中国组织工程研究

中国组织工程研究 ›› 2021, Vol. 25 ›› Issue (2): 274-280.doi: 10.3969/j.issn.2095-4344.2952

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

麻杏芎葶合剂干预肺心病急性发作模型小鼠肺组织重构和肺血管重塑相关因子的表达

李松桃，李欣奕，宋云峰，宁加银，任  强，杨仁旭，彭  波   

  1. 成都中医药大学附属医院/临床医学院，四川省成都市   610075
  • 收稿日期:2020-01-09 修回日期:2020-01-14 接受日期:2020-03-07 出版日期:2021-01-18 发布日期:2020-11-21
  • 通讯作者: 彭波，博士，副教授，成都中医药大学附属医院/临床医学院，四川省成都市 610075
  • 作者简介:李松桃，男，1996年生，四川省绵竹市人，汉族，成都中医药大学七年制中西医临床医学专业在读，主要从事中西医防治内科疾病研究。
  • 基金资助:
    四川省科技厅苗子工程(2018RZ0126)；成都中医药大学“杏林学者”学科人才科研提升计划(QNXZ2019042)；成都中医药大学附属医院院基金(18PY15)

Maxing Xiongting Mixture regulates factors relevant to lung reshaping and vascular remodeling of hypoxic pulmonary hypertension rats

Li Songtao, Li Xinyi, Song Yunfeng, Ning Jiayin, Ren Qiang, Yang Renxu, Peng Bo   

  1. Affiliated Hospital / Clinical Medical College of Chengdu University of Traditional Chinese Medicine, Chengdu  610075, Sichuan Province, China
  • Received:2020-01-09 Revised:2020-01-14 Accepted:2020-03-07 Online:2021-01-18 Published:2020-11-21
  • Contact: Peng Bo, MD, Associate professor, Affiliated Hospital / Clinical Medical College of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
  • About author:Li Songtao, Affiliated Hospital / Clinical Medical College of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
  • Supported by:
    the Seed Engineering Plan of Sichuan Provincial Science and Technology Department, No. 2018RZ0126; “Xinglin Scholar” Discipline Talent Culture Program of Chengdu University of Traditional Chinese Medicine, No. QNXZ2019042; the Fund of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, No. 18PY15

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摘要：

文题释义：
麻杏芎葶合剂：为四川省名老中医杨仁旭主任医师40多年临证经验总结，依据《伤寒论》中“葶苈大枣泻肺汤”结合《太平惠民和剂局方》中“麻杏汤”加减化裁，由麻黄、川芎、葶苈子、杏仁四药组成，针对低氧性肺动脉高压的基本病机：痰瘀互结、肺失宣降，具有良好的临床效果。
低氧性肺动脉高压：由缺氧引起的以肺血管结构重建与肺动脉压升高为特征的疾病，主要病理表现为肺动脉内皮细胞功能紊乱、中膜平滑肌细胞增殖和细胞外基质沉积，使得肺动脉血管壁病理性增厚，肺动脉血管压力上升，最终致使右心室肥厚，是慢性阻塞性肺疾病向肺心病发展的关键环节。

