OBJECTIVE The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo,as well as the potential mechanisms.METHODS First,the model of C6 glioma in Wistar rats w...OBJECTIVE The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo,as well as the potential mechanisms.METHODS First,the model of C6 glioma in Wistar rats was established and verified by hemotoxylin and eosin staining,immunohistochemical staining and magnetic resonance imaging(MRI).Then different doses of lapachol were gavaged and tumor volumes of the C6 glioma were detected by MRI.The effects of lapachol on C6 cell proliferation,apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)/phen-azinemethosulfate(PMS)assay,Hoechst33358 staining,AnnexinⅤ-FITC/PI staining,and comet assay.Effects of lapachol on topoisomeraseⅠ(TOPⅠ)and topoisomeraseⅡ(TOPⅡ)activities were detected by TOPⅠand TOPⅡmediated supercoiled p BR322 DNA relaxation assay.Molecular docking was used to predict the interaction of lapachol-TOPⅠand lapachol-TOPⅡ.TOP I and TOPⅡexpression levels in C6 cells were determined by Enzymelinked immunosorbent assay kits and real-time polymerase chain reaction(RT-PCR).RESULTS The rat C6 glioma model was successfully established.High dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats(P<0.05).MTS/PMS assay,Hoechst 33258 staining,AnnexinⅤ-FITC/PI staining,and comet assay showed that lapachol could inhibit proliferation,induce apoptosis and DNA damage of C6 cells in dose dependent manners.Lapachol could inhibit the activities of both TOPⅠandⅡ.Molecular docking showed that lapachol-TOPⅠshowed relatively stronger interaction than that of lapachol-TOPⅡ.Enzyme-linked immunosorbent assay and RT-PCR showed that lapachol could inhibit TOPⅡexpression levels,but not TOPⅠexpression levels.CONCLUSION These results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro,which might be related with inhibiting TOPⅠand TOPⅡactivities,as wel as TOPⅡexpression.展开更多
横波可控震源振动器平板作为页岩气勘探中的关键部件,其疲劳寿命直接影响可控震源的使用寿命和勘探精度。然而,传统的振动器平板疲劳寿命优化方法未考虑平板与平板齿间焊接残余应力的影响,导致平板结构在抗疲劳优化设计方面效果不佳。为...横波可控震源振动器平板作为页岩气勘探中的关键部件,其疲劳寿命直接影响可控震源的使用寿命和勘探精度。然而,传统的振动器平板疲劳寿命优化方法未考虑平板与平板齿间焊接残余应力的影响,导致平板结构在抗疲劳优化设计方面效果不佳。为此,使用局部灵敏度法对平板疲劳寿命进行敏感性分析,确定了焊接残余应力为影响疲劳寿命的关键因素。随后,建立了平板的各向最大焊接残余应力与焊接速度和焊接层间温度之间的数学模型,并以各向最大焊接残余应力为约束,以疲劳寿命为优化目标,建立相应的优化模型。最后,利用NSGA-Ⅱ(nondominated sorting genetic algorithm-Ⅱ,非支配排序遗传算法-Ⅱ)获取Pareto解集,并结合熵权法和TOPSIS(technique for order preference by similarity to ideal solution,逼近理想解排序)法确定最佳优化方案:焊接速度为10.23 mm/s,焊接层间温度为105℃。结果表明,优化后平板的疲劳寿命为10.23年,相比优化前提高了17.72%。研究结果可为横波可控震源振动器平板的疲劳寿命优化提供科学有效的理论方法和工程指导。展开更多
文摘OBJECTIVE The aim of this study is to investigate the inhibitory effects of lapachol on rat C6 glioma both in vitro and in vivo,as well as the potential mechanisms.METHODS First,the model of C6 glioma in Wistar rats was established and verified by hemotoxylin and eosin staining,immunohistochemical staining and magnetic resonance imaging(MRI).Then different doses of lapachol were gavaged and tumor volumes of the C6 glioma were detected by MRI.The effects of lapachol on C6 cell proliferation,apoptosis and DNA damage were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)/phen-azinemethosulfate(PMS)assay,Hoechst33358 staining,AnnexinⅤ-FITC/PI staining,and comet assay.Effects of lapachol on topoisomeraseⅠ(TOPⅠ)and topoisomeraseⅡ(TOPⅡ)activities were detected by TOPⅠand TOPⅡmediated supercoiled p BR322 DNA relaxation assay.Molecular docking was used to predict the interaction of lapachol-TOPⅠand lapachol-TOPⅡ.TOP I and TOPⅡexpression levels in C6 cells were determined by Enzymelinked immunosorbent assay kits and real-time polymerase chain reaction(RT-PCR).RESULTS The rat C6 glioma model was successfully established.High dose lapachol showed significant inhibitory effect on the C6 glioma in Wistar rats(P<0.05).MTS/PMS assay,Hoechst 33258 staining,AnnexinⅤ-FITC/PI staining,and comet assay showed that lapachol could inhibit proliferation,induce apoptosis and DNA damage of C6 cells in dose dependent manners.Lapachol could inhibit the activities of both TOPⅠandⅡ.Molecular docking showed that lapachol-TOPⅠshowed relatively stronger interaction than that of lapachol-TOPⅡ.Enzyme-linked immunosorbent assay and RT-PCR showed that lapachol could inhibit TOPⅡexpression levels,but not TOPⅠexpression levels.CONCLUSION These results showed that lapachol could significantly inhibit C6 glioma both in vivo and in vitro,which might be related with inhibiting TOPⅠand TOPⅡactivities,as wel as TOPⅡexpression.
文摘横波可控震源振动器平板作为页岩气勘探中的关键部件,其疲劳寿命直接影响可控震源的使用寿命和勘探精度。然而,传统的振动器平板疲劳寿命优化方法未考虑平板与平板齿间焊接残余应力的影响,导致平板结构在抗疲劳优化设计方面效果不佳。为此,使用局部灵敏度法对平板疲劳寿命进行敏感性分析,确定了焊接残余应力为影响疲劳寿命的关键因素。随后,建立了平板的各向最大焊接残余应力与焊接速度和焊接层间温度之间的数学模型,并以各向最大焊接残余应力为约束,以疲劳寿命为优化目标,建立相应的优化模型。最后,利用NSGA-Ⅱ(nondominated sorting genetic algorithm-Ⅱ,非支配排序遗传算法-Ⅱ)获取Pareto解集,并结合熵权法和TOPSIS(technique for order preference by similarity to ideal solution,逼近理想解排序)法确定最佳优化方案:焊接速度为10.23 mm/s,焊接层间温度为105℃。结果表明,优化后平板的疲劳寿命为10.23年,相比优化前提高了17.72%。研究结果可为横波可控震源振动器平板的疲劳寿命优化提供科学有效的理论方法和工程指导。
