目的 分析姜黃素抑制高遷移率族蛋白B1（HMGB1）-核轉(zhuǎn)錄因子κB（NF-κB）信號(hào)通路減輕脂多糖（LPS）誘導(dǎo)新生大鼠急性肺損傷（ALI）的作用。方法 將60只新生SD雄性大鼠隨機(jī)分為對(duì)照組、模型組、地塞米松（陽(yáng)性藥，2 mg·kg^-1）組和姜黃素低、中、高劑量（1.5、3.0、6.0 mg·kg^-1）組，每組10只。除對(duì)照組外，所有大鼠采用腹膜內(nèi)注射LPS （3 mg·kg^-1）建立ALI模型。注射LPS約6 h后開(kāi)始ip給藥，每天1次，連續(xù)7 d，模型組和對(duì)照組大鼠ip等體積的0.1% DMSO。通過(guò)血氧分壓（PaO₂）和肺干濕質(zhì)量比（W/D）評(píng)估新生大鼠肺水腫情況；HE染色檢測(cè)各組大鼠肺組織損傷；ELISA法檢測(cè)新生大鼠支氣管肺泡灌洗液（BALF）氧化應(yīng)激指標(biāo)超氧化物歧化酶（SOD）、髓過(guò)氧化物酶（MPO）、丙二醛（MDA）和谷胱甘肽（GSH）水平，BALF中白細(xì)胞介素-6（IL-6）、腫瘤壞死因子-α（TNF-α）和HMGB1水平；Western blotting法檢測(cè)大鼠肺組織胞核NF-κB、胞漿NF-κB和磷酸化核因子κB抑制因子α（p-IκBα）蛋白表達(dá)。結(jié)果 與對(duì)照組相比，模型組新生大鼠肺泡腔有滲出、肺組織結(jié)構(gòu)紊亂、細(xì)胞核固縮深染、伴隨大量的炎性細(xì)胞浸潤(rùn)，病理評(píng)分顯著升高（P<0.01）； PaO₂、BALF中SOD和GSH水平顯著降低（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/胞漿比例和胞漿p-IκBα蛋白表達(dá)水平顯著升高（P<0.01）。與模型組相比，姜黃素高、中劑量組和地塞米松組大鼠肺組織病理?yè)p傷減輕，肺泡腔滲出、炎性細(xì)胞浸潤(rùn)明顯減少，病理評(píng)分顯著降低（P<0.05、0.01）； PaO₂、BALF中SOD和GSH水平顯著升高（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/胞漿比例和胞漿p-IκBα蛋白表達(dá)水平顯著降低（P<0.05、0.01）。結(jié)論 姜黃素可以通過(guò)抑制HMGB1-NF-κB信號(hào)通路減輕LPS誘導(dǎo)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 (PaO₂) 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, PaO₂ and 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, PaO₂ and 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.

R285.5

河南省中醫(yī)管理局科研項(xiàng)目（2019JDZX057）