摘要
目的探究阿托伐他汀对烟熏慢性阻塞性肺病(COPD)大鼠肺组织内质网应激和炎症的影响。方法将60只清洁级Wistar雄性大鼠随机分成模型组、正常对照组、阿托伐他汀低剂量组、阿托伐他汀高剂量组,每组15只。采用被动吸烟加气管内滴注脂多糖法建立大鼠COPD模型。阿托伐他汀低剂量组和阿托伐他汀高剂量组分别腹腔注射1 ml·kg^(-1)·d^(-1)和2 ml·kg^(-1)·d^(-1)阿托伐他汀溶液。正常对照组和模型组大鼠给予腹腔注射2 ml的0.9%氯化钠溶液。利用TUNEL法检测各组大鼠细胞凋亡情况;采用免疫组化检测GADD153和GRP78蛋白表达水平;收集各组大鼠肺组织、血清进行病理学观察及炎性因子测定。结果与模型组比较,阿托伐他汀低剂量组与高剂量组肺组织上皮细胞凋亡指数均显著降低,GRP78蛋白表达增加,GADD153蛋白表达降低,且差异有统计学意义(P<0.05)。与模型组比较,阿托伐他汀低剂量组和阿托伐他汀高剂量组血清和肺泡灌洗液炎性因子肿瘤坏死因子-α(TNF-α)、白介素1β(IL-1β)、IL-6、IL-8均有所下降,差异有统计学意义(P<0.05),且呈剂量依赖性。结论阿托伐他汀不仅能减轻烟熏COPD大鼠内质网应激,诱导的肺泡上皮细胞凋亡,而且能减少COPD大鼠肺组织炎性反应,抑制炎性因子释放。
Objective To explore the effects of atorvastatin on endoplasmic reticulum stress and inflammation in lung tissues of rats with COPD induced by smoking. Methods Sixty clean male Wistar rats were randomly divided into model group ( n =15), normal control group ( n =15), low-dose atorvastatin group ( n =15) and high-dose atorvastatin group ( n =15). COPD models were established by passive smoking and intratracheal instillation of lipopolysaccharide. The rats in low-dose atorvastatin group and high-dose atorvastatin group were intraperitoneally injected with 1ml·kg ^-1 ·d ^-1 and 2ml·kg^-1 ·d^-1 of atorvastatin solution, respectively. The rats in model group and normal control group were injected with2 ml of 0.9% normal saline. Moreover, TUNEL and immunohistochemistry were used to detect the apoptosis of rats in each group and the expression of the levels of GADD153 and GRP78 protein, respectively. In addition, the lung tissues and serum of the rats in each group were collected for pathological observation and inflammatory factors measurement. Results As compared with those in model group, the apoptotic indexes of pulmonary epithelial cells in low-dose and high-dose atorvastatin group were significantly decreased. And the expression levels of GRP78 protein were significantly increased, however, the expression levels of GADD153 protein were significantly decreased ( P <0.05). And the inflammatory factors TNF-α,IL1-β,IL-6, IL-8 in serum and alveolar lavage in low-dose and high-dose atorvastatin group were significantly decreased in a dose-dependent manner ( P < 0.05 ). Conclusion Atorvastatin can not only reduce endoplasmic reticulum stress in rats with COPD due to smoking, induce apoptosis of alveolar epithelial cells, but also can reduce the inflammatory response in lung tissues of rats and inhibit the release of inflammatory factors.
作者
王戈
WANG GE(Department of Internal Medicine,TCM Hospital of Xishui County,Hubei,Xishui 438200,China)
出处
《河北医药》
CAS
2019年第10期1502-1505,共4页
Hebei Medical Journal
关键词
阿托伐他汀
慢性阻塞性肺病
大鼠
肺组织内质网应激
肺组织炎症
atorvastatin
chronic obstructive pulmonary disease
rats
endoplasmic reticulum stress in lung tissues
lung tissues inflammation
