摘要
目的探索阿托伐他汀联合环孢素A对百草枯中毒大鼠肺纤维化的疗效。方法Wistar大鼠50只随机分为5组,每组10只。对照(Control)组给予生理盐水1 mL灌胃,其余4组单次给予单剂量百草枯20 mg/kg灌胃以染毒。然后,模型(PQ)组以生理盐水1 mL灌胃;阿托伐他汀(PQ+STN)组、环孢素A(PQ+CsA)组以及联合用药(PQ+STN+CsA)组分别以阿托伐他汀20 mg/kg、环孢素A 10 mg/kg以及阿托伐他汀20 mg/kg+环孢素A 10 mg/kg灌胃,每天1次,共7 d。HE和Masson s染色观察肺组织病理学变化;测定肺湿重/干重比、羟脯氨酸含量;酶联免疫吸附实验(ELISA)检测肺组织TNF-0x0E䥺SymbolaA@0x0F、IL-10x0E䥺SymbolbA@0x0F、IL-6含量;Western blot检测TGF-0x0E䥺SymbolbA@0x0F、CollagenⅠ、CollagenⅢ、MMP-2、MMP-9、E-cadherin、Vimentin和0x0E䥺SymbolaA@0x0F-SMA的蛋白表达;试剂盒检测超氧化物歧化酶(SOD)、丙二醛(MDA)、还原型谷胱甘肽(GSH)等指标。结果HE染色结果显示,与Control组比较,PQ组肺泡壁变厚、免疫细胞聚集、肺泡破裂;Masson s染色显示肺组织明显纤维化。与PQ组比较,PQ+STN组和PQ+CsA组均一定程度减轻肺损伤和纤维化,PQ+STN+CsA组对肺损伤和纤维化的改善最明显。与Control组比较,PQ组肺湿重/干重比升高(P<0.05),肺羟脯氨酸含量增加(P<0.01),TNF-α、IL-1β和IL-6升高(P<0.01),MDA增加(P<0.01),SOD和GSH降低(P<0.01),纤维化标志蛋白TGF-β、CollagenⅠ和CollagenⅢ升高(P<0.01),MMP-2、MMP-9、Vimentin和α-SMA升高(P<0.01),E-cadherin降低(P<0.01)。与PQ组比较,PQ+STN组、PQ+CsA组和PQ+STN+CsA组肺湿重/干重比、肺羟脯氨酸含量、TNF-α、IL-1β、IL-6、MDA、TGF-β、CollagenⅠ、CollagenⅢ、MMP-2、MMP-9、Vimentin和α-SMA降低(P<0.05),SOD、GSH和E-cadherin升高(P<0.05)。结论阿托伐他汀联合环孢素A能更有效减轻百草枯中毒导致的肺纤维化,控制氧化应激和炎症,其机制可能与其对细胞移动能力相关蛋白的调控有关。
Objective To investigate the curative effect of atorvastatin combined with cyclosporine A on pulmonary fibrosis in paraquat poisoned rats.Methods A total of 50 Wistar rats were randomly divided into 5 groups,with 10 rats in each group.The Control group was intragastrically administered with 1 mL of normal saline,and the other 4 groups were intragastrically administered with a single dose of paraquat 20 mg/kg for poisoning.Then,the model(PQ)group was intragastrically administered with 1 mL of normal saline.The atorvastatin(PQ+STN)group,the cyclosporine A(PQ+CsA)group and the combined medication(PQ+STN+CsA)group were respectively intragastrically administered with atorvastatin 20 mg/kg,cyclosporine A 10 mg/kg and atorvastatin 20 mg/kg+cyclosporine A 10 mg/kg,once a day for a total of 7 days.HE and Masson’s staining were used to observe the pathological changes of lung tissues.The wet weight/dry weight ratio of lung and hydroxyproline content were measured.The enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of TNF-α,IL-1βand IL-6 of lung tissues.Western blot was used to detect the protein expressions of TGF-β,CollagenⅠ,CollagenⅢ,MMP-2,MMP-9,E-cadherin,Vimentin andα-SMA.The kit was used to detect the indicators of superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione(GSH).Results The results of HE staining showed that compared with the Control group,the alveolar wall of the PQ group became thicker,with the accumulation of immune cells and alveolar rupture.Masson’s staining showed obvious fibrosis of lung tissues.Compared with the PQ group,the PQ+STN group and the PQ+CsA group both alleviated the lung injury and fibrosis to a certain extent,and the PQ+STN+CsA group showed the most obvious improvement on the lung injury and fibrosis.Compared with the Control group,the wet weight/dry weight ratio of lung in the PQ group was increased(P<0.05),the lung hydroxyproline content was increased(P<0.01),the TNF-α,IL-1βand IL-6 were increased(P<0.01),the MDA was increased(P<0.01),the
作者
时洁
刘伟
周莲
刘卫红
耿晓康
SHI Jie;LIU Wei;ZHOU Lian;LIU Wei-hong;GENG Xiao-kang(Department of Pharmacy,Ministry of Western Medicine,Central Hospital of Enshi Tujia and Miao Autonomous Prefecture,Enshi Hubei 445000,China;Department of Radiology,China Resources WISCO General Hospital,Wuhan Hubei 430080,China;Department of Pharmacy,Women and Children’s Hospital of Enshi Central Hospital,Enshi Hubei 445000,China)
出处
《局解手术学杂志》
2021年第10期846-852,共7页
Journal of Regional Anatomy and Operative Surgery
基金
武汉市卫计委2019年科研项目(S201912040082)。
