1. Department of Stem Cell Disorders, Kansai Medical University, Hirakata City, Osaka, Japan.
2. Department of Cardiac Surgery, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China.
Int J Biol Sci. 2015 Mar 19;11(4):472-81. doi: 10.7150/ijbs.10809. eCollection 2015.
Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance, oxidative stress, and obesity. The db/db mouse model displays increased levels of insulin resistance, obesity, and an over-accumulation of hepatic triglycerides, making it an excellent model for studying NAFLD. In db/db mice, intra-bone marrow-bone marrow transplantation plus thymus transplantation (IBM-BMT+TT) improves type 2 diabetes mellitus (T2 DM) by normalizing the T-cell imbalance. We hypothesized that this approach would improve Sirt1 expression in the liver and benefit liver development. The db/db mice were treated with IBM-BMT+TT, and plasma MCP-1, IL-6, adiponection, LDL, Sirt1, and HO-1 levels were then assessed. Stem cell transplantation decreased the levels of plasma inflammatory cytokines and LDL while it increased the expression of Sirt1 and HO-1, resulting in decreased progression of fatty liver. Moreover, Sirt1 and HO-1 expression were both detected in the thymus and many HO-1-positive cells were observed in the bone marrow. This is the first report of stem cell transplantation improving the antioxidant function in the liver, thymus, and bone marrow of db/db mice by increasing the levels of Sirt1 and HO-1. This approach may prove useful in the treatment of nonalcoholic steatohepatitis and its clinical manifestations.
非酒精性脂肪性肝病（NAFLD）与胰岛素抵抗、氧化应激和肥胖有关。db/db 小鼠模型表现出胰岛素抵抗、肥胖和肝内甘油三酯过度积累增加，使其成为研究 NAFLD 的理想模型。在 db/db 小鼠中，骨髓内骨髓移植加胸腺移植（IBM-BMT+TT）通过使 T 细胞失衡正常化来改善 2 型糖尿病（T2DM）。我们假设这种方法可以改善肝脏中的 Sirt1 表达并有益于肝脏发育。对 db/db 小鼠进行 IBM-BMT+TT 治疗，然后评估血浆 MCP-1、IL-6、脂联素、LDL、Sirt1 和 HO-1 水平。干细胞移植降低了血浆炎性细胞因子和 LDL 的水平，同时增加了 Sirt1 和 HO-1 的表达，从而减缓了脂肪肝的进展。此外，在胸腺和骨髓中均检测到 Sirt1 和 HO-1 的表达，并且在骨髓中观察到许多 HO-1 阳性细胞。这是首例报道干细胞移植通过增加 Sirt1 和 HO-1 水平来改善 db/db 小鼠肝脏、胸腺和骨髓的抗氧化功能。这种方法可能对治疗非酒精性脂肪性肝炎及其临床表现有用。
