玉郎伞多糖对大鼠放射性肺损伤的作用及机制研究
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摘要
目的:探讨玉郎伞多糖(YLSP)对大鼠放射性肺损伤的作用及机制。方法:将120只SD大鼠随机分为5组:正常对照组、单纯照射组及玉郎伞多糖低剂量(YLSPL)组、中剂量(YLSPM)组和高剂量(YLSPH)组,每组24只。YLSPL组、YLSPM组、YLSPH组分别按150mg/kg、300mg/kg、600mg/kg于照射前1周开始灌胃给予YLSP,正常对照组和单纯照射组给予等量生理盐水。单纯照射组和YLSP各给药组大鼠麻醉后用DTγ射线单次20Gy照射大鼠右肺,正常对照组仅麻醉不予照射。分别于照射后第10、第40、第70天,每组取8只大鼠行腹主动脉取血并处死,采用酶联免疫吸附试验(ELISA)法检测血清转化生长因子β1(TGF-β1)和白细胞介素-6(IL-6)含量;取出双肺,计算湿肺系数;采用苏木精—伊红(HE)染色法观察肺组织病理学改变;检测肺组织超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量;荧光定量PCR(qPCR)法检测Smad2mRNA相对表达量。结果:正常对照组肺组织及肺泡结构完好,无充血、渗出、水肿等;单纯照射组照射后早期出现充血、水肿、炎症细胞浸润、肺泡间隔增宽,之后肺组织纤维化加重、肺泡腔变小、消失;YLSP各给药组肺组织病理明显改善。照射后,YLSP各给药组大鼠血清TGF-β1和IL-6含量、Smad2mRNA相对表达量及肺组织MDA含量均下降,肺组织SOD活性升高,以YLSPH组最为显著(P<0.05)。YLSP各给药组湿肺系数照射后第10、第40、第70天均显著下降(均P<0.05)。结论:YLSP对放射性肺损伤大鼠有保护作用,其机制可能与降低血清TGF-β1及IL-6含量、下调Smad2mRNA表达、抗自由基和抑制脂质过氧化损伤作用有关。
Objective:To explore the effect and mechanisms of Yulangsan polysaccharides(YLSP)on radiation-induced lung injury in rats.Methods:120 SD rats were randomly divided into 5 groups(n=24 each)and oral gavaged:a normal control group(normal saline),a model group(normal saline),and three different doses of YLSP groups(150 mg/kg,300 mg/kg,600 mg/kg).The rats in the model group and YLSP groups received 20 Gy gamma-radiation to induce acute lung injury.After 10,40 and 70 days of radiation,the levels of transforming growth factorβ1(TGF-β1)and interleukin-6(IL-6)in serum,the superoxide dismutase(SOD)activity and malondialdehyde(MDA)content in lung tissues were detected.The wet lung coefficient was calculated.HE staining was performed to observe the pathological changes.Fluorescent quantitative PCR(qPCR)was used to determine the mRNA expression of Smad2.Results:Alveolar structure of lung tissues in the control group was intact without edema and exudation.Pathological changes in the lung tissue of model group rats exhibited early hyperemia,edema,collagen deposition,inflammatory cell infiltration,thickened alveolar septum, then aggravated pulmonary fibrosis and smaller alveolar space.The lung histopathology of YLSP groups was obviously improved.Compared with the model group,the serum TGF-β1 and IL-6 levels,lung tissue MDA content,and Smad2 mRNA expression were decreased,while the SOD activity was increased in different doses of YLSP groups,and these improvement of high dose group were the most significant.The wet lung coefficient of YLSP groups was decreased significantly at three time points after irradiation.Conclusion:YLSP could protect the rats against radiation-induced lung injury.The mechanism might be related to the reduction of TGF-β1 and IL-6 levels,antagonism of free-radical,and the inhibition of lipid peroxidation.
