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骨髓间充质干细胞治疗慢加急性肝衰竭小鼠实验研究

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目的:研究骨髓间充质干细胞(hBMSCs)对慢加急性肝衰竭(ACLF)模型小鼠的治疗作用.方法:60只BALB/cJ小鼠随机分为正常组(n=8)和ACLF造模组(n=52),采用四氯化碳(CCl4)诱导法构建ACLF小鼠模型,ACLF造模组剔除死亡小鼠,随机分为模型组(n=11)、hBMSCs低剂量治疗组(n=12)、中剂量治疗组(n=12)、高剂量治疗组(n=12).采用生化分析仪检测小鼠血清谷氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、总蛋白(TP)和白蛋白(ALB)水平;超敏多因子发光法(MSD)检测血清白细胞介素(IL)-Iβ、IL-6、IL-10、肿瘤坏死因子-α(TNF-α)、趋化因子配体1(KC/GRO)水平含量;苏木素-伊红(HE)和Masson染色,评价肝组织病理损伤程度.结果:与正常组相比,模型组AST、ALT、TBIL、TP、ALB水平显著升高(F=5.409、26.27、21.20、23.44、22.81,均P<0.001),AST/ALT比值显著降低(F=3.036,P<0.05).与ACLF模型组比较,hBMSCs低、中剂量治疗组血清AST、ALT、TBIL水平显著降低(均P<0.05);中、高剂量治疗组AST/ALT比值显著升高(均P<0.05);hBMSCs低剂量治疗组血清IL-6、KC/GRO水平显著降低(均P<0.05);hBMSCs低、中剂量治疗组IL-1β、TNF-α水平降低(均P<0.05),而在hBMSCs低、中、高剂量治疗组中IL-10 均升高(均P<0.05);低、中、高剂量治疗组TP、ALB、IFN-γ、IL-2、IL-5 差异没有统计学意义(均P>0.05);hBMSCs低、中剂量治疗组肝组织炎细胞浸润及坏死区域均显著减少(均P<0.05),肝组织胶原纤维阳性面积显著降低(均P<0.05).结论:hBMSCs对CCl4 诱导的ACLF小鼠模型具有显著的治疗作用,治疗效果未见剂量依赖,其中低剂量组治疗效果更佳.
Experimental investigation of human bone marrow mesenchymal stem cells on acute-on-chronic liver failure in mice
Objective:To evaluate the therapeutic potential of human bone marrow mesenchymal stem cells(hBMSCs)on acute-on-chronic liver failure(ACLF)mice model.Methods:A total of 60 BALB/cJ mice were randomly divided into healthy control group(n=8)and ACLF model group(n=52).ACLF mice was established by intraperitoneal injection of carbon tetrachloride(CCl4).ACLF model group excluded dead mice were randomly divided into model group(n=11),hBMSCs low dose group(n=12),medium dose group(n=12)and high dose group(n=12).The levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),total bilirubin(TBIL),total protein(TP),albumin(ALB)in mice were detect by a biochemical analyzer.Serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α)and chemokine ligand 1(KC/GRO)were detected by MSD elec trochemiluminescence technology.HE and Masson staining were used to evaluate the degree of pathological damage in liver tissue.Results:Compared with the control group,the serum level of TBIL,AST,ALT,TP and ALB were significantly increased(F=5.409,26.27,21.20,23.44,22.81,all P<0.001),AST/ALT was significantly decreased(F=3.036,P<0.05).Compared with the ACLF model group,the serum level of TBIL,AST and ALT were significantly decreased in the low,and medium dose group(all P<0.05),AST/ALT was significantly increased both in medium and high dose group(all P<0.05).The serum levels of pro-inflammatory cytokines IL-6 and KC/GRO were significantly decreased in low dose group(all P<0.05).IL-1β and TNF-α were significantly decreased in low,and medi-um dose group(all P<0.05),while anti-inflammatory cytokines IL-10 was significantly increased in the treated groups(all P<0.05).TP,ALB,IFN-γ,IL-2 and IL-5 were not significantly changed in all the treated groups(all P>0.05).The infiltration and necrosis area of inflammatory cells in the low and medium groups were significantly decreased(both P<0.05),and the positive area of collagen fibers in liver tissue was significantly reduced(both P<0.05).Conclusion:hBMSCs has an obvious therapeutic effect on CCl4-induced ACLF mice model and the therapeutic effect is not dose-dependent.In contrast,low-dose group has better therapeutic effect.

human bone marrow mesenchymal stem cellsacute-on-chronic liver failurecytokineshepatic fibrosis

闻家兴、杨阳、孟玉静、董林毅

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天津医科大学药学院药物分析学系,天津 300070

天津中医药大学医学实验动物中心,天津 300381

天津凯诺医药科技有限公司,天津 300457

人骨髓间充质干细胞 慢加急性肝衰竭 炎性因子 肝纤维化

2025

天津医科大学学报
天津医科大学

天津医科大学学报

影响因子:0.881
ISSN:1006-8147
年,卷(期):2025.31(1)