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同种异体骨髓间充质干细胞通过抑制氧化应激和抑制细胞凋亡减轻大鼠肝缺血再灌注损伤。

Allogeneic bone marrow-derived mesenchymal stem cells attenuate hepatic ischemia-reperfusion injury by suppressing oxidative stress and inhibiting apoptosis in rats.

机构信息

Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People's Republic of China.

出版信息

Int J Mol Med. 2013 Jun;31(6):1395-401. doi: 10.3892/ijmm.2013.1340. Epub 2013 Apr 9.

DOI:10.3892/ijmm.2013.1340
PMID:23589072
Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been shown to attenuate ischemia reperfusion (IR) injury in the heart, brain and kidney. However, their exact roles in the liver remain to be defined. Our objective was to investigate the potential effects of BM-MSCs on a hepatic IR rat model during the first 24 h after reperfusion, a crucial period for hepatic IR damage formation. A rat model of normothermic partial hepatic ischemia was obtained by vascular clamping for 60 min. BM-MSCs were transplanted via portal vein injection. Injury severity, oxidative stress response and apoptosis of liver cells were assessed at 2, 6, 12 and 24 h after reperfusion and cell transplantation was evaluated. At 12 and 24 h after reperfusion, rats transplanted with BM-MSCs had significantly lower serum levels of alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST), fewer damaged liver tissues, higher superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and lower malondialdehyde (MDA) levels compared to rats in the sham transplantation group. At 24 h after reperfusion, IR rats transplanted with BM-MSCs had significantly fewer apoptotic hepatocytes, higher levels of B-cell lymphoma 2 (Bcl-2) protein, and lower levels of Bcl-2-associated X (Bax) and caspase-3 (Casp3) proteins compared to sham transplantation rats. In conclusion, BM-MSCs transplanted via the portal vein partially prevent hepatic IR injury by suppressing oxidative stress and inhibiting apoptosis during the first 24 h after reperfusion.

摘要

骨髓间充质干细胞(BM-MSCs)已被证明可减轻心脏、大脑和肾脏的缺血再灌注(IR)损伤。然而,它们在肝脏中的确切作用仍有待确定。我们的目的是在再灌注后 24 小时内研究 BM-MSCs 对肝 IR 大鼠模型的潜在影响,这是肝 IR 损伤形成的关键时期。通过血管夹闭获得常温下部分肝缺血的大鼠模型,夹闭 60 分钟。通过门静脉注射移植 BM-MSCs。在再灌注和细胞移植后 2、6、12 和 24 小时评估损伤严重程度、氧化应激反应和肝细胞凋亡,并评估细胞移植情况。在再灌注后 12 和 24 小时,与 sham 移植组相比,移植 BM-MSCs 的大鼠血清丙氨酸转氨酶(ALT)和血清天冬氨酸转氨酶(AST)水平显著降低,受损肝组织减少,超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性更高,丙二醛(MDA)水平更低。再灌注后 24 小时,与 sham 移植大鼠相比,移植 BM-MSCs 的 IR 大鼠的凋亡肝细胞更少,B 细胞淋巴瘤 2(Bcl-2)蛋白水平更高,Bcl-2 相关 X(Bax)和半胱天冬酶-3(Casp3)蛋白水平更低。总之,门静脉移植的 BM-MSCs 通过在再灌注后 24 小时内抑制氧化应激和抑制细胞凋亡,部分预防肝 IR 损伤。

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