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


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
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    摘要:

    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(1.0×107 cells/kg)、中剂量(5.0×106 cells/kg)、低剂量组(2.5×106 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1.0×107、5.0×106、2.5×106 cells/kg剂量下多次静脉注射大鼠安全性好,可下调IL-17A水平

    Abstract:

    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-α and 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 1×107, 5.0×106, 2.5×106 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 1×107、5.0×106、2.5×106 cells/kg, and can reduce the level of IL-17A

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  • 在线发布日期: 2023-07-26
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