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：22

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

来源：

MOLECULAR MEDICINE REPORTS | 2016年 / 13卷 / 02期

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 [肿瘤学];

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

页码：1211 / 1219

页数：9

共 58 条

[51]

Correlation between serum high-mobility group box-1 levels and high-sensitivity C-reactive protein and troponin I in patients with coronary artery disease [J].