转化生长因子β1对脓毒症大鼠模型免疫功能的影响

Effect of Transforming Growth Factor β1 on Immunologic Function in Rat Model of Sepsis

目的观察转化生长因子β1 (TGF-β1)对脓毒症大鼠免疫抑制功能的作用。方法采用盲肠结扎穿孔术(CLP)制作大鼠脓毒症模型,经尾静脉注射给予20 ng/mL TGF-β1。ELISA法检测大鼠血清中炎性细胞因子肿瘤坏死因子α(TNF-α)和白细胞介素6 (IL-6)和抗炎细胞因子IL-4、IL-10的含量,Western blotting检测免疫器官中核转录因子E2相关因子2 (Nrf2)的蛋白表达,体外细胞实验检测TGF-β1对脂多糖(LPS)诱导的人外周血单核细胞系THP-1增殖、凋亡的影响。结果 CLP大鼠给予TGF-β1处理后血清中炎性细胞因子TNF-α和IL-6水平升高,抗炎细胞因子IL-4、IL-10水平下降(P <0.05);TGF-β1还可使CLP大鼠的脾、肝脏中Nrf2蛋白表达抑制;TGF-β1可抑制LPS诱导的THP-1增殖,促进凋亡(P <0.05)。结论 TGF-β1参与脓毒症大鼠的免疫抑制,可抑制免疫器官中Nrf2表达、抑制单核细胞增殖和促进凋亡。

Objective To explore the effect of transforming growth factorβ1(TGF-β1)on immunologic function in rat model of sepsis.Methods The rat model of sepsis was established by cecal ligation and puncture(CLP)after intravenous injection of 20 ng/mL TGF-β1.ELISA was used to detect the serum contents of inflammatory cytokines including tumor necrosis factorα(TNF-α)and interleukin(IL)-6 and anti-inflammatory cytokines including IL-4 and IL-10.Western blotting was used to detect the protein expression of nuclear factor E2 related factor 2(Nrf2)in the immune system organs.The effects of TGF-β1 on proliferation and apoptosis of human acute monocytic leukemia cell line THP-1 were determined in vitro.Results In CLP rats,the levels of inflammatory cytokines TNF-αand IL-6 in serum increased,and those of anti-inflammatory factors IL-4 and IL-10 decreased(P<0.05).TGF-β1 also inhibited the expression of Nrf2 in the spleen and liver of CLP rats.Moreover,TGF-β1 treatment in THP-1 cell line decreased proliferation and enhanced apoptosis compared with controls.Conclusion TGF-β1 is involved in the immunosuppression in sepsis rats,inhibiting the expression of Nrf2 in the immune system organs and inhibiting proliferation and promoting apoptosis of monocytes.