经肝动脉同种异体脂肪干细胞移植治疗小鼠自身免疫性肝炎的实验研究

目的: 探讨同种异体脂肪干细胞经肝动脉移植对刀豆素A(Con A)诱导的小鼠自身免疫性肝炎的治疗价值。方法: Con A注射法建立小鼠自身免疫性肝炎模型。将40只小鼠随机分为4组:阴性对照组、经肝动脉移植组、经尾静脉移植组(移植脂肪干细胞2×10⁶)和阳性对照组。阳性对照组应用环磷酰胺腹腔注射。观察移植前后肝脏组织病理病变情况、血清炎症指标和肝功能指标的改变。结果: 经肝动脉移植组和经尾静脉移植组行脂肪干细胞移植后全部存活,未发生明显并发症;经肝动脉移植组血清炎症指标(IFN-γ、IL-4和IL-5)及血清天冬氨酸氨基转移酶、丙氨酸氨基转移酶及碱性磷酸酶明显下降(P<0.05);经尾静脉移植组血清炎症指标及血清肝功能指标有所下降,但无显著差异。经肝动脉移植组及阳性对照组病理学上改善最明显,肝内炎症细胞浸润及肝细胞坏死均明显减少。结论: 同种异体脂肪干细胞移植有助于改善Con A介导的小鼠自身免疫性肝炎,经肝动脉途径可提高脂肪干细胞肝移植的效能。

Treatment of Con A-induced autoimmune hepatitis with hepatic artery transplantation of allogeneic ADSCs in mice

AIM: To explore the therapeutic potential of adipose tissue-derived stem cell (ADSC) transplantation via hepatic artery in concanavalin A(Con A)-induced autoimmune hepatitis in mice. METHODS: Forty mice with Con A-induced hepatitis were randomly divided into 4 groups: negative group, hepatic artery group, caudal vein,group and positive control group. The mice in hepatic artery group and caudal group were transplanted with ADSCs (2×10⁶) via hepatic artery and caudal vein, respectively. Cyclophosphamide injection was taken as positive control. Inflammatory cytokines involved in Con A-induced hepatitis, liver function index, manifestations and pathological changes of the liver were observed before and after treatment. RESULTS: All animals survived after ADSC transplantation in hepatic artery group and caudal vein group. Compared with caudal vein transplantation group, ADSC transplantation via hepatic artery significantly reduced the release of inflammatory cytokines (IFN-γ,IL-4 and IL-5), and the serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. Pathological changes of the livers showed that the extent of inflammatory infiltration after hepatic artery transplantation of ADSCs was similar to that in positive control group. The inflammatory cells and necrosis of hepatic cells were significantly reduced compared with those in caudal vein group. CONCLUSION: Transplantation of allogeneic ADSCs via hepatic artery attenuates Con A-induced autoimmune hepatitis in mice. ADSC transplantation may be the potential therapy for autoimmune hepatitis.