脐血NK细胞改善亚急性衰老大鼠肝脏损伤  

Umbilical cord blood NK cells improved liver injury in sub-acute aging rats

作　　者：兰静 李栋[2] 时庆[2] 刘子琳 周盼盼[1] 鞠秀丽[1,2] LAN Jing;LI Dong;SHI Qing;LIU Zilin;ZHOU Panpan;JU Xiuli(Department of Pediatrics,Qilu Hospital of Shandong University,Jinan 250012,Shandong,China;Stem Cell and Regenerative Medicine Research Center of Shandong University,Jinan 250012,Shandong,China)

机构地区：[1]山东大学齐鲁医院儿科,山东济南250012 [2]山东大学干细胞与再生医学研究中心,山东济南250012

出　　处：《山东大学学报（医学版）》2018年第10期64-71,共8页Journal of Shandong University:Health Sciences

基　　金：山东省重点研发计划(2017GSF18115;2017GSF218015);济南市科技发展计划(201704066);山东省自然科学基金(2014ZRE27630;ZR2014HP037)

摘　　要：目的探讨脐血NK细胞改善亚急性衰老大鼠模型肝脏损伤的可行性及其分子机制。方法采用基因工程改造的K562细胞,从新鲜脐带血获得大量NK细胞。8～10周龄雄性Wistar大鼠随机分为4组:Normal组、Model组、Mod-Con组和Mod-NK组。实验完成1周后观察大鼠体质量及肝脏指数,检测血清和肝脏中超氧化物岐酶(SOD)、丙二醛(MDA)及肝脏中凋亡相关基因的表达,观察肝脏切片组织细胞形态变化。结果皮下注射D-半乳糖可成功构建亚急性衰老大鼠模型。输注大量高纯度的脐血NK细胞,可显著改善其肝脏损伤,促进体质量回升(P <0. 01)并降低肝脏指数(P <0. 05),血清及肝脏中SOD活性增强(P <0. 01),MDA水平降低(P <0. 01);肝脏切片示肝细胞水肿减轻,Masson染色显示肝组织纤维化减轻;促凋亡基因表达减少(P <0. 01),而抗凋亡基因成纤维细胞生长因子表达上升(P <0. 01)。结论脐血NK细胞输注可有效改善亚急性衰老大鼠的肝脏损伤。Objective To investigate the feasibility and molecular mechanism of umbilical cord blood NK cells in improving liver injury in sub-acute aging rat models.Methods NK cells in cord blood (CB)were amplified from fresh CB mononuclear cells using genetically engineered K562cells.Male Wistar rats aged 8-10 weeks were randomly divided into four groups :Normal group,Model group,Mod-Con group and Mod-NK group.Body weight and liver index,superoxide dismutase (SOD)and malondialdehyde (MDA)levels in serum and liver,and genes related to apoptosis were tested one week after the experiment.The morphology of liver sections was observed.Results Sub-acute aging rat models could be constructed successfully by subcutaneous injection of D-galactose.The transfusion of high-purity and high-concentration NK cells could significantly promote the recovery of liver injury and body weight (P<0.01),decrease the liver index (P<0.05),enhance the SOD activity (P<0.01),and reduce the level of MDA in serum and liver tissues (P<0.01).The liver sections showed that hepatic edema relieved.Masson staining indicted that fibrosis of liver decreased.Expression of apoptosis promoting genes decreased (P<0.01),while antiapoptotic gene and fibroblast growth factor increased (P<0.01).Conclusion Transfusion of umbilical cord blood NK cells can effectively improve the liver injury in sub-acute aging rats.

关 键 词：自然杀伤细胞 亚急性衰老 抗衰老 肝脏损伤 

分 类 号：R332[医药卫生—人体生理学]