背景:由于其抗炎和抗纤维化作用,已报道了岩藻黄质(Fx)在肝病中的有效性。基于间充质干细胞(MSC)的治疗也被提出作为肝纤维化治疗的有希望的策略。最近的研究表明,MSCs和药物的共同给药对肝纤维化具有明显的作用。
目的:本研究旨在确定胎盘来源的MSCs(PD-MSCs)与Fx联合治疗肝纤维化的治疗潜力,并评估其对肝纤维化发病机制主要环节的影响。
方法:PD-MSCs分离鉴定后,将近交ICR/CD1小鼠分为5组:对照组,CCl4组(CCl4),Fx组(CCl4+Fx),PD-MSCs组(CCl4+MSCs)和共治疗组(CCl4+MSCs+Fx)。进行了生化组织病理学研究。α-平滑肌肌动蛋白(α-SMA+)的半定量分析,基质金属蛋白酶(MMP-9+,MMP-13+),基质金属蛋白酶-1(TIMP-1+)区域的组织抑制剂,并通过免疫组织化学染色研究其中的阳性细胞数。转化生长因子-β(TGF-β),肝生长因子(HGF),使用酶免疫测定法测定肝匀浆中的前胶原1(COL1α1)和血清中的促炎细胞因子。
结果:与PD-MSCs或Fx的单一治疗相比,联合用药显著降低肝酶活性,肝纤维化的严重程度,促炎细胞因子水平,TGF-β水平,α-SMA+,TIMP-1+区域和其中的阳性细胞数,HGF水平升高,MMP-13+,和MMP-9+区域。
结论:Fx增强了PD-MSCs在CCl4诱导的肝纤维化中的治疗潜力,但需要更多的研究来了解PD-MSCs和Fx的相互影响。
BACKGROUND: The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy has also been proposed as a promising strategy for liver fibrosis treatment. Recent studies have shown that the co-administration of MSCs and drugs demonstrates a pronounced effect on liver fibrosis.
OBJECTIVE: This study aimed to determine the therapeutic potential of placenta-derived MSCs (PD-MSCs) in combination with Fx to treat liver fibrosis and evaluate their impact on the main links of liver fibrosis pathogenesis.
METHODS: After PD-MSCs isolation and identification, outbred ICR/CD1 mice were divided into five groups: Control group, CCl4 group (CCl4), Fx group (CCl4+Fx), PD-MSCs group (CCl4+MSCs) and cotreatment group (CCl4+MSCs+Fx). Biochemical histopathological investigations were performed. Semiquantitative analysis of the alpha-smooth muscle actin (α-SMA+), matrix metalloproteinases (MMP-9+, MMP-13+), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1+) areas, and the number of positive cells in them were studied by immunohistochemical staining. Transforming growth factor-beta (TGF-β), hepatic growth factor (HGF), procollagen-1 (COL1α1) in liver homogenate and proinflammatory cytokines in blood serum were determined using an enzyme immunoassay.
RESULTS: Compared to the single treatment with PD-MSCs or Fx, their combined administration significantly reduced liver enzyme activity, the severity of liver fibrosis, the proinflammatory cytokine levels, TGF-β level, α-SMA+, TIMP-1+ areas and the number of positive cells in them, and increased HGF level, MMP-13+, and MMP-9+ areas.
CONCLUSIONS: Fx enhanced the therapeutic potential of PD-MSCs in CCl4-induced liver fibrosis, but more investigations are necessary to understand the mutual impact of PD-MSCs and Fx.