摘要
目的:研究布地奈德联合辛伐他汀对慢性阻塞性肺疾病(COPD)大鼠并发动脉粥样硬化的影响及机制,为联合用药方案提供理论依据。方法:SD大鼠随机分为正常对照组、模型组(M组)、布地奈德组(BD组)、辛伐他汀组(SV组)和布地奈德+辛伐他汀组(BD+SV组)。以气管内滴注脂多糖和烟熏建立COPD并发动脉粥样硬化大鼠模型,采用吸入布地奈德(0.5 mg/kg,2次/d)和口服辛伐他汀(5 mg·kg-1·d-1)进行干预。实验60 d后,测定血清总胆固醇(TC)和高密度脂蛋白胆固醇(HDL-C)水平,计算动脉粥样硬化指数(AI),ELISA法测定各组大鼠血清C反应蛋白(CRP)、白细胞介素(IL)-6、IL-8、白三烯B4(LTB4)和肿瘤坏死因子-α(TNF-α)的水平,取肺和冠状动脉组织,经HE染色后检查病变情况,同时采用免疫组织化学方法检测肺组织基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶抑制剂-1(TIMP-1)的表达。结果:与正常对照组相比,其余4组大鼠的AI、血清炎性因子水平(CRP、IL-6、IL-8、LTB4和TNF-α)和肺组织MMP-9水平均明显升高(P均<0.05);与M组相比,BD组、SV组和BD+SV组大鼠上述指标均明显降低(P均<0.05);与BD组和SV组相比,BD+SV组仍有明显降低(P均<0.05)。各组TIMP-1水平比较结果与上述指标情况相反(P均<0.05)。与M组、BD组及SV组相比,BD+SV组大鼠肺组织中肺气肿形成的囊腔变小,各级支气管炎症减轻,冠状动脉内膜相对较平整,内膜增生及斑块形成程度明显降低。结论:布地奈德与辛伐他汀联合用药对COPD大鼠并发动脉粥样硬化有明显改善作用,其机制可能与降低动脉粥样硬化相关细胞因子水平、平衡基质金属蛋白酶与基质金属蛋白酶抑制剂的比例有关。
Objective:To study the effect and mechanism of treatment for atherosclerosis in COPD rats with combination of budesonide and simvastatin,and to provide the theoretical basis for the combination therapy.MethodsSD rats were randomly divided into normal control group,model group(M group)budesonide group(BD group),simvastatin group(SV group)and budesonide combined with simvastatin group(BD+SV group).Atherosclerosis in COPD rats model were established by administration of intratracheal drip and fumigation.Inhalation of budesonide(0.5 mg/kg,bid)and oral simvastatin(5 mg·kg 1·d 1)were used to treat rats with COPD complicated by atherosclerosis.Alter 60 days,serum total cholesterol(TC)and high density lipoprotein cholesterol(HDL-C)were measured to calculate,the atherosclerosis index(AI)serum CRP,IL-6,IL-8,LTB4 and TNF-a were measured by ELISA.The pathological changes of lung and coronary artery were examined alter HE stainning,and the expression of MMP-9 and TIMP-1 in lung tissue were detected by immunohistochemical method.Results:Compared with normal control groupthe AI and the levels of serum inflammatory factors including CRP,IL-6,IL-8,LTB4,TNF-a and MMP-9 in lung tissue of other 4 groups increased significantly.Compared with M group,the above indexes of BD group,SV group and BD+SV group were significantly decreased respectively.The above indexes of BD+SV group were stilldecreased significantly compared with BD group and SV group(all P<0.05).The changes of TIMP-1 levels were on the contrary.The cyst cavities formed by emphysema in lung tissue were reduced,the inflammation of all branches of bronchial trees was improvedthe coronary intima wasmore smooth and the degree of intimal hyperplasia and plaque formation was decreased significantly in the rats of BD+SV group compared with M group,BD group and SV group.Conclusions:The combination of budesonide and simvastatin can significantly inhibit the atherosclerosis associated with COPD.The mechanism may be related to the decrease of the level of atherosclerosis-related cytokines and the balance between matrix metalloproteinases and matrix metalloproteinases inhibitors in COPD rats.
作者
郭璐
杨凯
钟振东
GUO Lu;YANG Kai;ZHONG Zhendong(Department of Respiratory and Critical Care Medicine,Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital,Sichuan 610072;Department of Respiratory Medicine,The First Af filiated Hospital of Chengdu Medical College,Sichuan 610500;Institute for Laboratory Animal Research,Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital,Sichuan 610212,China)
出处
《国际心血管病杂志》
2018年第2期84-88,共5页
International Journal of Cardiovascular Disease
基金
四川省科技厅基础研究计划(2013JY0177)
