摘要
目的:了解白介素-10(interleukin-10,IL-10)在骨髓间充质干细胞分泌的因子(mesenchymal stem cell-derived molecules,MSC-CM)逆转急性肝衰竭中的作用.方法:D-氨基半乳糖(D galactosamine,D-GaIN)和脂多糖(lipopolysaccharide,LPS)诱导建立Balb/c小鼠急性肝衰竭模型;贴壁筛选法培养纯化小鼠BMSCs和获得MSCCM.健康Balb/c小鼠♂随机均分为肝衰竭对照组、MSC-CM治疗组和MSC-CM+IL-10抗体组,每组18只.Kaplan-Meier法进行生存分析,生化检测各实验组丙氨酸转氨酶(alanine transaminase,ALT)和天冬氨酸转氨酶(aspartate aminotransferase,AST),36 h每组处死1-2只动物,取肝脏进行肝脏病理检测.ELISA检测血清高迁移率蛋白B1(high mobility group box 1,HMGB1)、IL-1、肿瘤坏死因子(tumor necrosis factor,TNF-)和IL-10水平.结果:MSC-CM治疗组1 wk生存率为88.9%,显著高于肝衰竭对照组的39%,P<0.01.12、24和48 h血清ALT和AST峰值显著低于肝衰竭对照组(P<0.01).36 h肝脏炎症坏死较对照明显减轻.MSC-CM治疗组在6、12和24 h HMGB1水平以及24 h的TNF-和IL-1水平显著低于肝衰竭对照组(P<0.01),而抗炎因子IL-10显著高于对照组(P<0.01).IL-10抗体阻断致MSCCM治疗的生存率降低和ALT水平升高,肝脏炎症坏死增加,血清HMGB1、TNF-和IL-1水平升高.结论:IL-10在MSC-CM逆转小鼠急性肝衰竭中发挥重要作用.
AIM： To explore the role of interleukin-10 （IL-10） in mediating the therapeutic effects of bone mar- row mesenchymal stem cell-derived molecules （MSC-DM） on acute live failure （ALF）. METHODS： D-galactosamine （D-GaIN） and lipopolysaccharide （LPS） were used to induce ALF in male BALB/c mice. Bone marrow MSCs were cultured and purified by the adherent method and medium containing MSC-CM was harvested. Healthy BALB/c mice were random- ly assigned to three groups （n = 18 for each）： ALF group, MSC-CM treatment group andMSC-CM plus IL-10 antibody group. Kaplan- Meier method was used for survival analysis. Serum alanine transaminase （ALT） and aspar- tate aminotransferase （AST） levels were detected at different time points, liver tissue pathological changes were examined after 24 h, and ihigh mo- bility group box 1 （HMGB1）, IL-1β, tumor necro- sis factor α （TNF-α） and IL-10 were det：ected by ELISA. RESULTS： The survival rate was significantly higher in the MSC-CM treatment group than in the ALF group （88.9% vs 39%, P 〈 0.01）. MSC- CM treatment decreased ALT/AST levels at12, 24 and 48 h more significantly compared with the ALF group （all P 〈 0.01）. Serum HMGB1 at 6, 12, and 24 h, and TNF-α and IL-1β at 24 h were also decreased significantly in the MSC-CM treatment group （all P 〈 0.01）, however, IL-10 level was increased significantly in the MSC- CM treatment group （P 〈 0.01）. The inflamma- tion and necrosis in liver tissues were mitigated more significantly in the MSC-CM treatment group than in the ALF group （P 〈 0.01）. In MSC-CM treated mice, administration of IL-10 antibody neutralized the therapeutic effects of MSC-CM： survival rate was decreased, and ALT level, serum HMGB1, TNF-α, IL-1β and inflammation or necrosis in liver tissues at 24 h were increased. CONCLUSION： IL-10 plays an important role in mediating the therapeutic effects of MSC-CM on ALF.
出处
《世界华人消化杂志》
CAS
北大核心
2013年第34期3783-3789,共7页
World Chinese Journal of Digestology
基金
江西省科技支撑基金资助项目
No.2009JX00916
南昌市科技局重点基金资助项目
No.洪财政[2012]37号社会发展支撑计划-10~~
