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姜黄素抑制HMGB1-NF-κB信号通路减轻脂多糖诱导新生大鼠急性肺损伤实验研究 被引量:3

Curcumin alleviating lung inflammation in lipopolysaccharide-induced acute lung injury by inhibiting HMGB1-NF-κB signaling pathway in neonatal rats
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摘要 目的分析姜黄素抑制高迁移率族蛋白B1(HMGB1)-核转录因子κB(NF-κB)信号通路减轻脂多糖(LPS)诱导新生大鼠急性肺损伤(ALI)的作用。方法将60只新生SD雄性大鼠随机分为对照组、模型组、地塞米松(阳性药,2 mg·kg^(-1))组和姜黄素低、中、高剂量(1.5、3.0、6.0 mg·kg^(-1))组,每组10只。除对照组外,所有大鼠采用腹膜内注射LPS(3 mg·kg^(-1))建立ALI模型。注射LPS约6 h后开始ip给药,每天1次,连续7 d,模型组和对照组大鼠ip等体积的0.1%DMSO。通过血氧分压(PaO)和肺干湿质量比(W/D)评估新生大鼠肺水肿情况;HE染色检测各组大鼠肺组织损伤;ELISA法检测新生大鼠支气管肺泡灌洗液(BALF)氧化应激指标超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)、丙二醛(MDA)和谷胱甘肽(GSH)水平,BALF中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和HMGB1水平;Western blotting法检测大鼠肺组织胞核NF-κB、胞浆NF-κB和磷酸化核因子κB抑制因子α(p-IκBα)蛋白表达。结果与对照组相比,模型组新生大鼠肺泡腔有渗出、肺组织结构紊乱、细胞核固缩深染、伴随大量的炎性细胞浸润,病理评分显著升高(P<0.01);PaO、BALF中SOD和GSH水平显著降低(P<0.01);肺W/D,BALF中MPO和MDA水平,BALF中IL-6、TNF-α和HMGB1水平,NF-κB胞核/胞浆比例和胞浆p-IκBα蛋白表达水平显著升高(P<0.01)。与模型组相比,姜黄素高、中剂量组和地塞米松组大鼠肺组织病理损伤减轻,肺泡腔渗出、炎性细胞浸润明显减少,病理评分显著降低(P<0.05、0.01);PaO、BALF中SOD和GSH水平显著升高(P<0.05、0.01);肺W/D,BALF中MPO、MDA水平,BALF中IL-6、TNF-α和HMGB1水平,NF-κB胞核/胞浆比例和胞浆p-IκBα蛋白表达水平显著降低(P<0.05、0.01)。结论姜黄素可以通过抑制HMGB1-NF-κB信号通路减轻LPS诱导的新生大鼠ALI。 Objective To analyze the mechanism of curcumin on alleviating lung inflammation in lipopolysaccharide(LPS) induced acute lung injury(ALI) by inhibiting high mobility group B1(HMGB1)-nuclear factor κB(NF-κB) signaling pathway in neonatal rats. Methods Sixty neonatal male SD rats were randomly divided into control group, model group, dexamethasone(positive drug,2 mg·kg^(-1)) group and curcumin low-dose, medium-dose and high-dose(1.5, 3.0 and 6.0 mg·kg^(-1)) groups, with 10 rats in each group.ALI model was established by intraperitoneal injection of LPS(3 mg·kg^(-1)) in all rats except the control group. About 6 h after LPS injection, ip administration was started, once a day, for seven consecutive days, and 0.1% DMSO of equal volume was ip to rats in model group and control group. Lung edema of neonatal rats was evaluated by partial pressure of blood oxygen(PaO) and lung drywet weight ratio(W/D). HE staining was used to detect lung tissue injury. The levels of oxidative stress indexes [superoxide dismutase(SOD), myeloperoxidase(MPO), malondialdehyde(MDA), and glutathione(GSH)], interleukin 6(IL-6), tumor necrosis factor α(TNF-α) and high mobility group protein B1(HMGB1) in bronchoalveolar lavage fluid(BALF) were detected by ELISA.The expressions of nucleus NF-κB, cytoplasmic NF-κB and phosphorylated inhibitor of nuclear factor κBα(p-IκBα) in lung tissues were detected by Western blotting. Results Compared with control group, the alveolar cavity of neonatal rats in model group had exudation, lung tissue structure disorder, nuclear pyknosis and deep staining, accompanied by a large number of inflammatory cell infiltration, and the pathological score was significantly increased(P < 0.01). Compared with control group, PaOand the levels of SOD and GSH in BALF of rats in model group were significantly decreased(P < 0.01). Compared with control group, lung W/D,MPO and MDA levels in BALF, IL-6, TNF-α and HMGB1 levels in BALF, and nuclear/cytoplasmic ratio of NF-κB and cytoplasmic p-IκBα protein expression level were significantly increased of rats in model group(P < 0.01). Compared with model group, the lung pathological injury, alveolar exudation, inflammatory cell infiltration and pathological score of rats in curcumin high and medium-dose groups and dexamethasone group were significantly reduced(P < 0.05, 0.01). Compared with model group, PaOand the levels of SOD and GSH in BALF were significantly increased(P < 0.05, 0.01), lung W/D, the levels of MPO and MDA in BALF, the levels of IL-6, TNF-α and HMGB1 in BALF, the nuclear/cytosol ratio of NF-κB and the protein expression of p-IκBα in cytosol were significantly decreased(P < 0.05, 0.01) in curcumin high and medium-dose groups and dexamethasone group.Conclusion Curcumin can alleviate lung inflammation in LPS induced ALI model by inhibiting HMGB1-NF-κB signaling pathway in neonatal rats.
作者 樊黎丽 孟泳 赵润杨 王艳梅 唐引引 FAN Lili;MENG Yong;ZHAO Runyang;WANG Yanmei;TANG Yinyin(Department of Pulmonary Disease,Henan Hospital of Traditional Chinese Medicine(The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine),Zhengzhou 450002,China)
出处 《药物评价研究》 CAS 2022年第11期2224-2230,共7页 Drug Evaluation Research
基金 河南省中医管理局科研项目(2019JDZX057)。
关键词 姜黄素 急性肺损伤 HMGB1-NF-κB信号通路 炎症因子 氧化应激 curcumin acute lung injury HMGB1-NF-κB signaling pathway inflammatory factor oxidative stress
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