| 薛方苏,钱 雷,陈国萍,朱述阳,马 苗.白介素-35对哮喘患者外周血单个核细胞糖皮质激素抵抗的作用及机制研究[J].,2020,(22):4257-4261 |
| 白介素-35对哮喘患者外周血单个核细胞糖皮质激素抵抗的作用及机制研究 |
| Effect and Mechanism Research of Interleukin-35 on Glucocorticoid Resistance of Peripheral Blood Mononuclear Cells in Patients with Asthma |
| 投稿时间：2020-06-08 修订日期：2020-06-30 |
| DOI：10.13241/j.cnki.pmb.2020.22.012 |
| 中文关键词: 白介素-35 哮喘 单个核细胞 糖皮质激素 |
| 英文关键词: Interleukin-35 Asthma Mononuclear cells Glucocorticoid |
| 基金项目:江苏省临床医学科技专项项目（BE2015611） |
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| 中文摘要: |
| 摘要 目的：探讨白介素（IL）-35对哮喘患者外周血单个核细胞糖皮质激素抵抗的作用及机制。方法：选择2017年8月至2018年11月于徐州医科大学附属医院和滨海县人民医院确诊的哮喘患者54例，其中20例为激素抵抗型患者（SR组），34例为激素敏感型患者（SS组）。采用Luminex200液相芯片法检测哮喘患者外周血IL-35的水平；体外分离培养两组患者外周血单个核细胞：通过检测细胞培养上清IL-6的水平确定地塞米松（DEX）对单个核细胞的半抑制浓度及最大抑制率；流式细胞术检测单个核细胞内磷酸化-P38丝裂原活化蛋白激酶（p-p38 MAPK）平均荧光强度及表达p-p38 MAPK单个核细胞率。结果：SR组患者外周血IL-35水平显著低于SS组（P<0.05）；与SS组比较，SR组DEX半抑制浓度显著升高而最大抑制率显著降低，且单个核细胞内p-p38 MAPK平均荧光强度显著升高（P<0.05）；哮喘患者外周血清IL-35水平与DEX半抑制浓度和外周血单个核细胞内p-p38 MAPK荧光强度呈负相关(r=-0.351, r=-0.352，P<0.001)，与最大抑制率呈正相关(r=0.450, P<0.001)；SS组：与IL-35+脂多糖（LPS）组比较，IL-35+DEX+LPS组表达p-p38 MAPK 单个核细胞率显著降低，差异有统计学意义（P<0.05）；SR组：IL-35+DEX+LPS组表达p-p38 MAPK 单个核细胞率无显著变化，差异无统计学意义（P>0.05）。结论：IL-35能够减轻哮喘患者糖皮质激素抵抗，其机制可能是通过抑制单个核细胞内p-p38 MAPK的表达。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the effect and mechanism of interleukin (IL) -35 on glucocorticoid resistance of peripheral blood mononuclear cells in patients with asthma. Methods: 54 asthma patients who were diagnosed in Affiliated Hospital of Xuzhou Medical University and Binhai People's Hospital from August 2017 to November 2018 were selected, including 20 patients with hormone resistant type (SR group), 34 patients with hormone sensitive type (SS group). The level of IL-35 in peripheral blood of asthmatic patients was detected by Luminex 200 liquid chip method. Peripheral blood mononuclear cells were isolated and cultured in vitro from two groups of patients: The semi inhibitory concentration and maximum inhibitory rate of dexamethasone (DEX) on mononuclear cells were determined by detecting the level of IL-6 in cell culture supernatant. The average fluorescence intensity of phosphorylated-p38 mitogen activated protein kinase (p-p38 MAPK) and the percentage of mononuclear cells expressing p-p38 MAPK were detected by flow cytometry. Results: The level of IL-35 in serum of SR group was significantly lower than that of the SS group (P<0.05). Compared with SS group, the optimal semi-inhibitory concentration of DEX was significantly increased while the maximum inhibitory rate was significantly decreased, and the average fluorescence intensity of p-p38 MAPK in mononuclear cells was significantly increased of SR group (P<0.05). The level of IL-35 in peripheral serum of asthma patients was negatively correlated with the semi inhibitory concentration of DEX and the fluorescence intensity of p-p38 MAPK in peripheral blood mononuclear cells (r=-0.351, r=-0.352, P<0.001), positively correlated with the maximal inhibition rate (r=0.450, P<0.001). SS group: compared with IL-35+lipopolysaccharide (LPS) group, the expression of p-p38 MAPK in IL-35 + DEX + LPS group was significantly decreased, the difference was statistically significant (P<0.05). SR group: There was no significant difference in the rate of mononuclear cells expressing p-p38 MAPK in the IL-35+DEX+LPS group (P>0.05). Conclusion: IL-35 can reduce glucocorticoid resistance in asthma patients, the mechanism may be through inhibiting the expression of p-p38 MAPK in mononuclear cells. |
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