Department of Anesthesiology, The First Affiliated Hospital, Henan Science and Technology University, Luoyang, Henan, China.
J Surg Res. 2014 Jan;186(1):240-5. doi: 10.1016/j.jss.2013.07.052. Epub 2013 Aug 19.
Dexmedetomidine (DEX) has been shown to decrease ischemia-reperfusion (I/R) injury in kidney and brain tissues. In this study, the effects of DEX were evaluated in skeletal muscle during I/R injury.
Animals were divided into four groups: sham-operated (sham group), saline + I/R, DEX + I/R, and α-tocopherol + I/R groups. Hind limb ischemia was induced by clamping the common femoral artery and vein. After 4 h of ischemia, the clamp was removed and the animals underwent 2 h of reperfusion. Animals in the drug treatment group received DEX or α-tocopherol by intraperitoneal injection 1 h before reperfusion. We measured plasma concentrations of interleukin 1β and tumor necrosis factor α levels using an enzyme-linked immunosorbent assay. The right gastrocnemius muscle was harvested and immediately stored at -80°C for the assessment of superoxide dismutase (SOD) and catalase (CAT) activities as well as glutathione (GSH), malondialdehyde (MDA), and protein oxidation (PO) levels. DEX (25 μg/kg) and normal saline (10 mL/kg) were administered by intraperitoneal injection 1 h before reperfusion.
Plasma tumor necrosis factor α or interleukin 1β levels increased significantly in the I/R group (P < 0.01 compared with sham group) and decreased significantly in the DEX group (P < 0.01 compared with I/R group). Muscle tissues of the I/R group had significantly decreased SOD, GSH, and CAT activities and increased levels of MDA and PO content compared with the sham group. The activity of antioxidant enzymes in the DEX + I/R group was greatly elevated compared with that in the I/R group (SOD, 1.068 ± 0.120 versus 0.576 ± 0.072 U/mg protein; GSH, 2.436 ± 0.144 versus 1.128 ± 0.132 μmol/g; and CAT, 69.240 ± 6.456 versus 31.884 ± 6.312 U/mg protein; P < 0.01), whereas the levels of MDA and PO content were clearly reduced (23.268 ± 3.708 versus 53.604 ± 5.972 nmol/g protein and 1.908 ± 0.192 versus 5.208 ± 0.612 nmol/mg protein, respectively; P < 0.01). Moreover, DEX exhibited more potent antioxidant activity than vitamin E in the skeletal muscle I/R.
We found that DEX exhibits protective effects against skeletal muscle I/R injury. These results underscore the necessity of human studies with DEX to determine if it is beneficial for preventing skeletal muscle I/R injury.
右美托咪定(DEX)已被证明可减少肾和脑组织的缺血再灌注(I/R)损伤。在这项研究中,评估了 DEX 在骨骼肌 I/R 损伤中的作用。
动物分为四组:假手术(sham 组)、盐水+I/R、DEX+I/R 和α-生育酚+I/R 组。通过夹闭股总动脉和静脉诱导后肢缺血。缺血 4 小时后,松开夹闭,动物再灌注 2 小时。药物治疗组动物在再灌注前 1 小时通过腹腔注射接受 DEX 或α-生育酚。我们使用酶联免疫吸附测定法测量血浆白细胞介素 1β和肿瘤坏死因子α水平。右腓肠肌组织收获后立即储存在-80°C 下,用于评估超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性以及谷胱甘肽(GSH)、丙二醛(MDA)和蛋白氧化(PO)水平。DEX(25μg/kg)和生理盐水(10mL/kg)在再灌注前 1 小时通过腹腔注射给予。
与 sham 组相比,I/R 组的血浆肿瘤坏死因子α或白细胞介素 1β水平显著升高(P<0.01),DEX 组显著降低(P<0.01)。与 sham 组相比,I/R 组的肌肉组织 SOD、GSH 和 CAT 活性显著降低,MDA 和 PO 含量水平显著升高。与 I/R 组相比,DEX+I/R 组的抗氧化酶活性显著升高(SOD,1.068±0.120 对 0.576±0.072 U/mg 蛋白;GSH,2.436±0.144 对 1.128±0.132 μmol/g;CAT,69.240±6.456 对 31.884±6.312 U/mg 蛋白;P<0.01),而 MDA 和 PO 含量水平明显降低(23.268±3.708 对 53.604±5.972 nmol/g 蛋白和 1.908±0.192 对 5.208±0.612 nmol/mg 蛋白;P<0.01)。此外,DEX 在骨骼肌 I/R 中表现出比维生素 E 更强的抗氧化活性。
我们发现 DEX 对骨骼肌 I/R 损伤具有保护作用。这些结果强调了用 DEX 进行人体研究的必要性,以确定它是否有益于预防骨骼肌 I/R 损伤。