College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, P.R. China.
Sci Rep. 2018 Nov 15;8(1):16878. doi: 10.1038/s41598-018-34939-x.
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 × 10/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.
肝缺血再灌注（I/R）损伤是肝切除术过程中不可避免的，可能导致术后发病率和死亡率。再生医学提出脂肪来源的干细胞（ADSCs）作为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 ADSCs 在猪的 I/R 模型结合腹腔镜肝切除术的影响。18 头巴马小型猪随机分为假手术组、IRI 组和 ADSCs 组。ADSCs（1×106/kg）在半肝切除术后立即通过肝实质注射。研究了 ADSCs 的凋亡相关作用。结果表明，ADSCs 移植减少了病理和超微结构变化，减少了凋亡阳性细胞的数量。在 ADSCs 组中，Fas、Fas 配体（FasL）蛋白和 mRNA 下调，Caspase3、Caspase8 和 Caspase9 的酶活性显著降低。此外，ADSC 治疗与 IRI 组相比，显著增加了 Bcl-2/Bax 蛋白和 mRNA 的比值。总之，ADSCs 减轻了猪模型中的 I/R 和肝切除引起的肝细胞凋亡，为肝 I/R 和肝切除术提供了一种潜在的治疗选择。
