| 秦玉春,邝向东,蔡林再,等.水蛭素抑制 RhoA/Rho激酶信号通路对慢性阻塞性肺疾病大鼠炎症反应和纤维化的影响[J].安徽医药,2022,26(12):2350-2354. |
| 水蛭素抑制 RhoA/Rho激酶信号通路对慢性阻塞性肺疾病大鼠炎症反应和纤维化的影响 |
| Influence of hirudin on inflammatory response and fibrosis in rats with chronic obstructive pulmonary disease by inhibiting RhoA/Rho kinase signaling pathway |
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| DOI：10.3969/j.issn.1009-6469.2022.12.004 |
| 中文关键词: 水蛭素类 肺疾病，慢性阻塞性 峰值呼气流速 白细胞介素 1β 肿瘤坏死因子 α 纤维化 RhoA/ROCK信号通路 大鼠， Sprague-Dawley 蛭素 |
| 英文关键词: Hirudins Pulmonary disease, chronic obstructive Peak expiratory flow rate Interleukin-1beta Tumor necrosis factor-alpha Fibrosis RhoA/ROCK signaling pathway Rats, Sprague-Dawley |
| 基金项目:海南省卫生健康行业科研项目( 20A200304) |
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| 中文摘要: |
| 目的探讨水蛭素抑制 RhoA/Rho激酶(ROCK)信号通路对慢性阻塞性肺疾病(COPD)大鼠炎症反应和纤维化的影响。方法 2020年 1—6月，将 52只清洁级 SD大鼠随机数字表法分为造模组( 42只)和对照组( 10只)。造模组大鼠通过气管内滴注脂多糖( LPS)溶液建立 COPD模型，建模后的大鼠随机数字表法分为模型组、水蛭素组( 50 U/kg)、 ROCK激活剂组［溶血磷脂酸( LPA，40 μg/kg)组、水蛭素 +LPA组( 50 U/kg水蛭素 +40 μg/kg LPA)］，10只/组。药物组和激活剂组分别按照相应剂量进行干预；其余各组给予生理盐水干预。干预结束后，检测各组大鼠肺功能指标 -呼气峰值流速( PEF)及 0.3秒用力呼气容积(FEV0.3)、用力肺活量比值( FVC)；颈总动脉取血，检测血清中炎性因子指标［白细胞介素 -1β(IL-1β)、肿瘤坏死因子 -α(TNF-α)］水平；分离肺组织，观察肺组织形态学变化、肺纤维化程度以及 RhoA/ROCK信号通路蛋白表达情况。结果对照组大鼠无肺组织损伤；与对照组 PEF(11.21±1.12)V/mL，FEV0.3(31.68±3.24)mL/s，FVC(8.56±0.85)V/mL，IL-1β(65.78±6.66)ng/L，TNF-α(100.32±10.02)ng/L相比，模型组大鼠肺组织损伤及纤维化较为严重， PEF(7.41±0.71)V/mL、FEV0.3(22.42±2.21)mL/s、FVC(4.61±0.46)V/mL较显著降低( P<0.05)，而 IL-1β(158.63±15.89)ng/L、TNF-α(545.37±54.56)ng/L显著增加， RhoA、Rho激酶 1(ROCK1)蛋白表达也增加( P<0.05)；与模型组相比，经水蛭素组大鼠肺组织损伤及纤维化程度得到改善， PEF(5.34±0.53)V/mL、FEV0.3(16.15±1.62)mL/s、FVC(8.21±0.82)V/mL较模型组显著增加( P<0.05)而 IL-1β(68.72±6.88)ng/L、TNF-α(115.35±11.55)ng/L显著降低， RhoA、ROCK1蛋白表达均显著降低(P<0.05)； LPA可减弱水对 COPD大鼠炎症反应和肺纤维化的改善作用(P<0.05)。结论水蛭素可以降低炎症细胞浸润，改善肺组织损伤和肺纤维化，可能与抑制 RhoA/ROCK信号通路有关。 |
| 英文摘要: |
| Objective To investigate the influences of hirudin on inflammation and fibrosis in rats with chronic obstructive pulmo.nary disease (COPD) by inhibiting RhoA/Rho kinase (ROCK) signaling pathway.Methods The experimental study started and ended from January to June 2020. Fifty-two rats were grouped into model group (42 rats) and control group (10 rats) by random number tablemethod. The rats in the model group were treated by intratracheal instillation of lipopolysaccharide (LPS) solution to establish a COPDmodel, and after modeling, the rats were separated into model group, hirudin group (50 U/kg), ROCK activator [lysophosphatidic acid(LPA), 40 μg/kg], hirudin + LPA group (50 U/kg hirudin + 40 μg/kg LPA), with 10 animals/group by random number table method. Thedrug group and the activator group were intervened according to the corresponding doses; the other groups were intervened with normalsaline. After intervention, the pulmonary function indexes of rats in each group were detected, infcluding peak expiratory flow rate(PEF), forced expiratory volume in 0.3 seconds (FEV0.3), and forced vital capacity ratio (FVC); blood was collected from the commoncarotid artery to detect the levels of inflammatory cytokines-interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum; lungtissue was isolated to observe the morphological changes of lung tissue, the degree of pulmonary fibrosis and the expression of RhoA/ROCK signaling pathway proteins.Results There was no lung tissue damage in the control group; Compared with the control groupPEF (11.21±1.12) V/mL, FEV0.3 (31.68±3.24) mL/s, FVC (8.56±0.85) V/mL, IL-1β (65.78±6.66) ng/L, TNF-α (100.32±10.02) ng/L,In the model group, PEF (7.41±0.71) V/mL, FEV0.3 (22.42±2.21) mL/s and FVC (4.61±0.46) V/mL were significantly lower than those in the model group (P<0.05), while IL-1β (158.63±15.89) ng/L and TNF-α (545.37±54.56) ng/L were significantly increased, and the protein expressions of RhoA and ROCK1 were also increased (P<0.05); Compared with the model group, the degree of lung tissue inju.ry and fibrosis were improved in the hirudin group, PEF (5.34±0.53) V/mL, FEV0.3 (16.15±1.62) mL/s, FVC (8.21±0.82) V/mL weresignificantly increased compared with the model group (P<0.05), while IL-1β (68.72±6.88) ng/L and TNF-α (115.35±11.55) ng/L were significantly decreased, and the protein expression of RhoA and ROCK1 were significantly decreased (P<0.05). LPA was able to attenu. ate the improvement effects of hirudin on inflammation and pulmonary fibrosis in COPD rats (P<0.05).Conclusion Hirudin can re. duce inflammatory cell infiltration, improve lung tissue damage and pulmonary fibrosis, which may be related to the inhibition of RhoA/ROCK signaling pathway. |
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