Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway.
Effects of Dexmedetomidine Postconditioning on Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Role of the PI3K/Akt-Dependent Signaling Pathway.
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DOI：
10.1155/2018/3071959
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发表时间：
2018
影响因子：
4.3
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Cheng X;Hu J;Wang Y;Ye H;Li X;Gao Q;Li Z
本研究旨在确定右美托咪定（DEX）是否对糖尿病心脏I/R损伤具有心脏保护作用及其机制。 将30只高糖高脂饮食和链脲佐菌素（STZ）诱导的糖尿病大鼠随机分为5组：糖尿病假手术组（DM-S）、糖尿病I/R组（DM-I/R）、糖尿病DEX组（DM-D）、糖尿病DEX +麦芽汁组（DM-DW）和糖尿病麦芽汁组（DM-W）。另取12只年龄匹配的雄性SD大鼠，随机分为假手术组（S）和缺血再灌注组（I/R）。除假手术组外，其余各组均行心肌缺血30 min再灌注120 min。于再灌注结束时取血浆测定丙二醛（MDA）、肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）含量及超氧化物歧化酶（SOD）活性。HE染色观察心肌组织病理变化。Western blot法检测Akt和GSK-3β蛋白的总表达和磷酸化表达。逆转录-聚合酶链反应（RT-PCR）检测Bcl-2/Bax mRNA水平的比值。 DEX能显著降低心肌缺血再灌注后血浆CK-MB、MDA含量和LDH水平，提高SOD活性。与I/R组相比，DEX组Akt和GSK-3β磷酸化水平升高，Bcl-2 mRNA表达升高，Bcl-2/Bax比值升高，Bax mRNA表达降低，而Wort后处理可减轻DEX的作用。 本研究结果提示，DEX后处理可能通过激活PI 3 K/Akt信号通路，增加GSK-3β的磷酸化，抑制心肌细胞凋亡和氧化应激，从而对糖尿病大鼠心肌I/R损伤起到保护作用。
The present study was designed to determine whether dexmedetomidine (DEX) exerts cardioprotection against myocardial I/R injury in diabetic hearts and the mechanisms involved. A total of 30 diabetic rats induced by high-glucose-fat diet and streptozotocin (STZ) were randomly assigned to five groups: diabetic sham-operated group (DM-S), diabetic I/R group (DM-I/R), diabetic DEX group (DM-D), diabetic DEX + Wort group (DM-DW), and diabetic Wort group (DM-W). Another 12 age-matched male normal SD rats were randomly divided into two groups: sham-operated group (S) and I/R group (I/R). All rats were subjected to 30 min myocardial ischemia followed by 120 min reperfusion except sham groups. Plasmas were collected to measure the malondialdehyde (MDA), creatine kinase isoenzymes (CK-MB), and lactate dehydrogenase (LDH) levels and superoxide dismutase (SOD) activity at the end of reperfusion. Pathologic changes in myocardial tissues were observed by H-E staining. The total and phosphorylated form of Akt and GSK-3β protein expressions were measured by western blot. The ratio of Bcl-2/Bax at mRNA level was detected by reverse transcription-polymerase chain reaction (RT-PCR). DEX significantly reduced plasma CK-MB, MDA concentration, and LDH level and increased SOD activity caused by I/R. The phosphorylation of Akt and GSK-3β was increased, Bcl-2 mRNA and the Bcl-2/Bax ratio was increased, and Bax mRNA was decreased in the DEX group as compared to the I/R group, while posttreatment with Wort attenuated the effects induced by DEX. The results of this study suggest that DEX postconditioning may increase the phosphorylation of GSK-3β by activating the PI3K/Akt signaling pathway and may inhibit apoptosis and oxidative stress of the myocardium, thus exerting protective effects in diabetic rat hearts suffering from I/R injury.
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影响因子：
37.8
作者：
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