姜黄素对急性呼吸窘迫综合征大鼠肺组织及气道重塑的影响

doi:10.3877/cma.j.issn.1674-6880.2021.05.004

中华危重症医学杂志(电子版) ›› 2021, Vol. 14 ›› Issue (05) : 368 -373. doi: 10.3877/cma.j.issn.1674-6880.2021.05.004

论著

姜黄素对急性呼吸窘迫综合征大鼠肺组织及气道重塑的影响

杨茂宪¹, 姚明²^,^†(

), 徐龙生³, 沈鹏¹, 陈文宇⁴, 王倩倩¹, 施云超¹

^1. 314001　浙江嘉兴，嘉兴学院附属医院　嘉兴市第一医院重症医学科
^2. 314001　浙江嘉兴，嘉兴学院附属医院　嘉兴市第一医院麻醉科
^3. 314001　浙江嘉兴，嘉兴学院附属医院　嘉兴市第一医院中心实验室
^4. 314001　浙江嘉兴，嘉兴学院附属医院　嘉兴市第一医院呼吸科

收稿日期:2021-01-30 出版日期:2021-10-31
通信作者: 姚明
基金资助:
浙江省嘉兴市科技应急攻关项目(2020GZ30001); 浙江省嘉兴市医学重点学科-麻醉学（支撑学科）(2019-zc-06); 浙江省嘉兴市医学重点学科-重症医学（支撑学科）(2019-zc-12); 2020年高校直属附属医院抗疫专项项目(Y202043750)

Effect of curcumin pretreatment on lung tissue and airway remodeling in acute respiratory distress syndrome rats

Maoxian Yang¹, Ming Yao²^,^†(), Longsheng Xu³, Peng Shen¹, Wenyu Chen⁴, Qianqian Wang¹, Yunchao Shi¹

^1. Department of Critical Care Medicine, Affiliated Hospital of Jiaxing University, the First Hospital of Jiaxing, Jiaxing 314001, China
^2. Department of Anesthesiology, Affiliated Hospital of Jiaxing University, the First Hospital of Jiaxing, Jiaxing 314001, China
^3. Department of Central Laboratory, Affiliated Hospital of Jiaxing University, the First Hospital of Jiaxing, Jiaxing 314001, China
^4. Department of Respiratory Medicine, Affiliated Hospital of Jiaxing University, the First Hospital of Jiaxing, Jiaxing 314001, China

Received:2021-01-30 Published:2021-10-31
Corresponding author: Ming Yao

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引用本文：

杨茂宪, 姚明, 徐龙生, 沈鹏, 陈文宇, 王倩倩, 施云超. 姜黄素对急性呼吸窘迫综合征大鼠肺组织及气道重塑的影响[J]. 中华危重症医学杂志(电子版), 2021, 14(05): 368-373.

Maoxian Yang, Ming Yao, Longsheng Xu, Peng Shen, Wenyu Chen, Qianqian Wang, Yunchao Shi. Effect of curcumin pretreatment on lung tissue and airway remodeling in acute respiratory distress syndrome rats[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2021, 14(05): 368-373.

目的

探讨姜黄素对气管内雾化脂多糖诱导的急性呼吸窘迫综合征（ARDS）大鼠肺组织纤维化及支气管杯状细胞的影响。

方法

将24只Sprague Dawley成年雄性大鼠分为对照组（仅气管内雾化等容积等渗NaCl溶液）、ARDS组（气管内雾化脂多糖4 mg/kg）、姜黄素组（复制ARDS模型30 min前腹腔注射姜黄素50 mg/kg），每组各8只。模型复制5 d后计算各组大鼠肺组织湿干重比值（W/D）、支气管肺泡灌洗液（BALF）中肿瘤坏死因子α（TNF-α）、Ⅲ型前胶原（PCⅢ）的含量。Western-blotting检测各组大鼠肺组织Toll样受体4（TLR4）及核因子κBp65（NF-κBp65）蛋白表达水平。同时，采用Masson染色观察肺组织胶原纤维分布，阿利新蓝-过碘酸-雪夫（AB-PAS）染色观察支气管杯状细胞和黏液的情况。

