间充质干细胞干预对糖尿病脓毒症大鼠的肺损伤及肺脏炎症微环境作用的研究

MSC intervention on lung injury of diabetic rats with sepsis and its interaction with lung inflammation

目的探讨间充质干细胞(MSC)对糖尿病大鼠脓毒症模型的肺组织结构及细胞因子表达水平的影响。方法高糖高脂饮食喂养联合链脲佐菌素(STZ),结合盲肠结扎穿孔术(CLP)制备大鼠糖尿病脓毒症模型,随机分为对照组、假手术组、脓毒症组和MSC治疗组。分别在术后6、12、18、24 h观察肺组织病理改变,肺组织匀浆测SP-D、TNF-α、IFN-γ、IL-10表达水平。结果 CLP术后肺组织SP-D、TNF-α和IFN-γ表达水平随着时间发展逐渐增加,IL-10表达水平则呈现"升高-下降-再升高-再下降"的趋势。MSC干预增加非糖尿病脓毒症大鼠肺组织SP-D、TNF-α与IL-10表达水平,减少IFN-γ表达水平;MSC干预减少糖尿病脓毒症大鼠肺组织SP-D与TNF-α表达水平,对IFN-γ表达水平无影响,对IL-10表达水平起到先增后减的作用。结论建立糖尿病大鼠脓毒症模型可观测到间充质干细胞对脓毒症的炎症与器官损伤有影响,但其具体作用取决于机体免疫状态及间充质干细胞干预时机的选择。

Objective To investigate the effects of mesenchymal stem cells （MSCs） on the pathological structure and cytokine expression of lung tissue in septic model of diabetic rats. Methods Diabetic rats were randomly divided into control, sham-operation, sepsis and MSC-treated groups. The diabetic model was induced by high-sucrose and high-fat diet combined with streptozotocin and cecal ligation and puncture. The pathological changes of lung tissue were observed at 6, 12, 18 and 24 hours after operation respectively, and the expression of SP-D, TNF-α, IFN-γ and IL-10 in lungs were measured. Results The levels of SP-D, TNF-α and IFN-γ in lung tissue increased gradually with the elongation of time after CLP. The expression of IL- 10 in lung tissue increased and then decreased. The trend of MSC intervention increased the content of SP-D, TNF-α and IL-10 in the lung tissue of non-diabetic septic rat model and reduced the content of IFN-γ. MSC intervention reduced the SP-D and TNF-α content. The intervention of MSC had no effect on the content of IFN-γ in the lung tissue of diabetic septic rats. However, it increased and then decreased the content of IL-10. Conclusions The model of sepsis in diabetic rats can be established by feeding combined high-sugar and high-fat diet and streptozotocin combined with cecal ligation and puncture. Mesenchymal stem cells affect sepsis inflammation and organ damage. But its specific role depends on the immune status and the timing of mesenchymal stem cell selection.