姜黄素通过增强自噬水平抑制急性肺损伤大鼠肺组织炎症反应  

Curcumin inhibiting inflammation in lung tissue via enhancing autophagy level after acute lung injury in rats

作　　者：史妍[1] 解东兴[1] 刘伟[1] 李莉[1] 凌腾涛 SHI Yan;XIE Dong-xing;LIU Wei;LI Li;LING Teng-tao(Tangshan Gongren Hospital,Tangshan,Hebei 063000,China)

机构地区：[1]唐山市工人医院,河北唐山063000

出　　处：《现代预防医学》2021年第6期1089-1093,共5页Modern Preventive Medicine

基　　金：河北省唐山市科技局指令性项目(12140210A-11)。

摘　　要：目的观察脂多糖(LPS)诱导的急性肺损伤(ALI)大鼠模型肺组织中自噬表达,探讨姜黄素是否通过上调急性肺损伤大鼠自噬水平抑制肺组织的炎症反应。方法40只雄性SD大鼠随机分为对照组、急性肺损伤组(ALI组)、姜黄素组、自噬抑制剂3-甲基腺嘌呤组(3-MA组)。采用一次性气管内滴注LPS(4 mg/kg)制备ALI大鼠模型。姜黄素组与3-MA组于造模前15 min分别腹腔注射姜黄素(200 mg/kg)或自噬抑制剂3-MA(15 mg/kg)。于造模后24 h取材HE染色观察肺组织形态变化;ELISA法测定支气管肺泡灌洗液中(BALF)中细胞总数及肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)及白介素-6(IL-6)的含量;real-time PCR检测自噬基因ATG5、ATG7的m RNA水平;western blot法检测自噬标志蛋白微管相关蛋白1轻链3(LC-3)、Beclin-1。结果与对照组相比,ALI组大鼠肺组织中大量炎症细胞浸润,BALF中细胞总数增加,TNF-α、IL-1β及IL-6水平较对照组显著上调(P<0.05),自噬指标ATG5、ATG7m RNA水平与LC-3、Beclin-1蛋白表达量明显上调(P<0.05)。与ALI组相比,姜黄素组炎症细胞浸润减轻,BALF中细胞总数减少,TNF-α、IL-1β及IL-6水平显著减少(P<0.05),自噬相关基因和蛋白表达进一步上调(P<0.05)。3-MA处理显著抑制自噬相关指标的表达,加重炎症细胞浸润,增多BALF中TNF-α、IL-1β的含量(P<0.05)。结论姜黄素处理通过进一步增强ALI的细胞自噬水平减轻大鼠肺组织的炎症损伤,进而发挥保护性疗效。Objective To investigate whether curcumin inhibits the inflammatory response of lung tissues through upregulating the level of autophagy in rats with acute lung injury through assessing the autophagy level in the lung tissue in lipopolysaccharide(LPS)-induced acute lung injury(ALI)model.Methods Forty male SD rats were randomly divided into control group,ALI group,curcumin group and autophagy inhibitor 3-methyladenine group(3-MA group).The ALI rat model was prepared using a single intratracheal drip of LPS(4 mg/kg).Curcumin(200 mg/kg)or autophagy inhibitor 3-MA(15 mg/kg)was injected intraperitoneally into the curcumin and 3-MA groups respectively 15 min before modeling.The morphological changes of lung tissues were observed by HE staining at 24 h post-modeling.ELISA analysis was engaged to detect the total number of cells and the content of TNF-α,IL-1βand IL-6 in the BALF.The mRNA levels of ATG5 and ATG7 were measured with Real-time PCR.Autophagy marker proteins microtubule-associated protein 1 light chain 3(LC-3)and Beclin-1 were measured by Western blot.Results Compared with control group,the ALI group showed a large infiltration of inflammatory cells in the lung tissue,an increase in the total number of cells in the BALF,a significant upregulation of TNF-α,IL-1βand IL-6 levels compared with the control group(P<0.05),and a notable upregulation of autophagy indexes ATG5 and ATG7 mRNA levels and LC-3 and Beclin-1 protein expression(P<0.05).Compared with the ALI group,the curcumin group showed less infiltration of inflammatory cells,decreased total number of cells in BALF,significantly reduced levels of TNF-α,IL-1βand IL-6(P<0.05),and further upregulation of the expression of autophagy-related genes and proteins(P<0.05).3-MA treatment significantly inhibited the expression of autophagy-related indicators,aggravated the infiltration of inflammatory cells,and increased the levels of TNF-αand IL-1βin BALF(P<0.05).Conclusion Curcumin could provide the protective effects against LPS-induced inflammatory injury t

关 键 词：急性肺损伤 姜黄素 3-甲基腺嘌呤 自噬 炎症 

分 类 号：R285.5[医药卫生—中药学]