结果

各组大鼠肺组织W/D，BALF中TNF-α、PCⅢ的含量，肺组织NF-κBp65及TLR4蛋白表达的比较，差异均有统计学意义（F = 136.155、139.639、95.353、94.034、67.540，P均< 0.001）。且与对照组比较，ARDS组和姜黄素组肺组织W/D[（3.99 ± 0.16）、（5.53 ± 0.15）、（4.81 ± 0.24）]，BALF中的TNF-α[（61 ± 5）、（219 ± 25）、（157 ± 21）ng/L]和PCⅢ[（0.67 ± 0.22）、（61.66 ± 11.95）、（35.62 ± 9.64）μg/L]含量，肺组织中NF-κBp65及TLR4蛋白表达水平均显著升高，且ARDS组更高（P均< 0.05）。Masson染色显示，ARDS组肺间质呈广泛胶原纤维沉积，姜黄素组肺间质呈轻度弥漫性胶原纤维沉积。AB-PAS染色可见，ARDS组支气管上皮杯状细胞化生、姜黄素组支气管上皮杯状细胞轻度化生。

结论

姜黄素可以逆转脂多糖诱导的ARDS大鼠气道杯状细胞化生，改善肺组织纤维化，可能与抑制TLR4/NF-κB信号通路、改善肺部炎症反应有关。

关键词: 姜黄素, 呼吸窘迫综合征，成人, 大鼠

Objective

To investigate the effect of curcumin pretreatment on pulmonary fibrosis and goblet cells in rats with acute respiratory distress syndrome (ARDS) induced by intratracheal aerosol lipopolysaccharide (LPS).

Methods

A total of 24 adult male Sprague Dawley rats were randomly divided into 3 groups: the control group (intratracheal aerosol of isotonic NaCl solution), ARDS group (intratracheal aerosol of LPS 4 mg/kg) and curcumin group (intraperitoneal injection of curcumin 50 mg/kg 30 min before aerosol of LPS 4 mg/kg), 8 rats in each group. The ratio of wet to dry weight (W/D) in lung tissue and the contents of tumor necrosis factor-alpha (TNF-α) and type Ⅲ procollagen (PCⅢ) in bronchoalveolar lavage fluid were calculated after 5 d of modeling in each group. The protein expression levels of Toll-like receptor 4 (TLR4) and nuclear factor-kappa Bp65 (NF-κBp65) in lung tissue were detected by Western-blotting. The distribution of collagen fibers was observed by Masson staining and the goblet cells and mucus were observed by alcian blue-periodic acid schiff (AB-PAS) staining.

Results

The W/D, TNF-α, PCⅢ, TLR4 protein and NF-κBp65 protein among the three group all showed significant differences (F = 136.155, 139.639, 95.353, 94.034, 67.540; all P<0.001). Compared with the control group, the W/D [(3.99 ± 0.16), (5.53 ± 0.15), (4.81 ± 0.24)], TNF-α [(61 ± 5), (219 ± 25), (157 ± 21) ng/L], PCⅢ [(0.67 ± 0.22), (61.66 ± 11.95), (35.62 ± 9.64) μg/L], TLR4 protein and NF-κBp65 protein increased obviously in the ARDS and curcumin groups, and they increased most in the ARDS group (all P < 0.05). Masson staining showed extensive collagen deposition in the ARDS group and mild diffuse collagen deposition in the curcumin group. AB-PAS staining showed goblet cell metaplasia in the ARDS group and mild goblet cell metaplasia in the curcumin group.

Conclusion

Curcumin can reverse goblet cell metaplasia and pulmonary fibrosis in LPS-induced ARDS rats, which may be related to improving lung inflammatory responses by inhibiting the TLR4/NF-κB pathway.

Key words: Curcumin, Respiratory distress syndrome, adult, Rats

表1 各组大鼠肺组织W/D及BALF中TNF-α、PCⅢ水平的比较（±s）

组别	只数	W/D	TNF-α（ng/L）	PCⅢ（(μg/L）
对照组	8	3.99 ± 0.16	61 ± 5	0.67 ± 0.22
ARDS组	8	5.53 ± 0.15^a	219 ± 25^a	61.66 ± 11.95^a
姜黄素组	8	4.81 ± 0.24^ab	157 ± 21^ab	35.62 ± 9.64^ab
F值		136.155	139.639	95.353
P值		<0.001	<0.001	<0.001

表1 各组大鼠肺组织W/D及BALF中TNF-α、PCⅢ水平的比较（±s）

组别	只数	W/D	TNF-α（ng/L）	PCⅢ（(μg/L）
对照组	8	3.99 ± 0.16	61 ± 5	0.67 ± 0.22
ARDS组	8	5.53 ± 0.15^a	219 ± 25^a	61.66 ± 11.95^a
姜黄素组	8	4.81 ± 0.24^ab	157 ± 21^ab	35.62 ± 9.64^ab
F值		136.155	139.639	95.353
P值		<0.001	<0.001	<0.001

图1 各组大鼠肺组织中NF-κBp65及TLR4蛋白表达水平的比较（n = 8）

图2 各组大鼠肺组织病理变化

图3 各组大鼠肺组织支气管病理变化

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