姜黄素对急性肺损伤小鼠肺组织转化生长因子-β1表达的影响

Effect of curcumin on transforming growth factor-β1 level in lung tissue of mice with acute lung injury

目的观察姜黄素对博莱霉素致急性肺损伤小鼠肺组织转化生长因子-β1（TGF-β1）表达的影响。方法昆明雄性小鼠60只，随机（随机数字法）分为假手术组，模型组，和姜黄素高、中、低剂量组，每组12只。除假手术组外其余各组小鼠气管内一次性滴注盐酸博莱霉素，假手术组一次性滴注等体积的生理盐水。造模后24h开始给药，持续到处死动物的前1d。姜黄素高、中、低剂量组给药剂量分别为200，100，50mg·kg^-1·d^-1，假手术组、模型组分别灌服等体积的生理盐水。各组动物分别于给药后第3天和第7天随机处死6只，取肺组织进行HE染色，观察肺组织形态学改变；检测肺湿干比值；同时进行免疫组化显色，检测各组小鼠肺组织中转化生长因子-β1的表达水平。数据以均数±标准差（-x±s）表示。采用SPSS11．5统计软件进行分析。多样本均数的比较采用单因素方差分析。结果假手术组小鼠未见明显形态学异常，肺泡内未见水肿液及炎性细胞；模型组肺组织毛细血管明显扩张充血，肺泡间隔增宽，肺泡腔内可见水肿液及大量炎性细胞浸润；姜黄素高、中、低剂量组也可见不同程度的病理改变，但与模型组比肺损伤程度明显减轻。模型组肺湿干比值较假手术组明显升高（P〈0．01），但姜黄素各剂量组湿干比值较模型组明显降低（P〈0．01）。假手术组肺组织TGF—β1呈低水平表达，模型组肺组织TGF—β1表达显著高于假手术组（P〈0．01）。姜黄素高、中、低剂量组肺组织TGF—β1蛋白表达较模型组明显降低（P〈0．01），但仍高于假手术组（P〈0．01）。结论姜黄素可抑制肺损伤小鼠肺组织中TGF—β1的表达，减轻肺损伤的程度，对急性肺损伤具有一定的保护作用，其保护机制可能是通过抑制肺组织中TGF—β1的表达来实现的。

Objective To observe the level of transforming growth factor-J31 （TGF-[31） in lung tissue of mice with acute lung injury induced by bleomycin. Methods Sixty Kunming male mice were randomly （random number） divided into sham operation group, model group, curcumin high dose group, medium dose group and low dose group （n = 12 in each group）. The models of acute lung injury were made by intratracheal instillation of bleomycin for once in the mice of model group and curcumin treated groups, and equal volume of saline was used in mice of sham operation group instead of bleomycin. Curcumin was given in doses of 200 mg . kg-1 . d-l, 100 mg. kg-1 . d-1and50 mg. kg-1 . d-1 to the mice of high dose group, medium dose group and low dose group, respectively 24 hours after modeling until the day before sacrifice, and the mice of sham operation group and model group were fed with equal volume of saline instead. Six mice of each group were sacrificed on the 3rd and 7th day separately for detecting lung wet to dry ratio （W/D）, pathological changes of lung tissue stained with HE, and level of the transforming growth factor-β1 in the lung tissues stained with immunohistochemistry in mice of each group. Data were analyzed to express as mean ± standard deviation. SPSS11.5 statistical package was used for analysis. The comparison of the mean diversity carried out by using single factor analysis of variance. Results Morphological changes in lung tissue observed under light microscope showed that obvious morphological abnormalities,alveolar edema fluid and inflammatory cells were not found in mice of sham operation group, and lung capillaries dilated, widened alveolar septum, edema fluid and inflammatory cells infiltration in the alveolar in lung tissue were seen in mice of model group, and different degrees of pathological changes were found in mice of three curcumin treated groups, but those changes were less severe than those in mice of model group. Lung wet to dry ratio （W/D） was significantly higher in mice of model group than that in mice of sham group （ P 〈 0. 01 ）, but that in mice of three curcumin treated groups was significantly lower than that in mice of model group （ P 〈 0. 01 ）. Immunohistochemistry showed low level of TGF-β1 in lung tissue of mice in sham operation group, and the level of TGF-β1 in lung tissue of mice in model group was significantly higher than that in sham operation group （ P 〈 0. 01 ）. The level of TGF-β1 in lung tissue of mice in three curcumin treated groups was significantly lower than that in mice of model group （ P 〈 0. 01 ）, but that was still higher than that in sham group （ P 〈 0. 01 ）. Conclusions Curcumin can inhibit the TGF-β1 in lung tissue and play a protective effect on acute lung injury induced by bleomycin, reducing the degree of lung injury. The protective mechanism may be associated with the inhibition of TGF-β1 in lung tissue.