摘要
目的探讨姜黄素对肺炎链球菌肺炎幼鼠肺组织损伤的改善作用及对沉默信息调节因子1(silent information regulator 1,SIRT1)/核因子E2相关因子2(nuclear factor E2-related factor 2,Nrf2)信号通路的影响。方法50只幼鼠随机分为正常组、模型组、低剂量组、高剂量组和头孢呋辛组,每组各10只。低、高剂量组幼鼠分别给予10、20 mg/kg姜黄素灌胃,头孢呋辛组幼鼠50 mg/kg头孢呋辛灌胃,模型组和正常组幼鼠等量生理盐水灌胃,1次/d,连续5天。于给药第3天,制备肺炎链球菌感染模型。除正常组外,其余组幼鼠经鼻腔滴注50μl肺炎链球菌悬液1×10^(6)CFU/ml,正常组滴注生理盐水。测定幼鼠肺功能、肺系数和肺湿干重比。酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)测定肺组织中肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)、白细胞介素6(interleukin 6,IL-6)和IL-1β含量。苏木精-伊红(hematoxylin-eosin,HE)染色法观察肺组织病理损伤。蛋白免疫印迹法(Western blot)检测SIRT1、Nrf2和血红素加氧酶1(heme oxygenase 1,HO-1)蛋白相对表达量。结果正常组幼鼠肺泡结构完整,未见炎性细胞浸润;模型组幼鼠肺泡间隔增厚,可见大量炎性细胞浸润;低、高剂量组和头孢呋辛组幼鼠肺泡间隔稍增厚,轻度炎症细胞浸润。与正常组比较,模型组幼鼠气道阻力(airway resistance,AR)、TNF-α、IL-6和IL-1β含量以及SIRT1、Nrf2和HO-1蛋白相对表达量升高,肺动态顺应性(pulmonary dynamic compliance,Cdyn)以及呼气峰值流速(peak expiratory flow,PEF)降低(P<0.05);与模型组比较,低、高剂量组和头孢呋辛组幼鼠AR、TNF-α、IL-6和IL-1β含量以及SIRT1、Nrf2和HO-1蛋白相对表达量降低,Cydn和PEF升高(P<0.05);与低剂量组比较,高剂量组和头孢呋辛组幼鼠AR、TNF-α、IL-6和IL-1β含量以及SIRT1、Nrf2和HO-1蛋白相对表达量降低,Cydn和PEF升高(P<0.05);与高剂量组比较,头孢呋辛组幼鼠AR、TNF-α、IL-6和IL-1β含量以及SIRT1、Nrf2和HO-1蛋白相对表达量降低,Cydn和PEF升高(P<0.05)。结论姜黄素可改善肺炎链球菌肺炎幼鼠肺组织损伤,减轻炎症反应,其可能是通过抑制SIRT1/Nrf2信号通路。
Objective To investigate the ameliorative effect of curcumin on lung tissue injury of mice of streptococcus pneumonia and its effect on silent information regulator 1(SIRT1)/nuclear factor E2-related factor 2(Nrf2)signaling pathway.Methods A total of 50 mice were randomly divided into the normal group,model group,low dose group,high dose group and cefuroxime group,with 10 in each group.Low and high dose group were respectively given 10 and 20 mg/kg of curcumin by lavage,and cefuroxime group was given cefuroxime 50 mg/kg by lavage;model group and normal group were given same amount of normal saline by lavage,one time each day for consecutive five days.On the 3 rd day after administration,the streptococcus pneumonia infected models were constructed.Except for the normal group,mice in other groups were given 50μl streptococcus pneumoniae suspension 1×10^(6)CFU/ml by nasal drip,and normal group was given normal saline.Lung function,lung coefficient and wet-dry weight ratio were measured,tumor necrosis factor alpha(TNF-α),interleukin 6(IL-6)and IL-1β in lung tissue were determined by enzyme-linked immunosorbent assay(ELISA),and pathological injury of lung tissue was observed by hematoxylin-eosin(HE)staining.The relative expression levels of SIRT1,Nrf2 and heme oxygenase 1(HO-1)proteins were detected by Western blot.Results The alveolar structure of the normal group was intact without inflammatory cell infiltration.In model group,alveolar septums of mice were thickened and a large number of inflammatory cells were visible.Alveolar septums were slightly thickened and inflammatory cells infiltrated slightly in mice in the low,high dose and cefuroxime groups.Compared with normal group,the contents of airway resistance(AR),TNF-α,IL-6 and IL-1β,and the relative expression levels of SIRT1,Nrf2 and HO-1 proteins were increased in model group,while the pulmonary dynamic compliance(Cydn)and peak expiration flow(PEF)were decreased(P<0.05).Compared with model group,the contents of AR,TNF-α,IL-6 and IL-1β,and the relative expressions of SIRT1,Nrf2 and HO-1 proteins were decreased in low dose,high dose and cefuroxime groups,while Cydn and PEF were increased(P<0.05).Compared with the low dose group,the contents of AR,TNF-α,IL-6 and IL-1β,and the relative expressions of SIRT1,Nrf2 and HO-1 proteins in the high dose group and cefuroxime group were decreased,while Cydn and PEF were increased(P<0.05).Compared with low dose group,the contents of AR,TNF-α,IL-6 and IL-1β as well as the relative expression levels of SIRT1,Nrf2 and HO-1 proteins in high dose and cefuroxime groups were decreased,while Cydn and PEF were increased(P<0.05).Compared with the high dose group,the contents of AR,TNF-α,IL-6 and IL-1β as well as the relative expression levels of SIRT1,Nrf2 and HO-1 proteins in cefuroxime group were decreased,while Cydn and PEF were increased(P<0.05).Conclusion Curcumin can improve lung tissue injury and reduce inflammatory response in mice with streptococcus pneumonia,possibly by inhibiting SIRT1/Nrf2 signaling pathway.
作者
张鹏
张宇晨
王润智
ZHANG Peng;ZHANG Yuchen;WANG Runzhi(Department of Pediatrics,General Hospital of Pingmei Shenma Medical Group,Pingdingshan Henan 467000,China)
出处
《华南国防医学杂志》
CAS
2021年第11期781-785,共5页
Military Medical Journal of South China
基金
中华国际科学交流基金会检验检测科技专项基金(Z2019LHNB019)。
关键词
肺炎
肺炎链球菌
姜黄素
SIRT1/Nrf2信号通路
Pneumonia
Streptococcus
Curcumin
Silent information regulator 1/nuclear factor E2-related factor 2 signaling pathway
