目的 研究姜黃素對百草枯所致小鼠肺纖維化的影響，并探討其保護(hù)機(jī)制。方法 將60只雄性昆明小鼠隨機(jī)分為對照組、模型組及姜黃素20、40、80 mg/kg干預(yù)組和地塞米松5 mg/kg組，每組10只。制備小鼠肺纖維化模型的同時ig給藥，對照組和模型組ig 0.1 mL的0.9%的生理鹽水，每2天給藥1次，第28天眼球取血后處死所有小鼠。取左側(cè)肺組織制作組織切片進(jìn)行HE染色和Masson染色，右側(cè)肺組織進(jìn)行羥脯氨酸（HYP）、丙二醛（MDA）以及超氧化物歧化酶（SOD）測定。采用酶聯(lián)免疫吸附法（ELISA）測定血清中腫瘤壞死因子-α（TNF-α）、白介素-6（IL-6）、基質(zhì)金屬蛋白酶9（MMP-9）水平。通過免疫組化分析肺組織中核因子NF-κB表達(dá)水平。結(jié)果 姜黃素20、40、80 mg/kg干預(yù)組及地塞米松組的肺纖維化程度明顯輕于模型組。與模型組比較，姜黃素各劑量組和地塞米松組HYP及MDA水平均顯著降低，而SOD含量顯著升高（P<0.01）；與地塞米松組比較，姜黃素40、80 mg/kg干預(yù)組MDA水平顯著降低（P<0.05），姜黃素80 mg/kg干預(yù)組的SOD水平顯著升高（P<0.05）。與模型組相比，姜黃素20、40、80 mg/kg干預(yù)組和地塞米松組血清中的TNF-α、IL-6、MMP-9濃度降低明顯（P<0.01），且姜黃素40、80 mg/kg干預(yù)組的TNF-α、MMP-9水平低于地塞米松組（P<0.05）。與模型組比較，姜黃素20、40、80 mg/kg干預(yù)組和地塞米松組肺組織細(xì)胞核NF-κB表達(dá)水平顯著降低（P<0.01）。結(jié)論 姜黃素可有效降低肺纖維化模型小鼠HYP、MDA含量、血清中TNF-α、IL-6濃度，下調(diào)肺組織NF-κB蛋白表達(dá)水平，改善肺部形態(tài)學(xué)病變，增強(qiáng)抗氧化能力，對肺纖維化小鼠產(chǎn)生保護(hù)作用。

Objective To investigate the effects of curcumin on paraquat-induced pulmonary fibrosis in mice and explore its protective mechanism. Methods 60 male Kunming mice were randomly divided into control group, model group, curcumin 20, 40, 80 mg/kg intervention group and dexamethasone group, each group had 10 mice. The pulmonary fibrosis model of mice was prepared by intragastric administration. The control group and the model group were ig administered with 0.9% saline 0.1 mL, once every 2 days, and all mice were killed on the 28th day after eyeball blood was taken. The left pulmonary was carried out for HE staining and Masson staining, and the right pulmonary was used for the detection of HYP, MDA, and SOD. Serum levels of TNF-α, IL-6, and MMP-9 were determined by ELISA. Immunohistochemistry was performed to analyze the expression level of nuclear factor NF-κB in lung tissues. Results The degree of pulmonary fibrosis in the curcumin 20, 40, 80 mg/kg intervention group and dexamethasone group were significantly less than that in the model group. Compared with model group, HYP and MDA levels of curcumin in each dose group and dexamethasone group were significantly reduced, while SOD was significantly increased (P<0.01). Compared with dexamethasone group, MDA level in curcumin 40 and 80 mg/kg intervention group was significantly reduced (P<0.05), while SOD level in curcumin 80 mg/kg intervention group was significantly increased (P<0.05). Compared with model group, the serum concentrations of TNF-α, IL-6, and MMP-9 in the 20, 40 and 80 mg/kg intervention group and dexamethasone group were significantly decreased (P<0.01), and the levels of TNF-α and MMP-9 in the 40 and 80 mg/kg intervention group were lower than those in the dexamethasone group (P<0.05). Compared with the model group, the expression level of nuclear NF-κB was significantly decreased in the intervention group with curcumin at 20, 40 and 80 mg/kg and the dexamethasone group (P<0.01). Conclusion Curcumin can effectively reduce the content of HYP and MDA, as well as the concentrations of TNF-α and IL-6 in serum of pulmonary fibrosis model mice, down-regulate the expression level of NF-κB protein in lung tissues, improve lung morphological lesions, enhance antioxidant ability, and have a protective effect on pulmonary fibrosis mice.

國家自然科學(xué)基金項目（No.31271475）