Dexmedetomidine Alleviates Myocardial Ischemia-Reperfusion Injury through Mitochondrial and ER Oxidative Stress Pathways
Dexmedetomidine Alleviates Myocardial Ischemia-Reperfusion Injury through Mitochondrial and ER Oxidative Stress Pathways
Min Li1, Shiwu Deng2*, Yiqian Peng3 and Hong Li2
ABSTRACT
The objective of this study was to explore the mechanism by which dexmedetomidine (DEX) alleviates myocardial ischemia-reperfusion injury (MIRI) through mitochondrial and ER oxidative stress pathways. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) of SD rats were measured by echocardiography, and the mRNA expression level of peroxisome proliferator-activated receptor gamma co-activator 1-a (PGC1 a), superoxide dismutase (SOD2) and citrate synthase (Cs) were detected by real-time PCR. Ultrastructural changes of myocardial mitochondria were observed by transmission electron microscope. The activity of Caspase-3 in heart tissue of SD rats was measured, and the expression of p-JNK, GRP78, Caspase 12 and CHOP in heart tissue of SD rats was determined by Western blot. We found that LVEDd and LVESd in MIRI group and MIRI + DEX group were significantly higher than those in sham operation group (P<0.05), and LVEF was significantly lower than that in sham operation group (P<0.05). Compared with MIRI group, the expression levels of PGC1-a, SOD2 and Cs genes in MIRI + DEX group were significantly lower(P<0.05), and mitochondrial structure was slightly damaged in MIRI + DEX group. Compared with the sham operation group, p-JNK, Caspase 12, CHOP and GRP78 in MIRI group and MIRI + DEX group increased significantly (P<0.05), Compared with MIRI group, the expression of p-JNK, Caspase-12 and CHOP protein in MIRI + DEX group decreased significantly (P<0.05), while the expression of GRP78 increased (P<0.05). It is concluded DEX can alleviate mitochondrial damage induced by ischemia reperfusion, inhibit excessive endoplasmic reticulum and improve myocardial function.
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