Adipose-derived stem cells alleviate liver apoptosis induced by ischemia-reperfusion and laparoscopic hepatectomy in swine.
Adipose-derived stem cells alleviate liver apoptosis induced by ischemia-reperfusion and laparoscopic hepatectomy in swine.
复制标题
脂肪干细胞减轻猪缺血再灌注和腹腔镜肝切除术诱导的肝细胞凋亡
DOI：
10.1038/s41598-018-34939-x
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发表时间：
2018-11-15
影响因子：
4.6
通讯作者：
Wang H
中科院分区：
文献类型：
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作者：
Ge Y;Zhang Q;Li H;Bai G;Jiao Z;Wang H
肝脏缺血再灌注（I/R）损伤是肝切除术中不可避免的，并可能导致术后并发症和死亡。再生医学认为脂肪干细胞（ADSCs）是治疗肝脏疾病的一种有吸引力的工具。在这项研究中，我们研究了脂肪干细胞在I/R模型结合腹腔镜肝切除术中的作用。将18头巴马小型猪随机分为假手术组（Sham）、缺血再灌注组（IRI）和脂肪干细胞组（ADSC）。半肝切除后即刻经肝实质注射ADSCs（1 × 106/kg）。研究脂肪干细胞的凋亡相关作用。结果表明，脂肪干细胞移植可减轻肝细胞的病理和超微结构改变，减少凋亡阳性细胞的数量。在ADSCs组中，Fas、Fas配体（FasL）蛋白和mRNA表达下调，Caspase 3、Caspase 8和Caspase 9酶活性显著降低。此外，ADSC治疗组Bcl-2/Bax蛋白和mRNA的比值明显高于IRI组。总之，脂肪干细胞减弱了猪模型中I/R和肝切除术诱导的肝细胞凋亡，并为肝I/R和肝切除术提供了潜在的治疗选择。
Hepatic ischemia-reperfusion (I/R) injury is inevitable during hepatectomy and may cause both postoperative morbidity and mortality. Regenerative medicine suggested adipose-derived stem cells (ADSCs) as an attractive tool for the treatment of liver diseases. In this study, we investigated the effect of ADSCs in an I/R model combined with laparoscopic hepatectomy in swine. Eighteen Bama miniature pigs were randomly divided into Sham, IRI, and ADSCs groups. ADSCs (1 × 106/kg) were injected through liver parenchyma immediately after hemihepatectomy. The apoptosis-related role of ADSCs was studied. The results showed that ADSCs transplantation reduced both pathological and ultrastructural changes and decreased the number of apoptotic-positive cells. In the ADSCs group, Fas, Fas ligand (FasL) protein, and mRNA were downregulated and the enzyme activities of Caspase3, Caspase8, and Caspase9 were significantly decreased. In addition, ADSC therapy significantly increased the ratio of Bcl-2/Bax protein and mRNA compared to the IRI group. In conclusion, ADSCs attenuated both I/R and hepatectomy-induced liver apoptosis in a porcine model, and offers a potential therapeutic option for hepatic I/R and hepatectomy.