摘要
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)大鼠的炎症抑制作用及机制。方法SD大鼠随机分为对照组、模型组、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BMSC,取第4代细胞用于实验,BMSC组大鼠尾静脉注射1×10^(6)个BMSC,对照组和模型组大鼠尾静脉注射等量生理盐水。造模后72 h,血气分析仪检测血氧分压(PaO_(2))、动脉血二氧化碳分压(PaCO_(2));ELISA检测大鼠血清总胆红素(TB)、白蛋白(ALB)、血肌酐(Scr)、尿素氮(BUN)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、环磷酸腺苷(cAMP)的含量;HE染色观察肺、肝和肾组织病变情况;Western blot法检测大鼠肺、肝和肾组织中蛋白激酶A(PKA)、核因子κB p65(NF-κB p65)蛋白表达。结果与对照组相比,模型组和BMSC组PaO_(2)显著降低,PaCO_(2)显著增高;TB、Cr、BUN、TNF-α和IL-6水平升高,ALB和cAMP水平降低,肺、肝、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_(2)显著升高,PaCO显著降低,TB、Cr、BUN、TNF-α、IL-6水平降低,ALB和cAMP水平升高,肺、肝、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BMSC可减轻MODS大鼠器官功能损害,抑制炎症因子释放,与cAMP/PKA/NF-κB信号通路的表达水平改变有关。
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^(6) 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_(2))and arterial carbon dioxide partial pressure(PaCO_(2))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_(2)in model group and BMSC group significantly decreased,while the PaCO_(2)significantly increased.TB,Cr,BUN,TNF-αand 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_(2)in BMSC group increased significantly,while its PaCO_(2)decreased markedly.It’s also detected decreased TB,Cr,BUN,TNF-αandIL-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.
作者
尹燕涛
曹秋梅
马炳辰
YIN Yantao;CAO Qiumei;MA Bingchen(Emergency department of Beijing Tongren Hospital Affiliated to Capital Medical University,Beijing 100176,China)
出处
《细胞与分子免疫学杂志》
CAS
CSCD
北大核心
2022年第8期673-678,共6页
Chinese Journal of Cellular and Molecular Immunology
基金
国家自然科学基金(81860238)。
