肝再生能力的丧失是老年性病理改变中最为显著的肝脏变化，提高肝脏的再生能力对老年肝病患者具有很好的治疗价值。前期发现激活自然杀伤T（NKT）细胞后可明显抑制2/3肝切除手术（PHx）导致的肝再生；另外还发现白细胞介素（IL-22）可促进原有或无肝疾患年轻小鼠的肝再生能力。然而NKT细胞在老年肝脏中数目功能改变、NKT对老年性肝再生的影响和IL-22是否可以促进老年性肝再生作用仍不甚明了。本课题拟采用经典的PHx模型、α-半乳糖神经酰胺特异性激活NKT细胞和NKT细胞基因敲除小鼠，研究NKT细胞在老年性肝再生中的作用；利用健康年轻人和老年人血液样本，检测NKT细胞数目、功能和IL-22水平差异；应用老年小鼠研究给予IL-22后是否能促进低下的老年性肝再生能力。本课题试图阐明NKT细胞在老年肝和老年性肝再生中的角色，为寻找新的安全的可能应用于治疗老年性肝病导致的肝再生能力不足的药物奠定基础。

The loss of regenerative capacity is the most dramatic age-related change in the aging liver. Improving liver regeneration presents a potential therapeutic target in old patients with liver diseases. Our previous work shows that activation of natural killer T (NKT) cells inhibits liver regeneration. Our recent findings demonstrate that interleukin 22(IL-22) is a key cytokine for accelerating liver regeneration in young mice with or without pre-damaged condition. However, the number and function changing of NKT cells in aging liver，effects of NKT cells on aging liver regeneration; and whether IL-22 can promote aging liver regeneration remain obscure. To characterize the role of NKT cells in aging liver regeneration and test the promotion effects of IL-22 on reduced aging hepatocyte proliferation. Partial hepatectomy (PHx) will be used to study liver regeneration. alpha-GalCer, a specific ligand for NKT cells, was used to induce NKT cell activation. The effects of NKT cells and IL-22 on aging liver regeneration will be assessed using different knockout and aged mice. The number and function of NKT cells will be determined by FACS method during aging in human and mice. Taken together, the current project will be important to characterize the role of NKT cells in the reduced aging liver regeneration and to determine if treatment with exogenous IL-22 or up-regulation of this proteins in vivo that can be used to stimulate liver regeneration under aging conditions. This objective may provide some evidence to developing a new safe IL-22 therapeutic strategy in aging liver diseases.