Yin Yantao, Cao Qiumei, Ma Bingchen
Emergency department of Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing 100176, China. *Corresponding author, E-mail:
Emergency department of Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing 100176, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2022 Aug;38(8):673-678.
Objective To observe the anti-inflammatory effect and mechanism of bone marrow mesenchymal stem cell (BMSC) on multiple organ dysfunction syndrome (MODS) rats. Methods SD rats were randomly divided into control group, model group and BMSC group, with 10 rats in each group. Rats in model group and BMSC group were intraperitoneally injected with 7 mg/kg lipopolysaccharide (LPS) to establish MODS models. Rat BMSCs were cultured in vitro, and the fourth generation cells were used for experiments. The rats in BMSC group were injected with 1×10 BMSCs through the tail vein, and the rats in control group and model group were injected with the same amount of normal saline through the tail vein. 72 hours after MODS model was established, blood oxygen partial pressure (PaO) and arterial carbon dioxide partial pressure (PaCO) were detected by blood gas analyzer. ELISA were used to detect the bilirubin (TB), albumin (ALB), serum creatinine (Scr), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and cyclic adenosine monophosphate (cAMP). HE staining was performed to observe pathological changes in lung, liver and kidney tissues. Western blot analysis was used to detect the protein expression of protein kinase A (PKA) and nuclear factor kappa-B p65 (NF-κB p65) in tissues of lung, liver and kidney. Results Compared with control group, PaO in model group and BMSC group significantly decreased, while the PaCO significantly increased. TB, Cr, BUN, TNF-α and IL-6 levels was found increased, and ALB and cAMP levels was found decreased, along with the decreased PKA protein expression levels in lung, liver and kidney tissues, and increased NF-κB p65 protein expression levels. Compared with model group, PaO in BMSC group increased significantly, while its PaCO decreased markedly. It's also detected decreased TB, Cr, BUN, TNF-α and IL-6 levels, increased ALB and cAMP levels, as well as increased PKA protein expression levels in lung, liver and kidney tissues, and decreased NF-κB p65 protein expression levels. Conclusion BMSCs can reduce the damaged organ function and inhibit the release of inflammatory factors in MODS rats. The mechanism may be related to the change of cAMP/PKA/NF-κB signaling pathway.
目的 观察骨髓间充质干细胞（BMSC）对多器官功能障碍综合征（MODS）大鼠的抗炎作用及机制。方法 将SD大鼠随机分为对照组、模型组和BMSC组，每组10只。模型组和BMSC组大鼠腹腔注射7 mg/kg脂多糖（LPS）建立MODS模型。体外培养大鼠BMSCs，取第4代细胞进行实验。BMSC组大鼠经尾静脉注射1×10个BMSCs，对照组和模型组大鼠经尾静脉注射等量生理盐水。建立MODS模型72小时后，用血气分析仪检测血氧分压（PaO）和动脉血二氧化碳分压（PaCO）。采用酶联免疫吸附测定法（ELISA）检测胆红素（TB）、白蛋白（ALB）、血清肌酐（Scr）、血尿素氮（BUN）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和环磷酸腺苷（cAMP）。进行苏木精-伊红（HE）染色观察肺、肝和肾组织的病理变化。采用蛋白质免疫印迹法（Western blot）分析肺、肝和肾组织中蛋白激酶A（PKA）和核因子κB p65（NF-κB p65）的蛋白表达。结果 与对照组比较，模型组和BMSC组PaO显著降低，PaCO显著升高。TB、Cr、BUN、TNF-α和IL-6水平升高，ALB和cAMP水平降低，肺、肝和肾组织中PKA蛋白表达水平降低，NF-κB p65蛋白表达水平升高。与模型组比较，BMSC组PaO显著升高，PaCO明显降低。TB、Cr、BUN、TNF-α和IL-6水平降低，ALB和cAMP水平升高，肺、肝和肾组织中PKA蛋白表达水平升高，NF-κB p65蛋白表达水平降低。结论 BMSCs可减轻MODS大鼠受损器官功能，抑制炎症因子释放。其机制可能与cAMP/PKA/NF-κB信号通路的改变有关。
