肺宁颗粒对放射性肺损伤大鼠细胞因子的影响
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摘要
目的利用大鼠急性放射性肺损伤(RILI)模型,研究肺宁颗粒对肺损伤及炎症因子的影响。方法采用大鼠胸部接受6 MV X线单次照射15 Gy,1周2次,共30 Gy,构建放射引起的肺损伤模型,不同时间段灌注不同剂量的肺宁颗粒。采用CT法检测肺损伤程度,HE染色法检测放疗后各时间段每组大鼠的肺组织的病理变化,ELISA法检测照射后的大鼠血浆中炎症因子的含量变化。结果成功构建放射性肺损伤模型,放疗时间越长肺部损伤程度及炎症因子释放含量越多。放疗后第2、4、6周放射性肺损伤组大鼠肺组织转化生长因子-β1(TGF-β1)、白介素-1(IL-1)、白介素-6(IL-6)强表达,显著高于Con组(正常组)(P<0.05)。不同放疗时间的大鼠肺组织经肺宁颗粒处理后TGF-β1、IL-1、IL-6含量明显低于各对照组(P<0.05),且呈一定浓度依赖性。肺宁颗粒高剂量组、肺宁颗粒中剂量组、肺宁颗粒低剂量组TGF-β1、IL-1、IL-6表达均不同程度高于地塞米松组(P<0.05),肺宁颗粒预防组上述指标表达低于地塞米松组(P<0.05)。结论肺宁颗粒主要通过降低炎症因子TGF-β1、IL-1、IL-6的产生从而防治放射性肺损伤。肺宁颗粒治疗作用低于地塞米松,但肺宁颗粒的预防作用优于地塞米松。
Objective To investigate the effect of Feining granule on lung injury and inflammatory factors in rats in a ratmodel of acute radiation-induced lung injury(RILI). Methods In this experiment,a full-thoracic 6 MV X-ray singleirradiation 15 Gy,twice a week,and the dose is 30 Gy,used to construct a rat model of radiation-induced lung injury,andthe dose of Feining granules was infused at different time points. The degree of lung injury was detected by CT method. Thepathological changes of lung tissue in rats of different groups after radiotherapy were detected by HE staining.The changes ofplasma inflammatory factors were detected by ELISA. Results(1)A model of radiation-induced lung injury was successfullyconstructed. The longer the radiotherapy time,the more the degree of lung injury and the release of inflammatory factors.(2)The expression levels of TGF-β1,IL-1 and IL-6 in lung tissue of rats in RILI group was significantly higher than those inthe control group at the 2 nd,4 th and 6 th week after radiotherapy(P<0.05). The expression levels of TGF-β1,IL-1 and IL-6 in lung tissue of rats at different time points after treated with Feining granule were significantly lower than those in thesimultaneous model group(P<0.05),and it was concentration-dependent. However,the expressions levels of TGF-β1,IL-1 and IL-6 in high group,medium group and low group were higher than those in dexamethasone group(P<0.05),while thosein prevention group were lower than those in dexamethasone group(P<0.05). Conclusion Feining granule could preventand treat radiation-induced lung injury by reducing the expression levels of TGF-β1,IL-1 and IL-6. The treatment ofFeining granules was not as effective as dexamethasone,but the efficacy of Feining granules was better than that ofdexamethasone.
Objective To investigate the effect of Feining granule on lung injury and inflammatory factors in rats in a ratmodel of acute radiation-induced lung injury(RILI). Methods In this experiment,a full-thoracic 6 MV X-ray singleirradiation 15 Gy,twice a week,and the dose is 30 Gy,used to construct a rat model of radiation-induced lung injury,andthe dose of Feining granules was infused at different time points. The degree of lung injury was detected by CT method. Thepathological changes of lung tissue in rats of different groups after radiotherapy were detected by HE staining.The changes ofplasma inflammatory factors were detected by ELISA. Results(1)A model of radiation-induced lung injury was successfullyconstructed. The longer the radiotherapy time,the more the degree of lung injury and the release of inflammatory factors.(2)The expression levels of TGF-β1,IL-1 and IL-6 in lung tissue of rats in RILI group was significantly higher than those inthe control group at the 2 nd,4 th and 6 th week after radiotherapy(P<0.05). The expression levels of TGF-β1,IL-1 and IL-6 in lung tissue of rats at different time points after treated with Feining granule were significantly lower than those in thesimultaneous model group(P<0.05),and it was concentration-dependent. However,the expressions levels of TGF-β1,IL-1 and IL-6 in high group,medium group and low group were higher than those in dexamethasone group(P<0.05),while thosein prevention group were lower than those in dexamethasone group(P<0.05). Conclusion Feining granule could preventand treat radiation-induced lung injury by reducing the expression levels of TGF-β1,IL-1 and IL-6. The treatment ofFeining granules was not as effective as dexamethasone,but the efficacy of Feining granules was better than that ofdexamethasone.
