Oben Jude A, Roskams Tania, Yang Shiqi, Lin Huizhi, Sinelli Nicoletta, Li Zhiping, Torbenson Michael, Huang Jiawen, Guarino Paul, Kafrouni Michel, Diehl Anna Mae
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Hepatology. 2003 Sep;38(3):664-73. doi: 10.1053/jhep.2003.50371.
Recovery from liver damage might be enhanced by encouraging repopulation of the liver by endogenous hepatic progenitor cells. Oval cells are resident hepatic stem cells that promote liver regeneration and repair. Little is known about the mediators that regulate the accumulation of these cells in the liver. Parasympathetic nervous system inhibition reduces the number of oval cells in injured livers. The effect of sympathetic nervous system (SNS) inhibition on oval cell number is not known. Adrenergic inhibition mobilizes hematopoietic precursors into the circulation and has also been shown to promote liver regeneration. Thus, we hypothesized that SNS inhibition would promote hepatic accumulation of oval cells and reduce liver damage in mice fed antioxidant-depleted diets to induce liver injury. Our results confirm this hypothesis. Compared with control mice that were fed only the antioxidant-depleted diets, mice fed the same diets with prazosin (PRZ, an alpha-1 adrenoceptor antagonist) or 6-hydroxydopamine (6-OHDA, an agent that induces chemical sympathectomy) had significantly increased numbers of oval cells. Increased oval cell accumulation was accompanied by less hepatic necrosis and steatosis, lower serum aminotransferases, and greater liver and whole body weights. Neither PRZ nor 6-OHDA affected the expression of cytokines, growth factors, or growth factor receptors that are known to regulate progenitor cells. In conclusion, stress-related sympathetic activity modulates progenitor cell accumulation in damaged livers and SNS blockade with alpha-adrenoceptor antagonists enhances hepatic progenitor cell accumulation.
通过促进内源性肝祖细胞在肝脏中的重新增殖，可能会增强肝脏损伤的恢复。卵圆细胞是驻留的肝干细胞，可促进肝脏再生和修复。关于调节这些细胞在肝脏中积聚的介质，人们了解甚少。副交感神经系统抑制会减少受损肝脏中卵圆细胞的数量。交感神经系统（SNS）抑制对卵圆细胞数量的影响尚不清楚。肾上腺素能抑制可将造血前体细胞动员到循环中，并且也已显示出可促进肝脏再生。因此，我们假设SNS抑制会促进卵圆细胞在肝脏中的积聚，并减少喂食抗氧化剂缺乏饮食以诱导肝损伤的小鼠的肝脏损伤。我们的结果证实了这一假设。与仅喂食抗氧化剂缺乏饮食的对照小鼠相比，喂食相同饮食并添加哌唑嗪（PRZ，一种α-1肾上腺素能受体拮抗剂）或6-羟基多巴胺（6-OHDA，一种诱导化学交感神经切除术的药物）的小鼠卵圆细胞数量显著增加。卵圆细胞积聚增加伴随着肝坏死和脂肪变性减少、血清转氨酶降低以及肝脏和体重增加。PRZ和6-OHDA均未影响已知调节祖细胞的细胞因子、生长因子或生长因子受体的表达。总之，与应激相关的交感神经活动调节受损肝脏中祖细胞的积聚，用α-肾上腺素能受体拮抗剂阻断SNS可增强肝祖细胞的积聚。
