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

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

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αmRNA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。

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-αmRNAs.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-αmRNAs 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-αmRNAs.