引文
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[17]Cameron BD,Sekhar KR,Ofori M,et al.The role of Nrf2 in the response to normal tissue radiation injury[J].Radiat Res,2018,190(2):99-106.273
[18]Forel JM,Guervilly C,Farnarier C,et al.Transforming growth factor-β1 in predicting early lung fibroproliferation in patients with acute respiratory distress syndrome[J].PLoS One,2018,13(11):e0206105.
[19]金崇强,全莹,刘海丽,等.中医防治放疗辐射所致骨髓抑制的研究进展[J].台州学院学报,2017,39(6):18-21.
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[21]戴芳芳,崔勇,李冠龙,等.放射性肺炎的发病机制及中西医结合治疗进展[J].现代中西医结合杂志,2018,27(6):678-681.
[22]王策.肺宁颗粒对大鼠放射性肺炎及细胞因子表达的影响[J].中医临床研究,2017,9(22):21-24.
[2]贾全凡,袁龙,刘冬梅,等.BIRC5、NEIL2表达水平与鼻咽癌放疗敏感性的相关性[J].热带医学杂志,2018,18(10):1322-1325.
[3]Yamamoto T,Kadoya N,Morishita Y,et al.Assessment and agreement of the CT appearance pattern and its severity grading of radiation-induced lung injury after stereotactic body radiotherapy for lung cancer[J].PLoS One,2018,13(10):e0204734.
[4]Chen Z,Wu Z,Ning W,et al.Advances in molecular mechanisms and treatment of radiation-induced pulmonary fibrosis[J].Transl Oncol,2018,12(1):162-169.
[5]田金徽,施树珍,赵晔,等.中药干预放射性肺损伤规律的复杂网络分析[J].中国中药杂志,2018,43(14):3018-3025.
[6]Beach TA,Groves AM,Williams JP,et al.Modeling radiationinduced lung injury:lessons learned from whole thorax irradiation[J].Int J Radiat Biol,2018:1-16.
[7]Lu C,Lei Z,Wu H,et al.Evaluating risk factors of radiation pneumonitis after stereotactic body radiation therapy in lung tumor:Meta-analysis of 9 observational studies[J].PLoS One,2018,13(12):e0208637.
[8]胡彦辉,于卫江,耿良.痰热清注射液治疗放射性肺炎患者对体内细胞及肺纤维化的影响研究[J].中华中医药学刊,2018,36(1):61-63.
[9]Groves AM,Williams JP,Hernady E,et al.A potential biomarker for predicting the risk of radiation-induced fibrosis in the lung[J].Radiat Res,2018,190(5):513-525.
[10]Li L,Mok H,Jhaveri P,et al.Anticancer therapy and lung injury:molecular mechanisms[J].Expert Rev Anticancer Ther,2018,18(10):1041-1057.
[11]Jain V,Berman AT.Radiation pneumonitis:old problem,new tricks[J].Cancers(Basel),2018,10(7):e222.
[12]Bledsoe TJ,Nath SK,Decker RH.Radiation pneumonitis[J].Clin Chest Med,2017,38(2):201-208.
[13]Forel JM,Guervilly C,Farnarier C,et al.Transforming Growth Factor-β1 in predicting early lung fibroproliferation in patients with acute respiratory distress syndrome[J].PLoS One,2018,13308with acute respiratory dist(11):e0206105.
[14]Wang S,Campbell J,Stenmark MH,et al.Plasma levels of IL-8 and TGF-β1 predict radiation-induced lung toxicity in nonsmall cell lung cancer:a validation study[J].Int J Radiat Oncol Biol Phys,2017,98(3):615-621.
[15]Shen ZT,Shen JS,Ji XQ,et al.TGF-beta1 rs1982073polymorphism contributes to radiation pneumonitis in lung cancer patients:a meta-analysis[J].J Cell Mol Med,2016,20(12):2405-2409.
[16]Zhang C,Zeng W,Yao Y,et al.Naringenin ameliorates radiationinduced lung injury by lowering IL-1βlevel[J].J Pharmacol Exp Ther,2018,366(2):341-348.
[17]Cameron BD,Sekhar KR,Ofori M,et al.The role of Nrf2 in the response to normal tissue radiation injury[J].Radiat Res,2018,190(2):99-106.273
[18]Forel JM,Guervilly C,Farnarier C,et al.Transforming growth factor-β1 in predicting early lung fibroproliferation in patients with acute respiratory distress syndrome[J].PLoS One,2018,13(11):e0206105.
[19]金崇强,全莹,刘海丽,等.中医防治放疗辐射所致骨髓抑制的研究进展[J].台州学院学报,2017,39(6):18-21.
[20]练祖平,谢有科,白广德.中医药防治放射性肺损伤的研究进展[J].广西中医药,2018,41(4):68-70.
[21]戴芳芳,崔勇,李冠龙,等.放射性肺炎的发病机制及中西医结合治疗进展[J].现代中西医结合杂志,2018,27(6):678-681.
[22]王策.肺宁颗粒对大鼠放射性肺炎及细胞因子表达的影响[J].中医临床研究,2017,9(22):21-24.