人脐带间充质干细胞连续静脉注射对大鼠的安全性及肝脏的影响  

Study on the safety of continuous intravenous injection of human umbilical cord mesenchymal stem cells in rats and its effect on hepatic IL-17 signaling pathway

作　　者：梅小利[1] 杜伟[1] 吴思澜 杨雪[1,2] 于冰 李聪 黄崇刚 MEI Xiaoli;DU Wei;WU Silan;YANG Xue;YU Bing;LI Cong;HUANG Chonggang(Chongqing Academy of Chinese Materia Medica,Chongqing Drug Safety Evaluation Center,Chongqing 400065,China;Chongqing College of Traditional Chinese Medicine,Chongqing 402760,China;Shandong Institute of Pharmaceutical Research,Jinan 250062,China;Shandong First Medical University,Shandong Academy of Medical Sciences,Jinan 250062,China;Institute of Medical,Chinese Academy of Medical Sciences,Kunming 650031,China)

机构地区：[1]重庆市中药研究院·重庆市药物安全评价中心,重庆400065 [2]重庆中医药学院,重庆402760 [3]山东省药物研究院,山东济南250062 [4]山东第一医科大学·山东省医学科学院,山东济南250062 [5]中国医学科学院医学生物学研究所,云南昆明650031

出　　处：《西部医学》2023年第7期959-963,共5页Medical Journal of West China

基　　金：重庆市技术创新与应用发展专项重点项目(cstc2020jscx-lyggX0004)。

摘　　要：目的 探讨人脐带间充质干细胞(hUC-MSCs)多次注射对大鼠的安全性及肝脏的影响,为hUC-MSCs临床应用的安全性提供支持。方法 取SPF级健康SD大鼠50只,随机分成阴性对照组(生理盐水)、溶媒对照组(白蛋白)、hUC-MSCs高剂量(1.0×10^(7)cells/kg)、中剂量(5.0×10^(6)cells/kg)、低剂量组(2.5×10^(6) cells/kg),每组10只,尾静脉注射给药4次,1次/周。在末次给药后24 h,采集大鼠血样,检测血生化指标(TBIL、AST、ALT、GGT)、血清细胞因子(IFN-γ、IL-17、TNF-α)以及T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD8^(+));观察大鼠肝脏重量、脏体比指数及组织病理学变化;提取大鼠肝脏组织总RNA,qRT-PCR分析Act1、IL-17A、Hsp90aa1基因水平的表达情况。结果 hUC-MSCs高、中、低剂量组多次静脉注射后,大鼠血生化、血清细胞因子IFN-γ、IL-17、TNF-α以及T淋巴细胞亚群、肝脏重量、脏体指数及组织病理学变化与阴性对照组、溶媒对照组相比差异无统计学意义(P>0.05)。hUC-MSCs可明显降低肝组织中IL-17A mRNA表达水平,对Act1、Hsp90aa1 mRNA表达未见明显影响(P>0.05)。结论 hUC-MSCs在1.0×10^(7)、5.0×10^(6)、2.5×10^(6) cells/kg剂量下多次静脉注射大鼠安全性好,可下调IL-17A水平。Objective To observe the safety of human umbilical cord mesenchymal stem cells(hUC-MSCs)injected into rats for many times and its effect on rat's liver,so as to provide support for the safety hUC-MSCs in clinical application.Methods Fifty SPF healthy SD rats were randomly divided into negative control group,vehicle control group,high dose,medium dose and low dose groups of hUC-MSCs,with ten rats in each group.The drugs were injected into the caudal vein 4 times,once a week.At 24 hours after the last administration,blood samples were collected for the detection of blood biochemistry,serum cytokine IFN-γ、IL-17、TNF-αand T lymphocyte subsets.The liver weight,organ body ratio index and histopathological changes were observed.Total RNA was extracted from rat liver tissue,and the expression of Act1,IL-17A and Hsp90aa1 genes was analyzed by qRT-PCR.Results After multiple intravenous injections of 1×10^(7),5.0×10^(6),2.5×10^(6) cells/kg hUC-MSCs,there were no significant differences in blood biochemistry,serum cytokines IFN-γ,IL-17,TNF-α,T lymphocyte subsets,liver weight,organ body index and histopathological changes between negative control group and solvent control group(P>0.05).hUC-MSCs could significantly reduce the expression of IL-17A mRNA in liver tissue,but had no significant effect on the expression of Act1 and hsp90aa1 mRNA.Conclusion hUC-MSCs are safe to be injected intravenously at doses of 1×10^(7)、5.0×10^(6)、2.5×10^(6) cells/kg,and can reduce the level of IL-17A.

关 键 词：人脐带间充质干细胞 安全性 IL-17信号通路 大鼠 

分 类 号：R394.2[医药卫生—医学遗传学]