目的探讨车前方联合缬沙坦对糖尿病肾病小鼠干预的协同增效作用。方法(1)60只小鼠分为空白对照组(Ctrl,n=10)和造模组(n=50)。Ctrl予普通饲料,造模组小鼠选用高糖高脂饮食(HFD)、单侧肾切除联合腹腔注射链脲佐菌素(STZ)的方法诱导糖尿...目的探讨车前方联合缬沙坦对糖尿病肾病小鼠干预的协同增效作用。方法(1)60只小鼠分为空白对照组(Ctrl,n=10)和造模组(n=50)。Ctrl予普通饲料,造模组小鼠选用高糖高脂饮食(HFD)、单侧肾切除联合腹腔注射链脲佐菌素(STZ)的方法诱导糖尿病肾病模型。空腹血糖≥16.7 mmol·L^(-1)者认定为造模成功,小鼠随机分为模型组(DKD)、缬沙坦组(Val,12 mg·kg^(-1))、车前方组(CQF,2.1 g·kg^(-1)生药)和车前方联合缬沙坦组(CV,Val 12 mg·kg^(-1)+CQF 2.1 g·kg^(-1)生药),每组10只,连续给药干预12周。定期测量各组体质量、日饮水量、尿量;采用胰岛素耐量实验(ITT)以及空腹血糖(FBG)评估糖代谢功能;采用血尿素氮(BUN)、内生肌酐清除率(CCr)、24 h尿蛋白(UP)、24 h尿肌酐(Cr)、24 h尿中肾损伤分子-1(KIM-1)与中性粒细胞明胶酶相关脂质运载蛋白(NGAL)排泄量等指标评估肾功能;采用苏木精-伊红(HE)、马松(Masson)、过典酸雪夫氏(PAS)染色观察肾脏组织病理变化;分析肾小球超微结构变化。(2)基于超高效液相色谱-质谱联用(UPLC-MS/MS)方法测定正常小鼠单次灌胃缬沙坦(12 mg·kg^(-1))、车前方(生药2.1 g·kg^(-1))与联合给药的药代动力学指标,选择非房室模型方法计算药代动力学参数。结果(1)与Ctrl比较,DKD小鼠体质量明显下降,饮水量、尿量、FBG、ITT-葡萄糖曲线下面积(ITT-AUCG)、CCr、BUN、24 h UP、24 h Cr、24 h KIM-1、24 h NGAL水平异常升高;与DKD比较,各给药干预组饮水量、尿量、糖代谢及肾功能部分指标明显下降(P<0.05)。与Ctrl比较,DKD肾小球肥大、系膜区增宽,肾小管出现上皮细胞肿胀、小空泡样变性(P<0.05),肾小球窗孔消失,足突融合增宽,基底膜均质性增厚;与DKD比较,给药干预组肾脏形态与肾小球超微结构明显逆转(P<0.05)。各给药干预组组间比较,与Val相较,CV的CCr、24 h KIM-1、24 h NGAL排泄率下降更为显著(P<0.05);与CQF比较,CV的FBG、UACR值改善更为显著(P<0.05)。(2)与单药(缬沙坦或车前方)干预比较,联合给药(车前方联合缬沙坦)可增加缬沙坦血药浓度(提高1.59倍,P<0.05);促进车前方中主要活性成分小檗碱(BBR)、黄连碱(COP)、木兰花碱(MAG)和京尼平苷酸(GPA)的吸收(血药浓度时间曲线下面积0-t分别提高37.54%、36.05%、85.80%、26.11%,P<0.05)。结论车前方联合缬沙坦可提高活性成分的生物利用度,从而有效改善糖尿病肾病的糖代谢紊乱和肾功能损伤,发挥协同增效作用。展开更多
Train control systems ensure the safety of railways. This paper begins with a summary of the typical train control systems in Japan and Europe. Based on this summary, the author then raises the following question rega...Train control systems ensure the safety of railways. This paper begins with a summary of the typical train control systems in Japan and Europe. Based on this summary, the author then raises the following question regarding current train control systems： What approach should be adopted in order to enhance the functionality, safety, and reliability of train control systems and assist in commercial operations on railways？ Next, the author provides a desirable architecture that is likely to assist with the development of new train control systems based on current information and communication technologies. A new unified train control system （UTCS） is proposed that is effective in enhancing the robustness and com- petitiveness of a train control system. The ultimate architecture of the UTCS will be only composed of essential elements such as point machines and level crossing control devices in the field. Finally, a pro- cessing method of the UTCS is discussed.展开更多
