目的 探讨青蒿琥酯对卵清蛋白诱导的哮喘幼鼠气道重塑的影响及作用机制.方法 将SD幼鼠随机分为正常组、模型组(卵清蛋白激发)、阳性对照组(在模型组基础上给予0.2 mg·kg-1的地塞米松)、低剂量组(在模型组基础上给予10 mg·kg-1的青蒿琥酯)、高剂量组(在模型组基础上给予20 mg·kg-1的青蒿琥酯)、激动剂组(在模型组基础上给予20 mg·kg-1的青蒿琥酯和100 mg·kg-1的尼日利亚菌素钠盐),每组10只.处理结束后检测幼鼠气道重塑相关指标,使用蛋白质印迹法和实时荧光定量聚合酶链反应法检测NOD样受体蛋白3炎症小体(NLRP3)通路相关蛋白和mRNA表达水平,用酶联免疫吸附测定法检测炎性因子表达水平,用瑞氏-吉姆萨染色法检测肺泡灌洗液中炎性细胞分类和计数.结果 正常组、模型组、阳性对照组、高剂量组和激动剂组的NLRP3 mRNA 表达水平分别为 1.00±0.10、2.36±0.26、1.08±0.11、1.33±0.12和2.14±0.26,胱天蛋白酶1(caspase-1)mRNA表达量分别为1.00±0.13、1.92±0.22、1.22±0.12、1.44±0.10 和 1.82±0.14,白细胞介素-17(IL-17)分别为(22.41±1.15)、(56.74±6.54)、(28.72±2.75)、(32.69±3.73)和(58.40±4.46)pg·mL-1,中性粒细胞数分别为(4.04±0.32)×106、(12.70±1.05)× 106、(4.53±0.30)× 106、(4.67±0.18)×106 和(10.19±0.58)x106cell·mL-1.上述指标,模型组与正常组相比,阳性对照组、高剂量组与模型组相比,激动剂组与高剂量组相比,在统计学上差异均有统计学意义(均P＜0.05).结论 青蒿琥酯可显著改善卵清蛋白诱导的哮喘幼鼠的气道重塑,这可能是通过抑制NLRP3/caspase-1/白细胞介素1β(IL-1β)炎性通路实现的.
Objective To investigate the effect of artesunate on airway remodeling induced by ovalbumin in asthmatic young rats and its mechanism.Methods SD rats were randomly divided into normal group,model group(ovalbumin activation),positive control group(on the basis of model group,injected with 0.2 mg·kg-1 dexamethasone),low-dose group(on the basis of model group,injected with 10 mg·kg-1 artesunate),high-dose group(on the basis of model group,injected with 20 mg·kg-1 artesunate)and agonist group(on the basis of model group,injected with 20 mg·kg-1 artesunate and 100 mg·kg-1 nigerin sodium salt),with 10 rats in each group.Airway remodeling related indexes were detected after treatment.Western blot and real-time fluorescence quantitative polymerase chain reaction were used to detect Nod-like receptor protein 3(NLRP3)pathway-related protein and mRNA expression;enzyme-linked immunosorbent assay were used to detect inflammatory factors expression level,and the classification and count of inflammatory cells in alveolar lavage fluid were detected by Wright's-Giemsa Staining.Results The mRNA expression levels of NLRP3 in normal group,model group,positive control group,high-dose group and agonist group were 1.00±0.10,2.36±0.26,1.08±0.11,1.33±0.12,2.14±0.26,respectively;cysteine aspartate proteinase 1(caspase-1)mRNA expression levels were 1.00±0.13,1.92±0.22,1.22±0.12,1.44±0.10,1.82±0.14,respectively;interleukin-17(IL-17)inflammatory factor expression quantity were(22.41±1.15),(56.74±6.54),(28.72±2.75),(32.69±3.73),(58.40±4.46)pg·mL-1;neutrophil count were(4.04±0.32)×106,(12.70±1.05)×106,(4.53±0.30)×106,(4.67±0.18)× 106,(10.19±0.58)× 106 cell·mL-1.Compared the model group with the normal group,the positive group,the high dose group compared with the model group,the agonist group compared with the high dose group,the differences of the above indicators were statistically significant(all P＜0.05).Conclusion Artesunate can significantly improve airway remodeling in ovalbumin induced asthmatic pups,which may be achieved by inhibiting the NLRP3/caspase-1/interleukin 1 β(IL-1β)inflammatory pathway.
王丽艳;鲍星星;边俊梅
武汉市第三医院儿科,湖北武汉 430074
中医学
青蒿琥酯;哮喘;幼鼠;气道重塑;NOD样受体蛋白3炎症小体/半胱氨酸天冬氨酸蛋白酶1/白细胞介素-1β通路
artesunate;asthma;young mice;airway remodeling;Nod-like receptor protein 3 inflammasome/cysteine aspartic proteinase-1/interleukin-1 β pathway
《中国临床药理学杂志》 2024 (006)
864-868 / 5
武汉市卫健委中医药科研基金资助项目(WZ22C18)
10.13699/j.cnki.1001-6821.2024.06.017
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