氟比洛芬酯对放射性心脏损伤模型大鼠NF-κB/TGF-β1信号通路的影响  

Effects of flurbiprofen axetil on NF-κB/TGF-β1 signaling pathway in rats with radiation-induced heart disease

作　　者：何平[1] 赵燕 王海东[1] 赵栋[1] 王云 HE Ping;ZHAO Yan;WANG Haidong;ZHAO Dong;WANG Yun(Department of Anesthesiology,Gansu Cancer Hospital,Lanzhou 730050,China)

机构地区：[1]甘肃省肿瘤医院麻醉科,兰州730050

出　　处：《中国免疫学杂志》2023年第5期945-950,共6页Chinese Journal of Immunology

摘　　要：目的:探究氟比洛芬酯(FA)对放射性心脏损伤(RIHD)模型大鼠NF-κB/TGF-β1信号通路的影响。方法:50只大鼠按随机数字法分为对照组、照射组、FA低剂量组、FA中剂量组、FA高剂量组,每组10只。除对照组不照射外,其余各组心脏照射20 Gy,放疗结束当天给药,FA低、中、高剂量组尾静脉分别注射5、10、20 mg/kg FA,直至放疗后4周结束。试剂盒检测大鼠血清中肌钙蛋白T(cTnT)、肌酸激酶同工酶(CK-MB)水平、心肌组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、髓过氧化物酶(MPO)活性;HE染色观察大鼠心肌组织形态;ELISA检测血清中TNF-α、IL-6、IL-10水平;RT-qPCR和免疫组化检测心肌组织中NF-κB、TGF-β1 mRNA和蛋白水平。结果:照射组大鼠心肌细胞出现明显水肿现象、心肌缺血、坏死严重,并伴有大量炎症浸润,横肌消失,核固缩或溶解;随着FA剂量升高,细胞逐渐恢复正常,排列规律,仅出现少量炎症浸润现象。与对照组相比,照射组血清中cTnT、CK-MB、TNF-α、IL-6水平、心肌组织病理评分、心肌组织中MDA含量、MPO活性,NF-κB、TGF-β1 mRNA水平和蛋白平均积分吸光度升高(P<0.05),血清中IL-10水平,心肌组织中SOD活性降低(P<0.05);FA能降低血清中cTnT、CK-MB、TNF-α、IL-6水平、心肌组织病理评分、心肌组织中MDA含量、MPO活性,NF-κB、TGF-β1 mRNA水平和蛋白平均积分吸光度,提高血清中IL-10水平及心肌组织中SOD活性。结论:FA可缓解RIHD心肌组织炎症损伤,可能与抑制NF-κB/TGF-β1信号通路有关。Objective:To explore the effect of flurbiprofen axetil(FA)on NF-κB/TGF-β1 signaling pathway in rats with radiation-induced heart disease(RIHD).Methods:Fifty rats were randomly divided into control group,irradiation group,FA low-dose group,FA medium-dose group,FA high-dose group based on random number table method,with 10 rats in each group.Except for control group,which was not irradiated,other groups were irradiated with 20 Gy to heart and administered on the day of the end of radiotherapy.FA low,medium and high dose groups were injected with 5,10,20 mg/kg FA into the tail vein respectively until 4 weeks after radiotherapy the end.Kits were used to detect serum levels of troponin T(cTnT),creatine kinase isoenzyme(CK-MB),superoxide dismutase(SOD)activity,malondialdehyde(MDA)content and myelopathy in myocardial tissue oxidase(MPO)activity of rats;HE staining was used to observe myocardial tissue morphology of rats;ELISA was used to detect levels of serum TNF-α,IL-6 and IL-10;RT-qPCR and immunohistochemistry were used to detect levels of NF-κB and TGF-β1 mRNA and protein in myocardial tissue.Results:In irradiation group,myocardial cells showed obvious edema,myocardial ischemia,and severe necrosis,accompanied by a large number of inflammatory infiltrations,disappearance of transverse muscles,and nuclear pyknosis or dissolution;as the dose of FA increased,cells were gradually returned to normal,arranged regularly,and only a small amount of inflammatory infiltration appeared.Compared with control group,serum cTnT,CK-MB,TNF-α,IL-6 levels,myocardial tissue pathology score,myocardial tissue MDA content,MPO activity,NF-κB,TGF-β1 mRNA levels and protein average integrated absorbance in irradiation group were increased(P<0.05),while serum IL-10 level and SOD activity in myocardial tissue were decreased(P<0.05);FA could reduce serum cTnT,CK-MB,TNF-α,IL-6 levels,myocardial tissue pathology score,myocardial tissue MDA content,MPO activity,NF-κB,TGF-β1 mRNA levels and protein average integrated absorbance,and increas

关 键 词：氟比洛芬酯 放射性心脏损伤 NF-κB/TGF-β1信号通路 

分 类 号：R614[医药卫生—麻醉学]