红花黄色素对慢性阻塞性肺疾病模型大鼠肺功能的改善作用

包海蓝 特日格乐 其木格

中圖分类号 R965 文献标志码 A 文章编号 1001-0408（2021）13-1578-05

DOI 10.6039/j.issn.1001-0408.2021.13.07

摘 要 目的：研究红花黄色素对慢性阻塞性肺疾病（COPD）模型大鼠肺功能的改善作用。方法：将SD大鼠随机分为对照组、模型组、阳性对照组（地塞米松，0.09 mg/kg）和红花黄色素低、中、高剂量组（5、10、20 mg/kg），对照组10只大鼠，其余组各11只大鼠。除对照组外，其余各组大鼠以注射脂多糖联合烟熏法复制COPD模型。造模成功后，对照组和模型组大鼠灌胃等体积生理盐水，给药组灌胃相应药物，每天1次，连续12周。末次给药后，采用酶联免疫吸附试验检测大鼠血清中肿瘤坏死因子α（TNF-α）、白细胞介素（IL-6）、IL-8水平;采用血气分析仪检测全血中血气指标[动脉氧分压（PaO2）、血氧饱和度（SaO2）、动脉二氧化碳分压（PaCO2）]水平;采用肺功能检测仪检测大鼠肺功能指标[肺活量（FVC）、1秒用力呼气量（FEV1）、FEV1/FVC、最大呼气量（PEF）、最大呼气时中期流速（MMEF）]水平;采用Western blot法检测大鼠肺组织中Toll样受体4（TLR4）、核因子κB（NF-κB）、NF-κB抑制蛋白（IκBα）表达水平;采用苏木精-伊红染色法观察大鼠肺组织的病理学形态变化。结果：与对照组比较，模型组大鼠血清中TNF-α、IL-6、IL-8水平，全血中PaCO2水平以及肺组织中TLR4、NF-κB蛋白表达水平均显著升高（P<0.01）;全血中PaO2、SaO2水平，肺功能指标FVC、FEV1、FEV1/FVC、PEF、MMEF水平以及肺组织中IκBα蛋白表达水平均显著降低（P<0.01）;肺组织上皮细胞出现明显的变性、坏死，细胞间质有明显的炎性浸润现象。与模型组比较，红花黄色素各剂量组大鼠血清中炎症因子水平、全血中血气指标水平、肺功能指标水平及肺组织中相关蛋白的表达水平（低剂量组的IκBα除外）均显著逆转（P<0.05或P<0.01）;肺组织上皮细胞坏死、脱落、炎性浸润等情况均不同程度地改善。结论：红花黄色素能明显改善COPD模型大鼠的肺功能;其作用机制可能与抑制炎症因子表达，调控TLR4/NF-κB通路相关蛋白的表达有关。

关键词 红花黄色素;慢性阻塞性肺疾病;炎症因子;Toll样受体4;核因子κB

Improvement Effects of Safflower Yellow on Lung Function of Chronic Obstructive Pulmonary Disease Model Rats

BAO Hailan1，Terigele2，Qimuge3（1. School of College of Mongolian Medicine， Inner Mongolia University for Nationalities， Inner Mongolia Tongliao 028000， China; 2. Network Center， Inner Mongolia University for Nationalities， Inner Mongolia Tongliao 028000， China; 3. Dept. of Mongolian Respiratory Medicine， the Affiliated Hospital of Inner Mongolia University for Nationalities， Inner Mongolia Tongliao 028000， China）

ABSTRACT   OBJECTIVE： To study the improvement effects of safflower yellow on lung function in chronic obstructive pulmonary disease （COPD） model rats. METHODS： SD rats were randomly divided into control group， model group， positive control group （dexamethasone， 0.09 mg/kg）， safflower yellow low-dose， medium-dose and high-dose groups （5， 10， 20 mg/kg）， with 10 rats in control group and 11 rats in other groups. Except for control group， other groups were given lipopolysaccharide combined with fumigation to induce COPD model. After modeling， control group and model group were given constant volume of normal saline intragastrically， and administration groups were given relevant medicine intragastrically， once a day， for consecutive 12 weeks. After last medication， the levels of TNF-α， IL-6 and IL-8 were detected by ELISA. The levels of blood gas indexes （PaO2， SaO2 and PaCO2） in whole blood were detected by blood gas analyzer. The levels of lung function indexes （FVC， FEV1， FEV1/FVC， PEF and MMEF） were detected by lung function analyzer. The expression of TLR4， NF-κB and IκB-α protein were detected by Western blot. HE staining was used to observe the pathological changes of lung tissue. RESULTS： Compared with control group， the serum levels of TNF-α， IL-6 and IL-8， the level of PaCO2 in whole blood as well as the protein expression of TLR4 and NF-κB in lung tissue were increased significantly in model group （P<0.01）; the levels of PaO2 and SaO2 in whole blood， the levels of lung function as FVC， FEV1， FEV1/FVC， PEF and MMEF as well as the protein expression of     IκBα in lung tissue were decreased significantly （P<0.01）; there were obvious degeneration and necrosis in the epithelial cells of lung tissue， and obvious inflammatory infiltration in the interstitial cells. Compared with model group， the levels of inflammatory factors in serum， blood gas indexes in whole blood and lung function indexes as well as the expression of related protein in lung tissue （except for IκBα in low-dose group） were reversed significantly in safflower yellow groups （P<0.05 or P<0.01）; the necrosis， exfoliation and inflammatory infiltration of epithelial cells in lung tissue were improved in varying degrees. CONCLUSIONS： Safflower yellow can significantly improve the lung function of COPD model rats， and its mechanism may be related to inhibiting the expression of inflammatory factors and regulating the expression of TLR4/NF-κB pathway-related proteins.

KEYWORDS   Safflower yellow; Chronic obstructive pulmonary disease; Inflammatory factors; TLR4; NF-κB

慢性阻塞性肺疾病（COPD）是一种具有气流阻塞特征的慢性支气管炎和（或）肺气肿，主要表现为进行性的肺功能衰退及慢性炎症反应[1-3]，且随着其病程发展可能会导致动脉粥样硬化、静脉栓塞等多种并发症[4-6]，极大程度地损害了患者的生命安全。因此，寻找能够有效治疗、改善COPD的用药方案具有重要的临床意义。……