背景：低氧性肺动脉高压是慢性阻塞性肺疾病向肺心病发展的关键环节，其严重程度与疾病发展及预后密切相关，目前的治疗不能预防或逆转疾病进展，而在临床应用麻杏芎葶合剂对痰瘀互结型低氧性肺动脉高压疗效显著。
目的：探究麻杏芎葶合剂对痰瘀互结型低氧性肺动脉高压大鼠肺组织重构和肺血管重塑相关因子的调节作用。
方法：将70只5周龄SD大鼠随机分为空白对照组10只，其余60只大鼠诱发建立大鼠肺心病急性发作期动物模型(1%野百合碱溶液50 mg/kg腹腔注射)后，先后将大鼠置于烟熏箱模拟吸烟环境、强迫游泳装置建立大鼠痰瘀互结模型，每周6 d，连续4周。造模结束后，剩余46只大鼠根据体质量正态分布情况，挑选40只随机分为模型组10只，麻杏芎葶高剂量组10只，麻杏芎葶低剂量组10只，阳性药物法舒地尔组10只。麻杏芎葶合剂高剂量、低剂量组分别予以麻杏芎葶合剂20，5 g/(kg·d)，法舒地尔组予以法舒地尔10 mg/(kg·d)，空白对照组和模型组用等量生理盐水，均采用灌胃、腹腔注射联合给药，每天1次，连续14 d。采用RT-PCR检测肺组织重构和肺血管重塑相关因子RhoA 、间质溶素1及肿瘤坏死因子α mRNA表达。实验方案经成都中医药大学伦理委员会批准(伦理编号：2017-03)。
结果与结论：①与模型组相比，麻杏芎葶高剂量组RhoA、间质溶素1及肿瘤坏死因子α的基因表达均降低(均P < 0.05)，法舒地尔组RhoA及肿瘤坏死因子α基因表达降低(均P < 0.05)，间质溶素1基因表达明显降低(P < 0.01)，麻杏芎葶低剂量组RhoA、间质溶素1及肿瘤坏死因子α基因表达差异均无显著性意义；麻杏芎葶高剂量组与法舒地尔组RhoA、间质溶素1及肿瘤坏死因子α的基因表达差异无显著性意义(P > 0.05)；②结果说明，麻杏芎葶合剂可通过抑制RhoA、间质溶素1、肿瘤坏死因子α的mRNA表达干预痰瘀互结型低氧性肺动脉高压大鼠模型的肺组织重构和肺血管重塑，与法舒地尔效果相似。
https//orcid.org/0000-0002-6297-5351(李松桃) 

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 麻杏芎葶合剂, 低氧性肺动脉高压, RhoA, 肿瘤坏死因子α, 间质溶素1, 肺组织重构, 肺血管重塑

Abstract: BACKGROUND: Hypoxic pulmonary hypertension is a key link in the progression from chronic obstructive pulmonary disease to cor pulmonale. Its severity is closely related to disease development and prognosis. Current treatments cannot prevent or reverse disease progression. Maxing Xiongting Mixture has significant effect on hypoxic pulmonary hypertension with the syndrome of intermingled phlegm and blood stasis.
OBJECTIVE: To study how the Maxing Xiongting Mixture regulates relevant factors of lung reshaping and vascular remodeling of hypoxic pulmonary hypertension rats with the syndrome of intermingled phlegm and blood stasis. 
METHODS: Seventy Sprague-Dawley rats, 5 weeks old, were randomly divided into normal group (n=10) and model group (n=60), where acute cor pulmonale model was prepared by injecting 50 mg/kg monocrotaline solution (1%) intraperitoneally, followed by forced smoking and swimming 6 days a week lasting for 4 weeks. Except for 10 rats in the normal group, there were 46 model rats in the model group. According to the normal distribution of body mass, 40 rats were selected and randomly divided into 4 groups: model group, high-dose Maxing Xiongting Mixture group (MH), low-dose Maxing Xiongting Mixture group (ML) and fasudil group, with 10 rats in each group. Rats in MH and ML groups were respectively given Maxing Xiongting Mixture at 20 g/(kg·d) and 5 g/(kg·d), respectively and those in the fasudil group were given fasudil at a dose of 10 mg/(kg·d). Other groups were given equal amount of saline. Administration was given intraperitoneally and intragastrically, once a day for 14 days in total. RT-PCR was used to test the expression of factors related to lung reshaping and vascular remodeling, including RhoA, stromelysin 1 and tumor necrosis factor-α mRNAs. An approval for the study was obtained from the Ethics Committee of Chengdu University of Traditional Chinese Medicine (approval No. 2017-03).
RESULTS AND CONCLUSION: Compared with the model group, the expressions of RhoA, stromelysin 1, and tumor necrosis factor-α mRNAs were significantly lowered in the MH group (all P < 0.05); the mRNA expressions of RhoA (P < 0.05), stromelysin 1 (P < 0.01) and tumor necrosis factor-α (P < 0.05) were significantly reduced in the fasudil group; and no significant changes in the above expressions of relevant factors were found in the ML group (P > 0.05). To conclude, Maxing Xiongting Mixture, which is similar to fasudil, intervenes lung reshaping and vascular remodeling of hypoxic pulmonary hypertension rats with the syndrome of intermingled phlegm and blood stasis by inhibiting the expressions of RhoA, stromelysin 1, and tumor necrosis factor-α mRNAs. 

Key words: Maxing Xiongting Mixture, hypoxic pulmonary hypertension, RhoA, tumor necrosis factor-α,  , stromelysin 1, lung reshaping, vascular remodeling

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