摘要
目的:探讨同种异体骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)对急性肝衰竭动物高迁移率族蛋白B1(high mobility group Box1,HMGB1)的影响.方法:D-氨基半乳糖(D-GaIN)和脂多糖(LPS)诱导建立小鼠急性肝衰竭模型;贴壁筛选法培养纯化Balb/c小鼠BMSCs,传至第4代使用.90只健康Balb/c小鼠随机均分为3组:正常组、肝衰竭组、BMSCs治疗组.分别于12、24、48h检测各实验组ALT/AST水平,48h取各组肝脏行病理学检查.Western blot检测动物血清HMGB1含量.结果:急性肝功能衰竭小鼠经BMSCs移植治疗后生存率为83.3%,与肝衰竭组小鼠存活率16.7%相比差异有显著性意义(P<0.05).肝衰竭组与BMSCs治疗组12hALT/AST水平显著上升,24h达到高峰,48h开始下降,肝衰竭组与BMSCs治疗组12、24、48hALT/AST水平显著高于正常组(P<0.01),BMSCs治疗组12、24、48hALT/AST水平明显低于肝衰竭组,差异有显著性意义(P<0.05).肝脏组织病理学结果显示BMSCs治疗组肝细胞变性及坏死程度以及炎症浸润程度轻于肝衰竭组.免疫印迹显示,正常组血清中测不到HMGB1,肝衰竭组血清中HMGB1的含量显著高于BMSCs移植组血清中HMGB1的含量(P<0.01).结论:BMSCs移植能够抑制肝衰竭中HMGB1水平,BMSCs通过抑制HMGB1减轻肝脏炎症反应治疗急性肝衰竭,降低肝衰竭死亡率.
AIM： To explore the influence of allogeneic bone marrow mesenchymal stem cell （BMSC） transpantion on serum levels of high group box protein B1 （HMGB1） in an animal model of acute live failure （ALF）. METHODS： Balb/c mice were given D-galactosamine （D-GaIN） and lipopolysaccharide （LPS） to induce acute liver failure. BMSCs were cultured and purified. Ninety healthy Balb/c mice were randomly assigned to three groups： normal control group, ALF group, and BMSC treatment group. ALT/AST levels were tested 12, 24, and 48 h after treatment, and liver tissue pathological examination was performed after 48 h. The expression of HMGB1 in serum was detected by Western blot. RESULTS： The survival rate was significantly higher in the BMSC treatment group than in the ALF group （83.3% vs 16.7%, P 〈 0.05）. AST/ALT levels in the ALF group and BMSC treatment group rose significantly at 12 h, peaked at 24 h, and began to fall at 48 h. ALT/AST levels at 12, 24 and 48 h were significantly higher in the ALF group and BMSC treatment group than in the normal group （all P 〈 0.01）, and in the ALF group than in the BMSC treatment group （all P 〈 0.01）. The degeneration and necrosis in liver tissue were less obvious in the BMSC treatment group than in the ALF group. HMGB1 was almost not detectable in normal mouse serum. Serum levels of HMGB1 were significantly higher in the ALF group than in the BMSC treatment group （P 〈 0.01）. CONCLUSION： BMSC transplantation inhibits HMGB1 expression, reduces liver inflammation, and thereby lowers mortality in mice with ALF.
出处
《世界华人消化杂志》
CAS
北大核心
2012年第16期1396-1401,共6页
World Chinese Journal of Digestology
基金
国家自然科学基金资助项目
No.81160065
江西省科技支撑基金资助项目
No.2009JX0096~~
关键词
骨髓间充质干细胞
高迁移蛋白B1
急性肝衰竭
Bone marrow stromal stem cells； High mobility group box B1 protein； Acute liver failure
