AIM：To investigate the effect of anti-vascular epithelial growth factor（VEGF）agents on the expression of fibrosisrelated inflammatory mediators under normoxic and hypoxic conditions,and to further clarify the mecha...AIM：To investigate the effect of anti-vascular epithelial growth factor（VEGF）agents on the expression of fibrosisrelated inflammatory mediators under normoxic and hypoxic conditions,and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS：Human retinal pigment epithelial（RPE）cells were incubated under normoxic and hypoxic conditions.For hypoxia treatment,CoCl_2 at 200μmol/L was added to the media. ARPE-19 cells were treated as following：1）control group：no treatment; 2）bevacizumab group：bevacizumab at 0.25 mg/mL was added to the media; 3）hypoxia group：CoCl_2 at 200 μmol/L was added to the media; 4）hypoxia＋bevacizumab group：CoCl_2 at 200 μmol/L and bevacizumab at 0.25 mg/mL were added to the media.The expression of interleukin（IL）-1β,IL-6,IL-8 and tumor necrosis factor（TNF）-α were evaluated using real-time polymerase chain reaction（RT-PCR）and enzyme-linked immunosorbent assay（ELISA）at 6,12,24 and 48 h. RESULTS：Both m RNA and protein levels of IL-1β,IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point,and TNF-α gene and protein expression was only significantly higher only at 24 and 48h（P〈0.05）. Under hypoxic conditions,bevacizumab significantly increased the expression of IL-1β,IL-6,IL-8 and TNF-α at 6,12,24 and 48h（P〈0.05）. IL-1β,IL-8 and TNF-α peaked at 24 h and IL-6 peaked at 12 h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION：Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under bothnormoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after antiVEGF therapy,and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.展开更多
Objective:To investigate the therapeutic effect of Shihu(Dendrobium huoshanense,DH)on doxorubicin(DOX)-induced heart failure in mice and the involved mechanisms.Methods:Male C57BL/6 mice were randomly divided into 3 g...Objective:To investigate the therapeutic effect of Shihu(Dendrobium huoshanense,DH)on doxorubicin(DOX)-induced heart failure in mice and the involved mechanisms.Methods:Male C57BL/6 mice were randomly divided into 3 groups:Control(Ctrl)group,DOX group and DH group.Chronic heart failure was induced by intraperitoneal injection of doxorubicin solution.Mice in DH group were fed normal chow containing DH powder for 4 weeks.After 4-week treatment,electrocardiograms were measured.At the end of experiment,serum and heart sample were collected for determination of indicators for heart failure indicators.The heart tissues were conducted HE,Masson,Sirius red staining and TUNEL staining to determine cardiac tissue morphology,fibrosis,collagen content and apoptosis,respectively.mRNA and protein expression were determined by qRT-PCR and Western blot,respectively.Results:DH reduced the DOX-induced serum biomarkers(creatine kinase,aspartate aminotransferase and lactate dehydrogenase)of heart damage and reduced heart fibrosis.Mechanically,DH inhibited myocardial apoptosis,decreased interleukin 6 and tumor necrosis factoralevels,but increased superoxide dismutase 2 expression.Conclusion:DH alleviates DOX-induced chronic heart failure by inhibiting inflammatory pathway and enhancing anti-oxidative enzymes.Our study provides the potential of DH for heart failure treatment.展开更多
基金Supported by Shandong Provincial Natural Science Foundation,China(No.ZR2014HM029)
文摘AIM：To investigate the effect of anti-vascular epithelial growth factor（VEGF）agents on the expression of fibrosisrelated inflammatory mediators under normoxic and hypoxic conditions,and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS：Human retinal pigment epithelial（RPE）cells were incubated under normoxic and hypoxic conditions.For hypoxia treatment,CoCl_2 at 200μmol/L was added to the media. ARPE-19 cells were treated as following：1）control group：no treatment; 2）bevacizumab group：bevacizumab at 0.25 mg/mL was added to the media; 3）hypoxia group：CoCl_2 at 200 μmol/L was added to the media; 4）hypoxia＋bevacizumab group：CoCl_2 at 200 μmol/L and bevacizumab at 0.25 mg/mL were added to the media.The expression of interleukin（IL）-1β,IL-6,IL-8 and tumor necrosis factor（TNF）-α were evaluated using real-time polymerase chain reaction（RT-PCR）and enzyme-linked immunosorbent assay（ELISA）at 6,12,24 and 48 h. RESULTS：Both m RNA and protein levels of IL-1β,IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point,and TNF-α gene and protein expression was only significantly higher only at 24 and 48h（P〈0.05）. Under hypoxic conditions,bevacizumab significantly increased the expression of IL-1β,IL-6,IL-8 and TNF-α at 6,12,24 and 48h（P〈0.05）. IL-1β,IL-8 and TNF-α peaked at 24 h and IL-6 peaked at 12 h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION：Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under bothnormoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after antiVEGF therapy,and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.
基金the International Science&Technology Cooperation Programs of China(No.2017YFE0110100)the National Natural Science Foundation of China(No.81773727,81973316,81722046,and 31770863)+1 种基金Key Research and Development Program of Anhui Province(No.201904a07020007)the Fundamental Research Funds for the Central Universities to X Yang,Y Duan,and Y Chen.
文摘Objective:To investigate the therapeutic effect of Shihu(Dendrobium huoshanense,DH)on doxorubicin(DOX)-induced heart failure in mice and the involved mechanisms.Methods:Male C57BL/6 mice were randomly divided into 3 groups:Control(Ctrl)group,DOX group and DH group.Chronic heart failure was induced by intraperitoneal injection of doxorubicin solution.Mice in DH group were fed normal chow containing DH powder for 4 weeks.After 4-week treatment,electrocardiograms were measured.At the end of experiment,serum and heart sample were collected for determination of indicators for heart failure indicators.The heart tissues were conducted HE,Masson,Sirius red staining and TUNEL staining to determine cardiac tissue morphology,fibrosis,collagen content and apoptosis,respectively.mRNA and protein expression were determined by qRT-PCR and Western blot,respectively.Results:DH reduced the DOX-induced serum biomarkers(creatine kinase,aspartate aminotransferase and lactate dehydrogenase)of heart damage and reduced heart fibrosis.Mechanically,DH inhibited myocardial apoptosis,decreased interleukin 6 and tumor necrosis factoralevels,but increased superoxide dismutase 2 expression.Conclusion:DH alleviates DOX-induced chronic heart failure by inhibiting inflammatory pathway and enhancing anti-oxidative enzymes.Our study provides the potential of DH for heart failure treatment.
