论文部分内容阅读
脓毒症是近年来的医学难题之一,迫切需要探讨新的治疗手段.以往研究发现,骨髓间充质干细胞具有免疫调节作用,免疫细胞因子白介素 10(IL-10)是细胞因子分泌的抑制因子,具有很好的抗炎作用.因此构建了携带小鼠 IL-10(mIL-10)的腺病毒载体,用它来感染骨髓间充质干细胞(BMSC),并通过载体上的绿色荧光蛋白来筛选过表达 mIL-10 基因的骨髓间充质干细胞(BMSC-mIL-10).随后,运用盲肠结扎穿孔法在小鼠体内建立脓毒症模型,并观察 BMSC-mIL-10 在脓毒症中的治疗作用.研究发现,和单纯 BMSC 治疗组相比,BMSC-mIL-10 可以明显降低脓毒症老鼠体内炎症因子的产生,这包括TNF-α、IL-6、IL-1α和 IL-1β等,同时,BMSC-mIL-10 治疗组小鼠的肺部和肾脏炎症反应减轻,体重丢失下降,死亡率明显降低.为进一步探讨 BMSC-mIL-10 治疗机制,运用 Western blot 和免疫荧光染色方法发现 BMSC-mIL-10 组上清液可以抑制巨噬细胞和中性粒细胞中 LPS 引起的 NF-κB的激活.上述结果表明,骨髓间充质干细胞过表达 IL-10 有望成为脓毒症治疗的潜在手段之一.
Sepsis is one of the medical problems in recent years, and there is an urgent need to explore new therapeutic approaches. Previous studies found that bone marrow mesenchymal stem cells have immunomodulatory effects. The immune cytokine interleukin 10 (IL-10) is an inhibitor of cytokine secretion Factor, and has a good anti-inflammatory effect.Therefore, an adenovirus vector carrying mouse IL-10 (mIL-10) was constructed, which was used to infect BMSCs and transfected by the green fluorescent protein (BMSC-mIL-10) overexpressing mIL-10 gene.Secondly, sepsis model was established in mice by cecal ligation and perforation method, and the effect of BMSC-mIL-10 on sepsis BMSC-mIL-10 significantly reduced the production of inflammatory cytokines in septic mice, including TNF-α, IL-6, IL-1α and IL- At the same time, the inflammatory reaction of lung and kidney of mice in BMSC-mIL-10 treatment group were alleviated, the weight loss was decreased and the mortality rate was significantly reduced.In order to explore the mechanism of BMSC-mIL-10 treatment, Western blot and immunofluorescence staining The method was found to inhibit BMSC-mIL-10 group supernatant LPS-induced activation of NF-κB in macrophages and neutrophils.The above results suggest that the over-expression of IL-10 by bone marrow mesenchymal stem cells is expected to be one of the potential treatments for sepsis.