and LY294002 (0.3 mg/kg) were administered intravenously 30 min and 40 min prior to ischemia, respectively (n=10). The serum levels of cardiac troponin I (cInI) and tumor necrosis factor-alpha (TNF-alpha), and myocardial infarct size were measured. The expression levels of phosphorylated Akt and HIP-1 alpha were investigated using western blot analyses. The results showed that pre-treatment with HMGB1 significantly decreased serum levels of cInI, and INF-alpha, and reduced myocardial infarct size following 4 h reperfusion (all P<0.05). HMGB1 also increased the expression levels of HIP-1 alpha and p-Akt induced by I/R (P<0.05). LY294002 was found to eliminate the effects of intravenous HMGB1 on myocardial I/R injury (P<0.05). These results suggest that intravenous pre-treatment with HMGB1 may exert its cardioprotective effects via the upregulation of the myocardial expression of HIF-1 alpha, which may he regulated by the PI3K/Akt signaling pathway, in rats following acute myocardial I/R.
引用
收藏
页码:1211 / 1219
页数:9
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