尼达尼布联合参附注射液对大鼠百草枯中毒肾损伤的保护作用  

Effects of Nintedanib combined with Shenfu injection on kidney injury of the rats induced by paraquat intoxication

作　　者：李海娜 刘畅 齐晓艳 孙家安 兰超[2] Li Hai-na;Liu Chang;Qi Xiao-yan;Sun Jia-an;Lan Chao(Department of Emergency Medicine,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450007,China)

机构地区：[1]郑州大学附属郑州中心医院急诊科,河南郑州450007 [2]郑州大学第一附属医院急诊医学部,河南郑州450002

出　　处：《中国急救医学》2023年第3期225-229,共5页Chinese Journal of Critical Care Medicine

基　　金：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)。

摘　　要：目的 研究尼达尼布联合参附注射液对大鼠百草枯(PQ)中毒所致肾损伤的保护作用。方法 将90只SD大鼠按随机数字表法分为A、B、C、D、E组,其中A组为正常对照组,B组为PQ染毒对照组,C组为参附注射液治疗组,D组为尼达尼布治疗组,E组为参附注射液联合尼达尼布治疗组,每组18只。B、C、D、E组给予20%PQ 80 mg/kg灌胃制备大鼠急性PQ中毒模型,A组给予等量生理盐水灌胃。C、D、E组在PQ灌胃后6 h开始每日给予药物干预,A组和B组在相同时点给予等量生理盐水,分别在不同处理后第1、3、7天时处死大鼠。观察血清中转化生长因子-β1(TGF-β1)、白细胞介素-1β(IL-1β)水平,取肾组织,通过苏木精-伊红(HE)染色在光镜下观察肾组织病理变化。Western blot印迹方法检测肾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 (1)药物治疗后第1、3、7天,与A组比较,B、C、D、E组TGF-β1、IL-1β均升高(P<0.05)。与B组比较,C、D、E组TGF-β1、IL-1β均降低,其中以E组各指标降低最为明显(P<0.05)。(2)药物治疗后第7天,与B组比较,C、D、E组FGFR1、PDGFRα、VEGFR2表达水平均降低(P<0.05)。(3)药物治疗后第7天,光镜下观察肾组织病理切片显示C、D、E组大鼠肾小球及肾小管损伤程度均比B组减轻,E组大鼠肾损伤病变最轻。结论 与单用参附注射液或尼达尼布相比两者联合用药减轻大鼠PQ中毒急性肾损伤的效果更明显。Objective To study the effects of Nintedanib combined with Shenfu injection on kidney injury induced by paraquat(PQ) intoxication. Methods A total of 90 Wistar rats were divided into 5 groups at random, namely control group(A group, n=18), PQ poisoning group(B group, n=18), Shenfu injection group(C group, n=18), Nintedanib group(D group, n=18) and Nintedanib combined with Shenfu injection group(E group, n=18). PQ(80 mg/kg) was administered by gavage route to rats of group B, C, D and E for PQ poisoning models, equivalent normal saline was given in group A. At 6 hours after PQ gavage, group C, D and E were respectively administered with Shenfu injection, Nintedanib, Nintedanib and Shenfu injection once a day, while saline instead were administered to group A and B until they were sacrificed for experiment. 6 rats in each group were sacrificed at each time interval of 1, 3 and 7 days. The levels of transforming growth factor-β1(TGF-β1) and interleukin-1β(IL-1β) were determined. Then, the specimen of kidney tissue was prepared for microscopy observation. Western blot was used to analyse fibroblast growth factor receptor 1(FGFR1), platelet-derived growth factor receptor α(PDGFRα), vascular endothelial growth factor receptor 2(VEGFR2) expression levels in kidney tissue. Results(1)The levels of TGF-β1, IL-1β in group B, C, D and E were higher than those in group A on the 1st, 3rd, 7th day(P<0.05). Compared with group B, the levels of TGF-β1, IL-1 β in group C, D and E were lower, and the group E showed most evidently(P<0.05).(2)The expression of FGFR1, PDGFRα, VEGFR2 in kidney tissue of group C, D and E were lower than those in group B on the 7th day(P<0.05).(3)Pathological changes of renal tissue under the light microscopes showed that the damage degree of glomerulus and renal tubule in group C, D and E was milder than that in group B on the 7th day, and the injury in group E was the mildest. Conclusions Compared with Nintedanib or Shenfu injection, Nintedanib combined with Shenfu injection is better for re

关 键 词：百草枯(PQ) 中毒 肾损伤 尼达尼布 抗炎 抗纤维化 

分 类 号：R595.4[医药卫生—内科学]