大蒜素对慢性阻塞性肺疾病小鼠免疫失衡的调控作用

Regulatory effect of allicin on immune imbalance in mice with chronic obstructive pulmonary disease

目的探讨大蒜素通过影响Notch信号调节慢性阻塞性肺疾病小鼠免疫失衡的机制。方法利用被动吸烟和脂多糖法诱导建立慢性阻塞性肺疾病小鼠模型。慢性阻塞性肺疾病模型BALB/c小鼠分成模型组(生理盐水处理)、实验低、中、高剂量组(10、20和30 mg·kg^(-1)的大蒜素治疗)、实验高剂量+Jagged1组(40 mg·kg^(-1)大蒜素和1 mg·kg^(-1)Jagged1治疗);对照组为正常BALB/c小鼠(生理盐水处理)。以蛋白质印迹法检测Notch1、Hes1蛋白表达;检测小鼠最大呼气流量(PEF)、每分钟通气量(MV),吸气峰流量(PIF);以流式细胞仪检测CD4^(+)/CD8^(+);以酶联免疫吸附(ELISA)法检测白细胞介素-1β(IL-1β),计数肺泡灌洗液中炎性细胞的数目。结果对照组、模型组、实验高剂量组、实验高剂量+Jagged1组Notch1蛋白表达水平为0.20±0.02、0.44±0.03、0.23±0.02、0.36±0.04,Hes1蛋白表达水平为0.30±0.03、0.57±0.04、0.31±0.02、0.45±0.02,PEF为(3.18±0.15)、(1.68±0.12)、(3.15±0.18)和(2.25±0.23)mL·s^(-1),MV为(42.03±3.66)、(26.00±1.53)、(39.77±2.10)和(29.84±2.30)mL·s^(-1),CD4^(+)/CD8^(+)水平为3.02±0.33、1.06±0.13、2.61±0.17、1.74±0.22,IL-1β为(17.39±1.25)、(39.90±3.26)、(18.72±1.58)和(29.46±2.13)pg·mL^(-1),炎性细胞总数为(40.82±2.53)×10^(4)、(86.83±5.66)×10^(4)、(43.91±1.67)×10^(4)和(59.84±6.49)×10^(4)cell·mL^(-1),以上指标,模型组与对照组相比较,差异均有统计学意义(均P<0.05);实验高剂量组与模型组相比较,差异均有统计学意义(均P<0.05);实验高剂量+Jagged1组与实验高剂量组比较,差异均有统计学意义(均P<0.05)。结论大蒜素通过抑制Notch信号改善慢性阻塞性肺疾病小鼠免疫失衡。

Objective To investigate the mechanism of allicin regulating immune imbalance in mice with chronic obstructive pulmonary disease by affecting Notch signaling.Methods A mouse model of chronic obstructive pulmonary disease was induced by passive smoking and lipopolysaccharide.Chronic obstructive pulmonary disease model BALB/c mice were divided into model group(normal saline treatment),experimental-L,-M and-H groups(10,20 and 30 mg·kg^(-1)allicin treatment),experimental-H+Jagged1 group(40 mg·kg^(-1)allicin and1 mg·kg^(-1)Jagged1 treatment).The control group was normal BALB/c mice(normal saline treatment).The expression of Notch1 and Hes1protein was detected by Western blotting.The peak expiratory flow(PEF),minute ventilation(MV)and peak inspiratory flow(PIF)were measured.CD4^(+)/CD8^(+)was detected by flow cytometry;interleukin-1β(IL-1β)was detected by enzyme-linked immunosorbent assay(ELISA),and the number of inflammatory cells in alveolar lavage fluid was counted.Results The expression levels of Notch1 protein in the control group,model group,experimental-H group,and experimental-H+Jagged1 group were 0.20±0.02,0.44±0.03,0.23±0.02,0.36±0.04;Hes1 protein expression were 0.30±0.03,0.57±0.04,0.31±0.02,0.45±0.02;PEF were(3.18±0.15),(1.68±0.12),(3.15±0.18)and(2.25±0.23)m L·s^(-1);MV were(42.03±3.66),(26.00±1.53),(39.77±2.10)and(29.84±2.30)mL·s^(-1);CD4^(+)/CD8^(+)levels were 3.02±0.33,1.06±0.13,2.61±0.17 and 1.74±0.22;IL-1βwere(17.39±1.25),(39.90±3.26),(18.72±1.58)and(29.46±2.13)pg·m L^(-1);the total number of inflammatory cells were(40.82±2.53)×10^(4),(86.83±5.66)×10^(4),(43.91±1.67)×10^(4)and(59.84±6.49)×10^(4)cell·m L^(-1),the above indicators,control group compared with the model group,the differences were statistically significant(P<0.05);compared with the experimental-H group and the model group,the differences were statistically significant(P<0.05);the experimental-H+Jagged1 compared with the experimental-H group,the differences were statistically significant(P<0.05).Conclusion Allicin improves the immune imbalance in mice with chronic obstructive pulmonary disease by inhibiting Notch signaling.