骨髓间充质干细胞通过修复肠肝屏障和激活肝细胞生长因子缓解溃疡性结肠炎所致肝损伤。
BMSC cells alleviate liver injury induced by ulcerative colitis via repairing the intestinal-liver barrier and activating hepatocyte growth factor.
机构信息
Guangxi Medical University, Nanning 530021, China.
Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin 541002, China.
出版信息
Cell Mol Biol (Noisy-le-grand). 2023 Feb 28;69(2):19-25. doi: 10.14715/cmb/2022.69.2.4.
Ulcerative colitis (UC), which belongs to inflammatory bowel diseases (IBD), frequently induces liver inflammation and injury. Previous studies have proved that bone marrow-derived mesenchymal stem cells (BMSCs) can suppress inflammation and improve intestinal mucosal injury in colitis, however, the effects of BMSCs on colitis-induced liver injury and the underlying molecular mechanisms remain unclear. Here, we investigated the effects and mechanisms of BMSCs in acute ulcerative colitis BALB/c mice, which were induced by 4 % dextran sodium sulphate (DSS). In this study, BMSCs derived from BALB/c mice were administrated by single intravenous injection with a dose of 5*10^7 cells/kg. And then, the effects and underlying molecular mechanisms were investigated. Firstly, the degree of liver injury in colitis mice was evaluated by hepatic ALT, AST, ALP and TBIL levels, which were measured by specific determination kits, the levels of TNF-α, IL-6, IFNγ and LPS were examined by ELISA. Secondly, as the indicator of intestinal-liver barrier disorder, tight junction proteins were analyzed by western blot. Thirdly, the pathological changes in the colon and liver were detected by H&E staining. At last, homing of BMSCs to lesion tissues was investigated by Immunofluorescence. The results indicated that histopathological changes in model mice had been greatly alleviated, BMSCs infusion remarkably decreased the serum ALT, AST, ALP and TBIL levels, and meanwhile reduced pro-inflammatory cytokines in liver tissues. Furthermore, homing of BMSCs was observed in the colon and liver, and the disorder of the intestinal-liver barrier declined significantly. In conclusion, BMSCs alleviate liver injury induced by ulcerative colitis via repairing the intestinal-liver barrier and activating hepatocyte growth factor, it has potential application prospects in the treatment of liver injury induced by ulcerative colitis.
溃疡性结肠炎（UC）属于炎症性肠病（IBD），常引起肝脏炎症和损伤。先前的研究已经证明骨髓间充质干细胞（BMSCs）可以抑制结肠炎中的炎症并改善肠道黏膜损伤，然而，BMSCs 对结肠炎诱导的肝损伤的影响及其潜在的分子机制仍不清楚。在这里，我们研究了 BMSCs 在由 4%葡聚糖硫酸钠（DSS）诱导的急性溃疡性结肠炎 BALB/c 小鼠中的作用和机制。在这项研究中，通过单次静脉注射给予 BALB/c 小鼠来源的 BMSCs，剂量为 5*10^7 个细胞/kg。然后，研究了其作用和潜在的分子机制。首先，通过特定的测定试剂盒测量肝 ALT、AST、ALP 和 TBIL 水平来评估结肠炎小鼠的肝损伤程度，通过 ELISA 检测 TNF-α、IL-6、IFNγ和 LPS 水平。其次，通过 Western blot 分析紧密连接蛋白作为肠肝屏障紊乱的指标。第三，通过 H&E 染色检测结肠和肝脏的病理变化。最后，通过免疫荧光法研究 BMSCs 向病变组织的归巢。结果表明，模型小鼠的组织病理学变化得到了极大缓解，BMSCs 输注显著降低了血清 ALT、AST、ALP 和 TBIL 水平，同时减少了肝组织中的促炎细胞因子。此外，观察到 BMSCs 在结肠和肝脏中的归巢，肠肝屏障的紊乱明显改善。总之，BMSCs 通过修复肠肝屏障和激活肝细胞生长因子来减轻溃疡性结肠炎引起的肝损伤，在治疗溃疡性结肠炎引起的肝损伤方面具有潜在的应用前景。
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