| 引用本文: |
刘敏,王启芝,刘雨,柏正平.复方葶苈子汤改善COPD相关性肺动脉高压大鼠的肺血管重塑的机制研究[J].湖南中医药大学学报,2022,42(3):380-386[点击复制] |
|
| |
|
|
| 本文已被：浏览 1489次 下载 474次 |
| 复方葶苈子汤改善COPD相关性肺动脉高压大鼠的肺血管重塑的机制研究 |
| 刘敏,王启芝,刘雨,柏正平 |
| (湖南中医药大学, 湖南 长沙 410208;湖南省中医药研究院附属医院, 湖南 长沙 410006;湖南中医药大学, 湖南 长沙 410208;湖南省中医药研究院, 湖南 长沙 410006) |
| 摘要: |
| 目的 探讨复方葶苈子汤对慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）相关性肺动脉高压（pulmonary arterial hypertension, PAH）大鼠肺血管重塑的影响及机制。方法 将90只SD大鼠随机分为正常组、模型组、低剂量组、中剂量组、高剂量组和西药组。正常组大鼠正常喂养，其余组大鼠均采用烟熏加气管滴注脂多糖构建COPD-PAH大鼠模型。低剂量组、中剂量组、高剂量组予复方葶苈子汤（生药量分别为2.56、5.13、10.26 g/kg），西药组予辛伐他汀2.5 mg/kg，模型组予以等量0.9％生理盐水，给与相应药液（10 mL/kg），在实验第60天开始，每天灌胃1次，连续14 d。HE染色观察肺组织病理变化，Masson染色观察肺小动脉胶原沉积，免疫组化观察肺组织增殖指标增殖细胞核抗原（proliferating cell nuclear antigen, PCNA）的变化，Western blot检测细胞焦亡通路NLRP3、Caspase-1、GSDMD、IL-1β、IL-18的蛋白水平。结果 与正常组相比，模型组出现典型的COPD-PAH病理变化，肺小动脉胶原沉积面积、PCNA表达及肺组织中NLRP3、Caspase-1、GSDMD、IL-1β、IL-18蛋白水平均增加（P<0.05）；与模型组相比，中剂量组、高剂量组和西药组肺组织病理变化明显改善，肺小动脉胶原沉积面积、PCNA表达及肺组织中NLRP3、Caspase-1、GSDMD、IL-1β、IL-18蛋白水平均减少（P<0.05）；与低剂量组相比，中剂量组、高剂量组和西药组肺组织病理变化明显改善，肺小动脉胶原沉积面积、PCNA表达均及肺组织中NLRP3、Caspase-1、GSDMD、IL-1β、IL-18蛋白水平均减少（P<0.05）；与中剂量组相比，高剂量组肺组织病理变化明显改善，肺小动脉胶原沉积面积、PCNA表达及肺组织中NLRP3、Caspase-1、GSDMD、IL-1β、IL-18蛋白水平均减少（P<0.05）。结论 复方葶苈子汤可通过抑制NLRP3炎症小体介导的细胞焦亡，改善COPD-PAH大鼠的肺血管重塑，且随着复方葶苈子汤剂量的增加，COPD-PAH大鼠的肺血管重塑改善效果越明显。 |
| 关键词: 复方葶苈子汤 NLRP3 细胞焦亡 肺血管重塑 慢性阻塞性肺疾病相关性肺动脉高压 |
| DOI：10.3969/j.issn.1674-070X.2022.03.006 |
| 投稿时间：2021-06-21 |
| 基金项目:国家自然科学基金面上项目（81874459）；湖南省技术创新引导计划（临床医疗技术创新引导项目）（2017SK50407）；2020年湖南中医药大学研究生创新课题（2020CX08）；湖南省中医药管理局一般指导项目（E2022018）。 |
|
| Mechanism of Compound Tinglizi Decoction in improving pulmonary vascular remodeling in COPD-related pulmonary arterial hypertension rats |
| LIU Min,WANG Qizhi,LIU Yu,BAI Zhengping |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208. China;The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, Hunan 410006, China;Hunan University of Chinese Medicine, Changsha, Hunan 410208. China;Hunan Academy of Chinese Medicine, Changsha, Hunan 410006, China) |
| Abstract: |
| Objective To investigate the effects and mechanisms of Compound Tinglizi Decoction on pulmonary vascular remodeling in rats with chronic obstructive pulmonary disease (COPD)-pulmonary arterial hypertension (PAH）. Methods Ninety SD rats were randomly divided into normal group, model group, low-dose group, middle-dose group, high-dose group and western medicine group. The rats in the normal group were fed normally, and the rats in the other groups were all used to construct the COPD-PAH rat model by smoke plus tracheal drip of lipopolysaccharide. The low-dose group, middle-dose group, and high-dose group were given Compound Tinglizi Decoction (the crude drug doses were 2.56, 5.13, and 10.26 g/kg, respectively), the western medicine group was given simvastatin 2.5 mg/kg, and the model group was given the same amount of 0.9% physiological saline administered, with the corresponding drug solution (10 mL/kg), and from the 60th day of the experiment, the rats were given intragastrical once a day for 14 consecutive days. Histopathological changes in the lungs of rats in each group were observed by HE staining. Collagen deposition in small pulmonary arteries was observed by Masson staining. Changes in proliferation indicators proliferating cell nuclear antigen (PCNA) in lung tissue were observed by immunohistochemistry. Protein levels of NLRP3, Caspase-1, GSDMD, IL-1β, IL-18 in pyroapoptotic pathways were measured by Western blot. Results Compared with the normal group, the model group had typical pathological changes of COPD-PAH, and the collagen deposition area of pulmonary arterioles, the expression of PCNA and the protein levels of NLRP3, Caspase-1, GSDMD, IL-1β and IL-18 in the lung tissue were increased (P<0.05). Compared with the model group, the pathological changes of lung tissue in the middle-dose group, high-dose group and western medicine group were significantly improved, the collagen deposition area of pulmonary arterioles, the expression of PCNA, and the protein levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in lung tissue were reduced (P<0.05). Compared with the low-dose group, the pathological changes of lung tissue in the middle-dose group, high-dose group and western medicine group were significantly improved, the collagen deposition area of pulmonary arterioles, the expression of PCNA and the protein levels of NLRP3, Caspase-1, GSDMD, IL-1β, IL-18 were reduced (P<0.05). Compared with the middle-dose group, the pathological changes of lung tissue in the high-dose group were significantly improved, and the collagen deposition area of pulmonary arterioles, the expression of PCNA and the protein levels of NLRP3, Caspase-1, GSDMD, IL-1β and IL-18 in the lung tissue were all decreased (P<0.05). Conclusion Compound Tinglizi Decoction can improve pulmonary vascular remodeling in rats with COPD-PAH through inhibiting NLRP3 inflammatory vesicle-mediated pyroptosis, and with the increase of the dose of Compound Tinglizi Decoction, the improvement effect of pulmonary vascular remodeling in COPD-PAH rats is more obvious. |
| Key words: Compound Tinglizi Decoction NLRP3 pyroptosis pulmonary vascular remodeling chronic obstructive pulmonary disease-associated pulmonary hypertension |
|
二维码（扫一下试试看！） |
|
|
|
|