文摘目的探讨车前方联合缬沙坦对糖尿病肾病小鼠干预的协同增效作用。方法(1)60只小鼠分为空白对照组(Ctrl,n=10)和造模组(n=50)。Ctrl予普通饲料,造模组小鼠选用高糖高脂饮食(HFD)、单侧肾切除联合腹腔注射链脲佐菌素(STZ)的方法诱导糖尿病肾病模型。空腹血糖≥16.7 mmol·L^(-1)者认定为造模成功,小鼠随机分为模型组(DKD)、缬沙坦组(Val,12 mg·kg^(-1))、车前方组(CQF,2.1 g·kg^(-1)生药)和车前方联合缬沙坦组(CV,Val 12 mg·kg^(-1)+CQF 2.1 g·kg^(-1)生药),每组10只,连续给药干预12周。定期测量各组体质量、日饮水量、尿量;采用胰岛素耐量实验(ITT)以及空腹血糖(FBG)评估糖代谢功能;采用血尿素氮(BUN)、内生肌酐清除率(CCr)、24 h尿蛋白(UP)、24 h尿肌酐(Cr)、24 h尿中肾损伤分子-1(KIM-1)与中性粒细胞明胶酶相关脂质运载蛋白(NGAL)排泄量等指标评估肾功能;采用苏木精-伊红(HE)、马松(Masson)、过典酸雪夫氏(PAS)染色观察肾脏组织病理变化;分析肾小球超微结构变化。(2)基于超高效液相色谱-质谱联用(UPLC-MS/MS)方法测定正常小鼠单次灌胃缬沙坦(12 mg·kg^(-1))、车前方(生药2.1 g·kg^(-1))与联合给药的药代动力学指标,选择非房室模型方法计算药代动力学参数。结果(1)与Ctrl比较,DKD小鼠体质量明显下降,饮水量、尿量、FBG、ITT-葡萄糖曲线下面积(ITT-AUCG)、CCr、BUN、24 h UP、24 h Cr、24 h KIM-1、24 h NGAL水平异常升高;与DKD比较,各给药干预组饮水量、尿量、糖代谢及肾功能部分指标明显下降(P<0.05)。与Ctrl比较,DKD肾小球肥大、系膜区增宽,肾小管出现上皮细胞肿胀、小空泡样变性(P<0.05),肾小球窗孔消失,足突融合增宽,基底膜均质性增厚;与DKD比较,给药干预组肾脏形态与肾小球超微结构明显逆转(P<0.05)。各给药干预组组间比较,与Val相较,CV的CCr、24 h KIM-1、24 h NGAL排泄率下降更为显著(P<0.05);与CQF比较,CV的FBG、UACR值改善更为显著(P<0.05)。(2)与单药(缬沙坦或车前方)干预比较,联合给药(车前方联合缬沙坦)可增加缬沙坦血药浓度(提高1.59倍,P<0.05);促进车前方中主要活性成分小檗碱(BBR)、黄连碱(COP)、木兰花碱(MAG)和京尼平苷酸(GPA)的吸收(血药浓度时间曲线下面积0-t分别提高37.54%、36.05%、85.80%、26.11%,P<0.05)。结论车前方联合缬沙坦可提高活性成分的生物利用度,从而有效改善糖尿病肾病的糖代谢紊乱和肾功能损伤,发挥协同增效作用。
文摘Train control systems ensure the safety of railways. This paper begins with a summary of the typical train control systems in Japan and Europe. Based on this summary, the author then raises the following question regarding current train control systems： What approach should be adopted in order to enhance the functionality, safety, and reliability of train control systems and assist in commercial operations on railways？ Next, the author provides a desirable architecture that is likely to assist with the development of new train control systems based on current information and communication technologies. A new unified train control system （UTCS） is proposed that is effective in enhancing the robustness and com- petitiveness of a train control system. The ultimate architecture of the UTCS will be only composed of essential elements such as point machines and level crossing control devices in the field. Finally, a pro- cessing method of the UTCS is discussed.
