骨髓间充质干细胞对脓毒症小鼠急性肺损伤的影响

Effect of marrow derived mesenchymal stem cells on the treatment for acute pulmonary injury in sepsis mice

目的探讨骨髓间充质干细胞（BMSCs）对脓毒症小鼠急性肺损伤（AU）的治疗作用及机制。方法采用盲肠结扎穿孔术（CLP）复制小鼠脓毒症Au模型，125只Balb／c小鼠随机分为五组（每组25只）：假手术组（C组）、三个不同剂量BMSCs治疗组（L、M和H组）及脓毒症组（CLP组）。其中15只小鼠用于观察存活率，剩余10只用于观察其他指标。取第三代BMSCs，在制模成功5min后经小鼠尾静脉注射人小鼠体内，L、M和H组分别注入BMSCs1×10^4个、1×10^5个和1×10^6个，c组及CLP组注射等量生理盐水。在给予BMSCs后24h留取标本，检测肺组织形态学、肺组织湿干质量比（W／D）、动脉血氧分压（PaO：）和二氧化碳分压（PaCO2），血乳酸、血清TNF-α、IL-10及可溶性E选择素水平。结果与CLP组比较，H组24h及48h存活率提高，24h肺微血管充血、出血及炎症细胞浸润减少，病理评分、W／D值、PaCO2、血乳酸、TNF-α、可溶性E选择素水平降低，PaO2及IL-10水平增加，差异均有统计学意义（P〈0．05）。结论BMSCs可抑制Balb／c小鼠Au时血清TNF-α、可溶性E选择素水平，上调IL-10水平，减轻肺损伤严重程度，且该保护作用与BMSCs的剂量有关。

Objective To explore the possible mechanism and protective effect of marrow derived mesenchymal stem cells （BMSCs） on sepsis mice with acute lung injury （ALI）. Methods Sepsis mice with ALI were induced by cecal ligation and puncture （CLP）. One hundred and twenty - five Balb/c mice were randomly divided into five groups, twenty -five mice for every group. Sham control group （C group）, BMSCs treatment groups （L, M, H group） and ALI group （CLP group）. Five minutes after CLP, the mice in BMSCs treatment groups were intravenous administrated BMSCs though caudal vein of the mice （ 1 × 10^4 for L group, 1 × 10^5 for M group, 1 × 10^6 for H group）, the other two groups were given normal saline of the same quantity. Fifteen mice in each group were used to observe the survival status and the others were used to collect samples for assessment of histology, lung wet to dry ratio （W/D） arterial partial pressure of oxygen and carbon dioxide （PaO2 and PaCO2 ）, lactic acid, level of serum TNF - α, IL - 10 and soluble E selectin. Results Compared with CLP group, the survival rate in H group at 24 h and 48 h were significantly improved. What＇s more, there was a significant decrease in W/D, lung injury score, PaCO2, level of lactic acid, serum TNF - α and souble E selectin, a significant increase in PaO2 and level of serum IL - 10, in H group mice compared with CLP group mice at 24 h. Conclusion Treatment with BMSCs significantly reduces CLP - induced acute lung injury in Balb/c mice by inhibiting serum level of TNF - α, souble E selectin and increasing level of serum IL - 10, and the effect is related to its dose.