摘要
目的探讨尼达尼布联合参附注射液对百草枯(PQ)中毒所致肺损伤的保护作用。方法于2021年9月,将90只SD大鼠按随机数字表法分为对照组、PQ染毒组、参附注射液治疗组、尼达尼布治疗组和联合治疗组,每组各18只。对照组给予生理盐水灌胃,其余四组以20%PQ 80 mg/kg灌胃,参附注射液治疗组(12 ml/kg参附注射液)、尼达尼布治疗组(60 mg/kg尼达尼布)和联合治疗组(12 ml/kg参附注射液+60 mg/kg尼达尼布)于染毒6 h后开始每日一次药物干预。分别检测各组大鼠1、3、7 d时血清中转化生长因子β1(TGF-β1)、白介素-1β(IL-1β)水平,观察各组大鼠7 d时的肺组织病理学改变、肺组织湿重/干重比(W/D),观察超氧化物歧化酶(SOD)、丙二醛(MDA)在肺组织中的含量变化,Western印迹法检测肺组织中成纤维细胞生长因子受体1(FGFR1)、血小板衍化生长因子受体α(PDGFRα)以及血管内皮生长因子受体2(VEGFR2)的表达水平。结果各染毒组大鼠染毒后血清TGF-β1、IL-1β含量先上升后下降,联合治疗组1、3、7 d大鼠血清TGF-β1、IL-1β含量均明显低于同时间点PQ染毒组、参附注射液治疗组和尼达尼布治疗组(P<0.05);经药物治疗后第7天,肺组织病理切片显示参附注射液治疗组、尼达尼布治疗组和联合治疗组大鼠肺泡腔内出血、渗出、炎性细胞浸润程度均较PQ染毒组减轻,以联合治疗组大鼠肺损伤病变最轻;与对照组比较,PQ染毒组大鼠肺组织W/D升高,MDA含量升高,SOD含量降低,FGFR1、PDGFRα、VEGFR2蛋白表达水平升高(P<0.05);与PQ染毒组、参附注射液治疗组和尼达尼布治疗组比较,联合治疗组大鼠肺组织W/D明显降低,肺组织中MDA含量降低、SOD含量升高,FGFR1、PDGFRα、VEGFR2蛋白表达水平降低(P<0.05)。结论尼达尼布联合参附注射液可减轻PQ中毒大鼠急性肺损伤,可能与二者联合应用可以更好地抑制TGF-β1的激活及抑制FGFR1、PDGFRα、VEGFR2在大鼠肺组织的表达相关。
Objective To study the effects of Nintedanib associated with Shenfu Injection on lung injury induced by paraquat(PQ)intoxication.Methods In September 2021,a total of 90 SD rats were divided into 5 groups in random,namely control group,PQ poisoning group,Shenfu Injection group,Nintedanib group and associated group,18 rats in each group.Normal saline was given by gavage route to rats of control group,20%PQ(80 mg/kg)was administered by gavage route to rats of other four groups.6 hours after PQ gavage,Shenfu Injection group(12 ml/kg Shenfu Injection),Nintedanib group(60 mg/kg Nintedanib)and associated group(12 ml/kg Shenfu Injection and 60 mg/kg Nintedanib)were administered with medicine once a day.The levels of serum transforming growth factor beta1(TGF-β1),interleukin-1 beta(IL-1β)were determined at 1,3 and 7 d,respectively.The pathological changes of lung tissue,the ratio of wet weight and dry weight(W/D)of lung tissue,the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in lung tissue were observed and determined after 7 d.Western blot was used to analyse the expression levels of fibroblast growth factor receptor 1(FGFR1),platelet derivation growth factor receptor alpha(PDGFRα),vascular endothelial growth factor receptor 2(VEGFR2)in lung tissue after 7 d.Results The levels of TGF-β1,IL-1βin all poisoning groups went up first and then went down.The levels of TGF-β1,IL-1βin associated group at 1,3,7 d were lower than that of PQ poisoning group,Shenfu Injection group and Nintedanib group at the same point(P<0.05).Pathological changes of lung tissue under the light microscopes showed that the degrees of hemorrhage,effusion and infiltration of inflammatory cells inside the alveolar space of Shenfu Injection group,Nintedanib group and associated group were milder than that of PQ poisoning group,and the midest in associated group.Compared with control group,the W/D of lung tissue was higher,the level of MDA in lung tissue was higher,while the level of SOD was lower,the expressions of FGFR1,PDGFRαand VEGFR2 in lung tissue were higher in PQ poisoning group(P<0.05).Compared with PQ poisoning group,Shenfu Injection group and Nintedanib group,the W/D of lung tissue was lower,the level of MDA in lung tissue was lower,while the level of SOD was higher,the expressions of FGFR1,PDGFRαand VEGFR2 in lung tissue were lower in associated group(P<0.05).Conclusion Nintedanib associated with Shenfu Injection can relieve lung injury of rats induced by PQ,which may be related to Nintedanib associated with Shenfu Injection can inhibit the activation of TGF-β1 and the expressions of FGFR1,PDGFRα,VEGFR2 in lung tissue of rats.
作者
李海娜
刘畅
王金柱
孙家安
兰超
刘明科
Li Haina;Liu Chang;Wang Jinzhu;Sun Jiaan;Lan Chao;Liu Mingke(Department of Emergency Medicine,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450007,China)
出处
《中华劳动卫生职业病杂志》
CAS
CSCD
北大核心
2023年第2期81-86,共6页
Chinese Journal of Industrial Hygiene and Occupational Diseases
基金
2022年度河南省医学科技攻关计划联合共建项目(LHGJ20220860)
河南省高等学校重点科研项目计划(19A320093)
睿E(睿意)急诊医学研究专项基金(R2019027)。
关键词
百草枯
中毒
肺损伤
尼达尼布
抗炎
抗纤维化
Paraquat
Intoxication
Lung injury
Nintedanib
Anti-inflammatory
Anti-fibrosis
