标准桃金娘油对慢性阻塞性肺疾病大鼠Nrf2/HO-1通路的影响

Study on the effect of standardized myrtle on Nrf2/HO-1 pathway in chronic obstructive pulmonary disease rats

目的:观察标准桃金娘油(myrtol standardized, MS)对慢性阻塞性肺疾病(COPD)大鼠核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)通路的影响,探讨标准桃金娘油治疗COPD可能的作用机制。方法:将Wistar大鼠随机分为4组,1组为空白对照组(CON),另外3组首先使用香烟(CS)慢性暴露90 d建立COPD模型,1组给予持续CS暴露(CSM)、1组停止CS暴露(QSM)、1组停止CS暴露并给予MS处理(MSM),持续30 d。造模结束后,分别检测大鼠呼吸功能、血清炎症因子[白介素6(IL6)和肿瘤坏死因子-α(TNF-α)]、肺组织抗氧化应激指标[总超氧化物歧化酶(T-SOD)和丙二醛(MDA)]、肺组织HE染色观察、蛋白质印迹(WB)检测肺组织Nrf2和HO-1蛋白表达。结果:CSM组呼吸功能明显减退(P<0.05),QSM和MSM组呼吸功能有所改善(P<0.05);MSM组的IL6和TNF-α显著低于CSM组(P<0.05),T-SOD显著升高(P<0.05),MDA显著下降(P<0.05);HE染色可见CSM组出现肺气肿样改变,MSM组可见肺组织结构异常的改善;同时MSM组Nrf2和HO-1蛋白表达相对于CSM和QSM组升高(P<0.05),接近于CON组(P>0.05)。结论:MS可显著改善COPD大鼠的呼吸功能、减少炎症浸润、减弱氧化应激,其内在机制与Nrf2/HO-1通路激活密切相关。

Objective: To observe the influence of myrtol standardized(MS) on the Nrf2/HO-1 pathway in chronic obstructive pulmonary disease(COPD) rats, and explore the possible mechanism of MS in treating COPD. Methods: Wistar rats were randomly divided into four groups: one was control group(CON), while the other three groups were exposed to cigarettes(CS) for 90 d to establish a COPD model firstly, then one group was given CS exposure(CSM) continuously, one group was quitted CS exposure(QSM), the other one group was quitted CS exposure and then given MS treatment(MSM), all the operations lasted for 30 d. After the modeling, the respiratory function, serum inflammatory factors(IL6, TNF-α), and lung tissue anti-oxidative stress indicators(T-SOD, MDA) were detected, HE staining of lung tissue was observed, and the expressions of Nrf2 and HO-1 in lung tissue by WB were analyzed. Results: The respiratory function of the CSM group decreased significantly(P<0.05), and the respiratory function of the QSM and MSM groups improved(P<0.05);the IL6 and TNF-α levels of the MSM group were significantly lower than those of the CSM group(P<0.05), and the T-SOD level increased(P<0.05), MDA decreased(P<0.05);HE staining showed emphysema-like forms in the lung tissues of the CSM group, MSM group could improve the abnormal structure of lung tissue. Meanwhile, the expressions of Nrf2 and HO-1 protein in the MSM group were relatively increased than the CSM and QSM groups(P<0.05), which was close to the CON group(P>0.05). Conclusion: MS could significantly improve the respiratory function of COPD rats, reduce inflammation and infiltration, and weaken oxidative stress. Its internal mechanism is closely related to the activation of the Nrf2/HO-1 pathway.