中国组织工程研究2020，Vol.24Issue(13)：1996-2004,9.DOI:10.3969/j.issn.2095-4344.2048
人脂肪干细胞来源外泌体对四氯化碳诱导肝纤维化模型大鼠的治疗作用
Therapeutic effect of human adipose stem cells derived exosomes on carbon tetrachloride induced liver fibrosis in rats
摘要
Abstract
BACKGROUND: Liver fibrosis has higher morbidity and mortality. Activation and proliferation of hepatic stellate cells is a key link in the progression of liver fibrosis. At present, there are still no effective anti-fibrosis agents targeting single links or targets.OBJECTIVE: To analyze the effect of human adipose stem cells derived exosomes on rats with liver fibrosis induced by carbon tetrachloride. METHODS: Human adipose stem cells were obtained from healthy people by enzyme dissolution method. After in vitro culture, human adipose stem cells derived exosomes were obtained by multiple ultrafiltration. Different concentrations of exosomes were used to treat the hepatic stellate cells activated by transforming growth factor β1. The human adipose stem cells activated by transforming growth factor β1 were treated with different concentrations of exosomes. The expression of α-smooth actin in the cells was detected by quantitative PCR, and the growth and apoptosis of activated hepatic stellate cells were detected by CCK-8 and flow cytometry respectively. Rat models of liver fibrosis were established by intraperitoneal injection of carbon tetrachloride and treated by tail vein injection of exosomes. Rat liver function, serum levels of type III procollagen and type IV collagen, and Ishak score were determined. Semi-quantitative analysis of liver fibrosis was performed. The expression levels of tissue inhibitor of matrix metalloproteinase-1, matrix metalloproteinase 9 and α-smooth actin in liver tissue were measured by immunofluorescence method. The study protocol was approved by the Animal Ethics Committee and Medical Ethics Committee, Tongji University, China in January, 2017. RESULTS AND CONCLUSION: Human adipose stem cells derived exosomes inhibited the proliferation of activated hepatic stellate cells. The possible mechanism is to inhibit the proliferation of activated macrophages, reduce the production of collagen fibers, α-smooth actin actin, and tissue inhibitor of matrix metalloproteinase-1, and to increase the expression of matrix metalloproteinase 9. These findings suggest that exosomes can be used to treat carbon tetrachloride induced liver fibrosis.关键词
人脂肪干细胞/外泌体/细胞外分泌物质/肝纤维化/肝星状细胞/四氯化碳/转化生长因子β1/α-平滑肌蛋白/基质金属蛋白酶组织抑制物1/基质金属蛋白酶Key words
human adipose stem cells/exosomes/excessive extracellular matrix/liver fibrosis/hepatic stellate cells/carbon tetrachloride/transforming growth factor beta 1/α-smooth muscle actin/tissue inhibitor of metalloproteinase-1/matrix metalloproteinase 9分类
医药卫生引用本文复制引用
李洪超,吴君,金银鹏,傅青春,王皙,李莉,李震宇,臧祖盛,周桁,王晓今,陈成伟,程明亮..人脂肪干细胞来源外泌体对四氯化碳诱导肝纤维化模型大鼠的治疗作用[J].中国组织工程研究,2020,24(13):1996-2004,9.基金项目
Nanjing Military Region Medical Innovation Major Project, No. 14ZX01 (to FQC) （to FQC）
China Hepatitis南京军区医学创新重大课题(14ZX01),项目负责人:傅青春 （14ZX01）
中国肝炎防治基金-天 晴 肝 病 研 究 基 金 项 目(TQGB20150104),项目负责人:金银鹏 （TQGB20150104）
