Objective:Radiotherapy is used to treat patients with tumors;however,radiation(IR)-induced testicular injury,which has no effective treatment approved in clinical practice,significantly influences their prognosis and ...Objective:Radiotherapy is used to treat patients with tumors;however,radiation(IR)-induced testicular injury,which has no effective treatment approved in clinical practice,significantly influences their prognosis and quality of life.The protective effects and underlying mechanisms of action of isofraxidin(IF)against IR-induced testicular injury were investigated.Methods:A mouse testis injury model was established using 5 Gy irradiation.Hematoxylin and eosin(H&E)staining,immunofluorescence staining,and enzyme-linked immunosorbent assay were used to measure DNA damage,apoptosis,inflammatory reactions,and oxidative stress in the testes of mice after irradiation.The effectiveness of IF irradiation on testicular injury was evaluated,and the mechanisms of the related oxidative stress and inflammatory response pathways were discussed.Results:IF can improve IR-induced testicular injury by inhibiting the increased levels of DNA damage,apoptosis rate,oxidative stress,and inflammatory factors.The radioprotective effects of IF on testicular injury are mediated by the stimulation of nuclear factor E2-related factor 2(Nrf2)/heme oxidase-1(HO-1)or suppression of NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome signaling pathways.In addition,crosstalk between the Nrf2/HO-1 and NLRP3 inflammasome signaling pathways was elucidated,in which the inhibition of the NLRP3 inflammasome was mediated by the activation of Nrf2 signaling with IF upon IR exposure.Conclusion:IF can be a potent radioprotective agent to mitigate testicular damage,and may provide a new therapeutic option to alleviate the side effects of radiotherapy in male patients with tumors.展开更多
研究刺五加注射液中3个活性成分,紫丁香苷、刺五加苷E及异嗪皮啶在大鼠体内的药动学行为,并与相应单体分别经静脉注射给药后大鼠体内药动学行为比较。将24只雄性大鼠随机分为4组,分别经静脉注射给予紫丁香苷、刺五加苷E、异嗪皮啶及相...研究刺五加注射液中3个活性成分,紫丁香苷、刺五加苷E及异嗪皮啶在大鼠体内的药动学行为,并与相应单体分别经静脉注射给药后大鼠体内药动学行为比较。将24只雄性大鼠随机分为4组,分别经静脉注射给予紫丁香苷、刺五加苷E、异嗪皮啶及相当剂量的刺五加注射液。采用液相色谱-串联四级杆质谱(liquid chromatography tandem mass spectrometry,LC-MS/MS)法测定不同时间点血浆中紫丁香苷、刺五加苷E及异嗪皮啶的浓度并采用DAS 2.0数据处理软件及SPSS 17.0统计软件分别进行药动学参数计算及比较。静脉给药后,3种单体成分与刺五加注射液主要药动学参数如血药浓度-时间曲线下面积(AUC)、血浆清除率(CL)、消除半衰期(t1/2)等存在显著性差异(P<0.05)。刺五加注射液中紫丁香苷AUC较单体给药组明显增大,CL较单体给药组明显减小;刺五加苷E的AUC较单体给药组明显减小,CL较单体给药组明显增大;注射液中异嗪皮啶较单体给药组t1/2延长。可见与单体给药相比,刺五加注射液中紫丁香苷、刺五加苷E及异嗪皮啶大鼠体内的代谢动力学过程存在差异。刺五加注射液中的其他共存成分可能对单个有效成分的主要药动学参数产生影响。展开更多
基金National Natural Science Foundation of China(82192911,82103776)Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202207).
文摘Objective:Radiotherapy is used to treat patients with tumors;however,radiation(IR)-induced testicular injury,which has no effective treatment approved in clinical practice,significantly influences their prognosis and quality of life.The protective effects and underlying mechanisms of action of isofraxidin(IF)against IR-induced testicular injury were investigated.Methods:A mouse testis injury model was established using 5 Gy irradiation.Hematoxylin and eosin(H&E)staining,immunofluorescence staining,and enzyme-linked immunosorbent assay were used to measure DNA damage,apoptosis,inflammatory reactions,and oxidative stress in the testes of mice after irradiation.The effectiveness of IF irradiation on testicular injury was evaluated,and the mechanisms of the related oxidative stress and inflammatory response pathways were discussed.Results:IF can improve IR-induced testicular injury by inhibiting the increased levels of DNA damage,apoptosis rate,oxidative stress,and inflammatory factors.The radioprotective effects of IF on testicular injury are mediated by the stimulation of nuclear factor E2-related factor 2(Nrf2)/heme oxidase-1(HO-1)or suppression of NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome signaling pathways.In addition,crosstalk between the Nrf2/HO-1 and NLRP3 inflammasome signaling pathways was elucidated,in which the inhibition of the NLRP3 inflammasome was mediated by the activation of Nrf2 signaling with IF upon IR exposure.Conclusion:IF can be a potent radioprotective agent to mitigate testicular damage,and may provide a new therapeutic option to alleviate the side effects of radiotherapy in male patients with tumors.
文摘研究刺五加注射液中3个活性成分,紫丁香苷、刺五加苷E及异嗪皮啶在大鼠体内的药动学行为,并与相应单体分别经静脉注射给药后大鼠体内药动学行为比较。将24只雄性大鼠随机分为4组,分别经静脉注射给予紫丁香苷、刺五加苷E、异嗪皮啶及相当剂量的刺五加注射液。采用液相色谱-串联四级杆质谱(liquid chromatography tandem mass spectrometry,LC-MS/MS)法测定不同时间点血浆中紫丁香苷、刺五加苷E及异嗪皮啶的浓度并采用DAS 2.0数据处理软件及SPSS 17.0统计软件分别进行药动学参数计算及比较。静脉给药后,3种单体成分与刺五加注射液主要药动学参数如血药浓度-时间曲线下面积(AUC)、血浆清除率(CL)、消除半衰期(t1/2)等存在显著性差异(P<0.05)。刺五加注射液中紫丁香苷AUC较单体给药组明显增大,CL较单体给药组明显减小;刺五加苷E的AUC较单体给药组明显减小,CL较单体给药组明显增大;注射液中异嗪皮啶较单体给药组t1/2延长。可见与单体给药相比,刺五加注射液中紫丁香苷、刺五加苷E及异嗪皮啶大鼠体内的代谢动力学过程存在差异。刺五加注射液中的其他共存成分可能对单个有效成分的主要药动学参数产生影响。