Objective:To explore the effect and mechanisms of Yulangsan polysaccharides(YLSP)on radiation-induced lung injury in rats.Methods:120 SD rats were randomly divided into 5 groups(n=24 each)and oral gavaged:a normal control group(normal saline),a model group(normal saline),and three different doses of YLSP groups(150 mg/kg,300 mg/kg,600 mg/kg).The rats in the model group and YLSP groups received 20 Gy gamma-radiation to induce acute lung injury.After 10,40 and 70 days of radiation,the levels of transforming growth factorβ1(TGF-β1)and interleukin-6(IL-6)in serum,the superoxide dismutase(SOD)activity and malondialdehyde(MDA)content in lung tissues were detected.The wet lung coefficient was calculated.HE staining was performed to observe the pathological changes.Fluorescent quantitative PCR(qPCR)was used to determine the mRNA expression of Smad2.Results:Alveolar structure of lung tissues in the control group was intact without edema and exudation.Pathological changes in the lung tissue of model group rats exhibited early hyperemia,edema,collagen deposition,inflammatory cell infiltration,thickened alveolar septum, then aggravated pulmonary fibrosis and smaller alveolar space.The lung histopathology of YLSP groups was obviously improved.Compared with the model group,the serum TGF-β1 and IL-6 levels,lung tissue MDA content,and Smad2 mRNA expression were decreased,while the SOD activity was increased in different doses of YLSP groups,and these improvement of high dose group were the most significant.The wet lung coefficient of YLSP groups was decreased significantly at three time points after irradiation.Conclusion:YLSP could protect the rats against radiation-induced lung injury.The mechanism might be related to the reduction of TGF-β1 and IL-6 levels,antagonism of free-radical,and the inhibition of lipid peroxidation.
引文
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[13]李轩.CpG ODN1826对小鼠放射性肺损伤作用研究[D].上海:复旦大学,2014.
[2]吕鹏,陈兆霓,陈春霞,等.3种天然化合物联合对四氯化碳诱导的大鼠肝纤维化的影响[J].中国实验方剂学杂志,2011,17(13):149-152.
[3]陶丽群,左巧云,李秀菊,等.复方玉郎伞多糖对鸭乙型肝炎病毒诱导的肝损伤的影响[J].中国实验方剂学杂志,2014,20(5):172-176.
[4]段小群.玉郎伞多糖抗肝纤维化作用及机制的研究[D].南宁:广西医科大学,2006.
[5]GIRIDHAR P,MALLICK S,RATH G K,et al.Radiation induced lung injury:prediction,assessment and management[J].Asian Pac J Cancer Prev,2015,16(7):2613-2617.
[6]SIMONE C B.Thoracic radiation normal tissue injury[J].Semin Radiat Oncol,2017,27(4):370-377.
[7]FINKELSTEIN J N,JOHNSTON C J,WILLIAMS J P.Treatment for radiation-induced pulmonary late effects:spoiled for choice or looking in the wrong direction[J].Curr Drug Targets,2010(11):1386-1394.
[8]ROSENZWEIG K E,ZAUDERER MCP LASER B,KRUG L M,et al.Pleural intensity-modulated radiotherapy for malignant pleural mesothelioma[J].Int JRadiat Oncol Biol Ps,2012,83(4):1278-1283.
[9]阮文富,梁杏梅,段文明,等.玉郎伞多糖对双氯芬酸钠致小鼠肝损伤的保护作用及相关机制研究[J].重庆医科大学学报,2015,40(10):1352-1356.
[10]KIAZIMOV K I.Pathogenesis,diagnostics and treatment of radiation pneumonitis induced by radiotherapy of lung cancer[J].Georgian Med News,2009(174):115-118.
[11]衷敬华.百令胶囊对放射性肺损伤保护作用的基础与临床研究[D].广州:南方医科大学,2013.
[12]郑爱青,韩晨光,朱新英,等.IL-1和IL-6在放射性肺损伤发病中的作用[J].武警医学院学报,2009,118(3):194-196.
[13]李轩.CpG ODN1826对小鼠放射性肺损伤作用研究[D].上海:复旦大学,2014.