Zhang De-ping, Qiu Hui, Zhuang Yi, Meng Fan-qing
Department of Respiratory Medicine, Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2007 Mar;30(3):197-201.
To observe the effect and mechanism of curcumin on pulmonary fibrosis induced by bleomycin in rats.
Fifty-four SD rats were randomly divided into 3 groups, 18 rats each group. The control group received a single intratracheal dose of 2 ml/kg of sterile physiological saline at day 0, and from 14 d, 0.5 ml/kg of sterile physiological saline intraperitoneally every day. The bleomycin group received a single intratracheal dose of 5 mg/kg of bleomycin A(5), and from 14 d, 0.5 ml/kg of suspension of 6% alcohol and 6% polyethylene glycol intraperitoneally every day. The curcumin group received a single intratracheal dose of 5 mg/kg of bleomycin A(5), and from 14 d, 50 mg/kg of curcumin (suspended in 6% alcohol and 6% polyethylene glycol) intraperitoneally every day. Six rats in each group were killed at day 17, 21, 28 in batches. The sections of lungs were stained with hematoxylin-eosin (HE) and Masson's trichrome to evaluate the severity of alveolitis and pulmonary fibrosis. The content of hydroxyproline and the expression of transforming growth factor-beta(1) (TGF-beta(1)) mRNA, interferon-gamma (IFN-gamma) mRNA in lung tissues were analyzed. The concentration of TGF-beta(1) and IFN-gamma in bronchoalveolar lavage fluid (BALF) were measured.
(1) The scores of alveolitis in the curcumin group and the bleomycin group at day 28 were 1.3 +/- 0.5, 2.0 +/- 0.9, respectively, the difference being significant (q = 3.26, P < 0.05). (2) The scores of pulmonary fibrosis in the curcumin group and the bleomycin group were 1.3 +/- 0.5, 1.8 +/- 0.4 at day 21, and 1.2 +/- 0.4, 2.2 +/- 1.0 at day 28, the difference being significant between the two groups (q = 3.33, 4.00, all P < 0.05). (3) The content of hydroxyproline in lung tissues in the curcumin group and the bleomycin group were (1.75 +/- 0.36) microg/g, (2.47 +/- 0.24) microg/g at day 28, the difference being significant (q = 7.20, P < 0.01). (4) The concentration of TGF-beta(1) in BALF in the curcumin group and the bleomycin group were (20 +/- 3) ng/L, (39 +/- 7) ng/L at day 21, and (24 +/- 4) ng/L, (40 +/- 7) ng/L at day 28, all being statistically different between the two groups (q = 5.30, 6.27, all P < 0.05). (5) The expression of TGF-beta(1) mRNA in lung tissues in the curcumin group and the bleomycin group were 0.51 +/- 0.11, 0.59 +/- 0.13 at day 21, and 0.50 +/- 0.07, 0.64 +/- 0.11 at day 28, all being not statistically different between the two groups (q = 1.55, 3.13, all P > 0.05). (6) The concentrations of IFN-gamma in BALF in the curcumin group and the bleomycin group were 0.49 +/- 0.17, 0.50 +/- 0.08 at day 21, and 0.52 +/- 0.15, 0.52 +/- 0.11 at day 28, all being not statistically different between the two groups (q = 1.85, 2.03, all P > 0.05). (7) The expression of IFN-gamma mRNA in the curcumin group and the bleomycin group were (28 +/- 5) ng/L, (35 +/- 13) ng/L at day 21, and (30 +/- 11) ng/L, (39 +/- 13) ng/L at day 28, no significant difference between the two groups (q = 0.17, 0.00, all P > 0.05).
Curcumin can alleviate alveolitis and pulmonary fibrosis induced by bleomycin in rats, possibly through its inhibition of TGF-beta(1).
观察姜黄素对博来霉素诱导的大鼠肺纤维化的影响及其机制。
54只SD大鼠随机分为3组，每组18只。对照组于第0天经气管内给予2 ml/kg无菌生理盐水，从第14天起，每天腹腔注射0.5 ml/kg无菌生理盐水。博来霉素组于第0天经气管内给予5 mg/kg博来霉素A（5），从第14天起，每天腹腔注射0.5 ml/kg 6%乙醇和6%聚乙二醇混悬液。姜黄素组于第0天经气管内给予5 mg/kg博来霉素A（5），从第14天起，每天腹腔注射50 mg/kg姜黄素（混悬于6%乙醇和6%聚乙二醇中）。每组分别于第17、21、28天分批处死6只大鼠。取肺组织切片，进行苏木精-伊红（HE）染色和Masson三色染色，以评估肺泡炎和肺纤维化的严重程度。分析肺组织中羟脯氨酸含量以及转化生长因子-β1（TGF-β1）mRNA、干扰素-γ（IFN-γ）mRNA的表达。检测支气管肺泡灌洗液（BALF）中TGF-β1和IFN-γ的浓度。
（1）姜黄素组和博来霉素组第28天的肺泡炎评分分别为1.3±0.5、2.0±0.9，差异有统计学意义（q = 3.26，P < 0.05）。（2）姜黄素组和博来霉素组第21天的肺纤维化评分分别为1.3±0.5、1.8±0.4，第28天分别为1.2±0.4、2.2±1.0，两组间差异有统计学意义（q = 3.33、4.00，均P < 0.05）。（3）姜黄素组和博来霉素组第28天肺组织中羟脯氨酸含量分别为（1.75±0.36）μg/g、（2.47±0.24）μg/g，差异有统计学意义（q = 7.20，P < 0.01）。（4）姜黄素组和博来霉素组第21天BALF中TGF-β1浓度分别为（20±3）ng/L、（39±7）ng/L，第28天分别为（24±4）ng/L、（40±7）ng/L，两组间均有统计学差异（q = 5.30、6.27，均P < 0.05）。（5）姜黄素组和博来霉素组第21天肺组织中TGF-β1 mRNA表达分别为0.51±0.11、0.59±0.13，第28天分别为0.50±0.07、0.64±0.11，两组间均无统计学差异（q = 1.55、3.13，均P > 0.05）。（6）姜黄素组和博来霉素组第21天BALF中IFN-γ浓度分别为0.49±0.17、0.50±0.08，第28天分别为0.52±0.15、0.52±0.11，两组间均无统计学差异（q = 1.85、2.03，均P > 0.05）。（7）姜黄素组和博来霉素组第21天IFN-γ mRNA表达分别为（28±5）ng/L、（35±13）ng/L，第28天分别为（30±11）ng/L、（39±13）ng/L，两组间无显著差异（q = 0.17、0.00，均P > 0.05）。
姜黄素可减轻博来霉素诱导的大鼠肺泡炎和肺纤维化，可能是通过抑制TGF-β1实现的。
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