人脐带间充质干细胞经不同移植途径治疗肝硬化大鼠模型的效果比较  被引量:1

Efficacy of human umbilical cord mesenchymal stem cells via different transplantation approaches in treatment of rats with liver cirrhosis

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作  者:邱英麒 王宏伟 朱宏岩 於洪亮 谢凡 姜翠宝 QIU Yingqi;WANG Hongwei;ZHU Hongyan;YU Hongliang;XIE Fan;JIANG Cuibao(Clinical Research Center of Haikou People’s Hospital,Haikou 570208,China;Shanghai Quansheng Bioengineering Co.,Ltd.,Shanghai 201401,China)

机构地区:[1]海口市人民医院临床研究中心,海口570208 [2]上海泉生生物工程有限公司,上海201401

出  处:《临床肝胆病杂志》2023年第12期2851-2857,共7页Journal of Clinical Hepatology

基  金:国家卫健委干细胞临床研究项目(MR-46-21-014648)。

摘  要:目的探讨人脐带间充质干细胞(hUC-MSC)制剂(冷冻细胞制剂和新鲜细胞制剂)通过两种给药途径(门静脉/尾静脉)移植对肝硬化模型大鼠的治疗效果。方法70只SPF级健康雄性SD大鼠随机分为正常组(n=13,予以普通自来水及普通鼠粮喂养)和肝硬化模型组(n=57,给予CCl4/橄榄油溶液混合液,皮下多点注射造模)。第8周观察两组大鼠的生长状况,取正常组及肝硬化模型组小鼠各3只行组织病理学检查,明确肝硬化形成。选取50只肝硬化模型组大鼠按随机数字表法分为模型组、门静脉(新鲜细胞制剂)组、门静脉(冷冻细胞制剂)组、尾静脉(新鲜细胞制剂)组、尾静脉(冷冻细胞制剂)组,每组10只。分别取新鲜或冷冻hUC-MSC制剂通过门静脉或尾静脉途径移植。给药4周后,比较各组大鼠肝功能指标、肝纤维化程度变化。计量资料两组间比较采用成组t检验;多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果造模第8周时,肝硬化模型组大鼠肝脏形成多个大小不等的假小叶,符合肝硬化诊断标准,ALT、AST、TBil、ALP水平相较于正常组均明显升高(P值均<0.001),肝硬化大鼠造模成功。第12周时5组大鼠ALT、AST、TBil、ALP水平比较差异均有统计学意义(F值分别为232.00、177.10、112.30、121.70,P值均<0.001)。进一步两两比较结果显示,模型组ALT、AST、TBil、ALP水平均显著高于正常组(P值均<0.01);门静脉(新鲜细胞制剂)组、门静脉(冷冻细胞制剂)组、尾静脉(新鲜细胞制剂)组、尾静脉(冷冻细胞制剂)组ALT、AST、TBil、ALP水平均显著低于模型组(P值均<0.01)。结论hUC-MSC移植4周可改善肝硬化模型大鼠肝功能和肝纤维化程度,细胞制剂的不同、给药途径的不同对治疗结果无明显影响。Objective To investigate the therapeutic effect of the frozen and fresh preparations of human umbilical cord mesenchymal stem cells(hUC-MSC)on a rat model of liver cirrhosis after transplantation via the portal vein or the caudal vein.Methods A total of 70 specific pathogen-free healthy male Sprague-Dawley rats were randomly divided into normal group(13 rats fed with ordinary tap water and rat food)and liver cirrhosis model group(57 rats given subcutaneous multipoint injection of mixed carbon tetrachloride/olive oil solution).At week 8,the growth of rats was observed for both groups,and 3 rats were selected from each group for histopathological examination to confirm the formation of liver cirrhosis.A total of 50 rats were selected from the liver cirrhosis model and were divided into model group,portal vein group+fresh cell preparation group,portal vein+frozen cell preparation group,caudal vein+fresh cell preparation group,and caudal vein+frozen cell preparation group using a random number table,with 10 rats in each group.Fresh or frozen hUC-MSC were transplanted via the portal vein or the caudal vein,and after 4 weeks of administration,the different groups were compared in terms of the changes in liver function parameters and liver fibrosis degree.Continuous data were expressed as mean±standard deviation,and the independent-samples t test was used for comparison between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results At week 8 of modeling,the model group showed the formation of pseudolobules of different sizes in the liver and met the diagnostic criteria for liver cirrhosis,with significant increases in the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),and alkaline phosphatase(ALP)compared with the normal group(all P<0.001),suggesting that the rat model of liver cirrhosis was established successfully.There were significan

关 键 词:肝硬化 实验性 间质干细胞移植 大鼠 SPRAGUE-DAWLEY 

分 类 号:R575.2[医药卫生—消化系统] R-332[医药卫生—内科学]

 

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