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目的探讨辛伐他汀早期干预对慢性阻塞性肺疾病(慢阻肺)大鼠肺部及系统性炎症反应的影响。方法将40只雄性Wistar大鼠随机均分为正常组(A组)、辛伐他汀组(B组)、慢阻肺模型组(C组)、辛伐他汀干预组(D组),每组10只。C组和D组采用反复香烟烟雾暴露法制备慢阻肺模型。B组和D组大鼠采用辛伐他汀5 mg·kg~(-1)·d~(-1)灌胃,其他两组用等体积的生理盐水灌胃,共16周。造模结束后留取血液标本测定系统性炎症指标[外周血白细胞计数(WBC)及血清超敏C反应蛋白(hs-CRP)];制作肺组织病理切片进行病理学观察,计数平均肺内衬间隔(MLI)和平均肺泡数(MAN)。结果 C组与D组的气道炎症病理评分、MLI、外周血WBC及血清hs-CRP水平均较A、B组明显增高(P均<0.01),MAN则较A、B组明显减低(P均<0.01)。与C组比较,D组气道炎症病理评分、MLI、外周血WBC及血清hs-CRP均明显减低(P均<0.01),MAN较C组增高(P<0.01)。外周血WBC、血清hs-CRP水平与气道内炎症病理评分成正相关(r=0.598,P<0.01;r=0.767,P<0.01),与MAN则成负相关(r=-0.657,P<0.01;r=-0.702,P<0.01)。结论辛伐他汀可抑制肺部及系统性炎症反应,减轻肺气肿的程度,从而有可能延缓肺功能的下降。
Objective To investigate the effects of simvastatin on lung and systemic inflammatory response in chronic obstructive pulmonary disease (COPD) rats. Methods Forty male Wistar rats were randomly divided into normal group (group A), simvastatin group (group B), COPD group (group C) and simvastatin intervention group (group D) 10 only C group and D group were prepared by repeated cigarette smoke exposure COPD model. Rats in groups B and D were given intragastric administration of simvastatin 5 mg · kg -1 · d -1, and the other two groups were given intragastrically with equal volume of saline for 16 weeks. Blood samples were collected after modeling to determine systemic inflammatory markers (WBC and hs-CRP); pathological sections of lung were made for pathological observation, and the mean lung lining Interval (MLI) and mean alveolar number (MAN). Results The levels of inflammatory pathology, MLI, WBC and hs-CRP in group C and group D were significantly higher than those in group A and B (all P <0.01), and were significantly lower in group A and B than in group A and B All <0.01). Compared with group C, the pathological score of airway inflammation, MLI, WBC and serum hs-CRP in group D were significantly decreased (all P <0.01), MAN increased compared with group C (P <0.01). The levels of WBC and serum hs-CRP in peripheral blood were positively correlated with pathological scores of airway inflammation (r = 0.598, P <0.01; r = 0.767, P <0.01) ; r = -0.702, P <0.01). Conclusion Simvastatin can inhibit the pulmonary and systemic inflammatory response, reduce the degree of emphysema, which may delay the decline in lung function.