| 江端,刘奥杰,凌伟.姜黄素减轻脓毒症大鼠肺损伤的作用机制[J].安徽医药,2022,26(9):1706-1710. |
| 姜黄素减轻脓毒症大鼠肺损伤的作用机制 |
| Action mechanism of curcumin on relieving lung injury in sepsis rats |
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| DOI：10.3969/j.issn.1009-6469.2022.09.003 |
| 中文关键词: 姜黄素 肺损伤 脓毒症 丝裂原细胞外信号调节激酶/胞外信号调节激酶信号通路 机制 大鼠，Sprague-Dawley |
| 英文关键词: Curcumin Lung injury Sepsis MEK/ERK signaling pathway Mechanism Rats, Sprague-Dawley |
| 基金项目: |
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| 中文摘要: |
| 目的分析姜黄素减轻脓毒症大鼠肺损伤的作用机制。方法2018年8月至2019年4月，采用随机数字表法，将75只雄性SD大鼠分为五组，分别为假手术组，脓毒症组，姜黄素低、中、高剂量组，每组15只。通过盲肠结扎穿孔术构建脓毒症大鼠模型，假手术组仅开腹取出盲肠再原位放回，姜黄素低、中、高剂量组分别于术后腹腔注射剂量为50、100、200 mg/kg的姜黄素，假手术组和脓毒症组大鼠以等量生理盐水替代。采用苏木精-伊红(HE)染色观察各组大鼠肺组织学形态变化，以肺湿干比、支气管灌洗液中总蛋白含量、肺组织中髓过氧化物酶(MPO)活性等指标评价各组大鼠肺组织损伤情况，原位末端缺刻标记法(TUNEL)检测肺组织细胞凋亡情况，酶联免疫吸附测定(ELISA)检测肺组织中白细胞介素(IL)-6、IL-10及肿瘤坏死因子-α(TNF-α)的含量，蛋白质印迹法检测肺组织中活化胱天蛋白酶(cleaved-caspase)-3、cleaved-caspase-9、丝裂原细胞外信号调节激酶(MEK)、胞外信号调节激酶(ERK)的表达。结果HE染色显示，姜黄素低、中、高剂量组较假手术组仍有明显的病理改变，但较脓毒症组，肺组织损伤明显减轻，炎症细胞浸润现象明显较少；与脓毒症组相比，姜黄素低、中、高剂量组肺组织湿干比［(8.14±1.25)%、(6.82±1.19)%、(5.95±1.05)%比(9.73±1.36)%］、MPO 含量、细胞凋亡率［(16.27±2.14)%、(12.36±1.62)%、(8.59±1.26)%比(19.41±2.58)%］、cleaved-caspase-3、cleaved-caspase-9、IL-6、IL-10、TNF- α、磷酸化(p)-MEK/MEK(1.08±0.13、0.81±0.15、0.62±0.12比1.25±0.14)、p-ERK/ERK(1.16±0.14、0.97±0.13、0.75±0.11比1.34±0.15)及肺泡灌洗液中总蛋白量显著降低(P<0.05)，具有浓度依赖性。结论姜黄素可以保护脓毒症大鼠肺损伤，减少肺组织细胞的凋亡，减轻肺组织炎性水平，可能与下调MEK/ERK信号通路有关。 |
| 英文摘要: |
| Objective To analyze action mechanism of curcumin on relieving lung injury in sepsis rats.Methods The starting and ending time of this experiment was from August 2018 and April 2019, 75 male SD rats were assigned into 5 groups according to random number table method: sham operation group, sepsis group, low-dose, medium-dose and high-dose curcumin group, 15 cases in each group. The cecal ligation puncture was performed to construct sepsis rat models. In sham operation group, cecum was removed out by laparotomy and then returned in situ. The low-dose, medium-dose and high-dose curcumin group were intraperitoneally injected with 50, 100 and 200 mg/kg curcumin after surgery, respectively, while sham operation group and sepsis group were intraperitoneally injected withthe same amount of normal saline. The morphological changes of lung tissues were observed by hematoxylin-eosin (HE) staining.Lung wet-to-dry ratio, total protein content in bronchial lavage fluid and activity of myeloperoxidase (MPO) in lung tissue were applied to evaluate lung tissue injury in each group. The apoptosis of lung tissue was detected by TdT-mediated nick end labeling (TUNEL).The levels of interleukin (IL)-6, IL-10 and tumor necrosis factor-α (TNF-α) in lung tissues were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of cleaved cysteine proteinase 3 (cleaved-caspase-3), cleaved-caspase-9, mitogen-activated extracellular signal-regulated kinase (MEK) and extracellular regulated protein kinases (ERK) were detected by Western blotting.Results HE staining showed that there were significant pathological changes in low-dose, medium-dose and high-dose curcumin group comparedwith sham operation group. However, compared the sepsis group, lung tissue damage was significantly alleviated, and inflammatory cell infiltration was significantly less. Compared with sepsis group, lung tissue wet-to-dry ratio [(8.14±1.25)%, (6.82±1.19)%, (5.95±1.05)% vs. (9.73±1.36)%], MPO content, apoptosis index [(16.27±2.14)%, (12.36±1.62)%, (8.59±1.26)% vs. (19.41±2.58)%], cleavedcaspase-3, cleaved-caspase-9, IL-6, IL-10, TNF-α, phosphorylated (p)-MEK/MEK (1.08±0.13, 0.81±0.15, 0.62±0.12 vs. 1.25±0.14), p-ERK/ERK (1.16±0.14, 0.97±0.13, 0.75±0.11 vs. 1.34±0.15) and total protein content of bronchoalveolar lavage fluid in low-dose, medium-dose and high-dose curcumin group were significantly decreased (P<0.05), showing a concentration dependence.Conclusion Curcumin can protect lung injury in sepsis rats, reduce apoptosis of lung tissue cells, and alleviate inflammatory level of lung tissue, which may be related to down-regulation of MEK/ERK signaling pathway. |
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