Storm surge inundation is a major concern in marine hazard risk assessment during extreme weather conditions.In this study,a high-resolution coupled model(the ADVanced CIRCulation model+the Simulating WAves Nearshore ...Storm surge inundation is a major concern in marine hazard risk assessment during extreme weather conditions.In this study,a high-resolution coupled model(the ADVanced CIRCulation model+the Simulating WAves Nearshore model)was used to investigate the storm surge inundation in the southwestern Hangzhou Bay region during Typhoon Chan-hom in 2015.The simulated hydrodynamic processes(sea surface wave and storm tide)were validated with measured data from wave buoys and tide gauges,indicating that the overall performance of the model was satisfactory.The storm surge inundation in the coastal area was simulated for several idealized control experiments,including different wave effects(wave-enhanced wind stress,wave-enhanced bottom stress,and wave radiation stress).Dike overflowing cases with different dike heights and dike breaking cases with different dike breach lengths were considered in the simulation.The results highlight the necessity of incorporating wave effects in the accurate simulation of storm surge inundation.Dike height significantly influences the magnitude and phase of the maximum inundation area in the dike overflowing cases,and dike breach length is an important factor impacting the magnitude of the maximum inundation area in the dike breaking cases.This study may serve as a useful reference for accurate coastal inundation simulation and risk assessment.展开更多
目的:探讨加味升降散通过激活线粒体自噬来改善糖尿病肾病(DKD)的作用机制。方法:选取60只7~8周龄的SPF级SD雄性大鼠,采用高糖高脂饮食联合链脲佐菌素(STZ)腹腔注射建立DKD模型,模型建立后随机分为正常组,模型组,加味升降散低、中、高...目的:探讨加味升降散通过激活线粒体自噬来改善糖尿病肾病(DKD)的作用机制。方法:选取60只7~8周龄的SPF级SD雄性大鼠,采用高糖高脂饮食联合链脲佐菌素(STZ)腹腔注射建立DKD模型,模型建立后随机分为正常组,模型组,加味升降散低、中、高剂量组(7.7、15.4、30.8 g·kg^(-1))及厄贝沙坦组(0.384 g·kg^(-1)),每组予以等体积生理盐水和相应浓度药物灌胃,连续给药28 d。检测各组大鼠的血糖、体质量、肾脏质量,通过全自动血液分析仪测定血清中肌酐(SCr)、尿素氮(BUN)含量;酶联免疫吸附测定法(ELISA)测定大鼠尿液中尿微量白蛋白(mALB)、血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的含量;苏木素-伊红(HE)、过碘酸-雪夫(PAS)染色和透射电镜法观察肾脏组织的病理变化;蛋白免疫印迹法(Western blot)测定大鼠肾脏组织线粒体自噬相关蛋白的表达;免疫荧光共定位法检测微管相关蛋白1轻链3β(LC3B)和细胞色素C氧化酶亚基Ⅳ(COXⅣ)的共表达情况。结果:模型组大鼠与正常组比较,肾重指数、血糖及24 h mALB明显升高(P<0.05,P<0.01);SCr、BUN水平均显著升高(P<0.01),血清中的TNF-α、IL-1β和IL-6水平显著上调(P<0.01);大鼠的肾脏组织显示出肾小球肥大、系膜区增宽、系膜区沉积增多、足细胞足突扁平融合,自噬小体数量减少伴随线粒体肿胀,肾小管上皮细胞出现空泡变性,肾间质伴有炎症细胞浸润;肾脏组织中自噬标志蛋白LC3B、PTEN诱导的激酶1(PINK1)、E3泛素蛋白连接酶(Parkin)蛋白表达明显降低(P<0.05,P<0.01),选择性自噬接头蛋白(p62)表达显著增加(P<0.01);免疫荧光信号强度降低、LC3B与COXⅣ的共表达降低。与模型组比较,加味升降散各剂量组和阳性药组大鼠肾重指数、血糖及24 h mALB明显下降(P<0.05,P<0.01);SCr、BUN水平明显下降(P<0.05);血清中的TNF-α、IL-1β和IL-6水平明显降低(P<0.05,P<0.01);肾脏组织肾小球肥大减轻、系膜区沉积减少、足突融合减轻,自噬小体数量增多,线粒体肿胀得到改善;加味升降散各剂量组肾脏中的LC3 B、PINK1、Parkin蛋白表达量明显增加,p62蛋白表达明显减少(P<0.05,P<0.01);免疫荧光信号强度增强,LC3B与COXⅣ的共表达增加。结论:加味升降散通过调节PINK1/Parkin信号通路,激活线粒体自噬,缓解DKD大鼠体内炎症反应,发挥对肾脏的保护作用。展开更多
基金supported by the National Key Research and Development Program of China(Nos.2016YFC140 2000,2016YFC1401002,and 2018YFC1407003)the National Natural Science Foundation of China(NSFC)(NosU1706216,41606024,and 41506023)+3 种基金the CAS(Chinese Academy of Sciences)Strategic Priority Project(No.XDA 19060202)the CAS Innovative Foundation(No.CXJJ-16M111)the NSFC Innovative Group(No.41421005)the NSFC-Shandong Joint Fund for Marine Science Research Centers(No.U1406402)
文摘Storm surge inundation is a major concern in marine hazard risk assessment during extreme weather conditions.In this study,a high-resolution coupled model(the ADVanced CIRCulation model+the Simulating WAves Nearshore model)was used to investigate the storm surge inundation in the southwestern Hangzhou Bay region during Typhoon Chan-hom in 2015.The simulated hydrodynamic processes(sea surface wave and storm tide)were validated with measured data from wave buoys and tide gauges,indicating that the overall performance of the model was satisfactory.The storm surge inundation in the coastal area was simulated for several idealized control experiments,including different wave effects(wave-enhanced wind stress,wave-enhanced bottom stress,and wave radiation stress).Dike overflowing cases with different dike heights and dike breaking cases with different dike breach lengths were considered in the simulation.The results highlight the necessity of incorporating wave effects in the accurate simulation of storm surge inundation.Dike height significantly influences the magnitude and phase of the maximum inundation area in the dike overflowing cases,and dike breach length is an important factor impacting the magnitude of the maximum inundation area in the dike breaking cases.This study may serve as a useful reference for accurate coastal inundation simulation and risk assessment.
文摘目的:探讨加味升降散通过激活线粒体自噬来改善糖尿病肾病(DKD)的作用机制。方法:选取60只7~8周龄的SPF级SD雄性大鼠,采用高糖高脂饮食联合链脲佐菌素(STZ)腹腔注射建立DKD模型,模型建立后随机分为正常组,模型组,加味升降散低、中、高剂量组(7.7、15.4、30.8 g·kg^(-1))及厄贝沙坦组(0.384 g·kg^(-1)),每组予以等体积生理盐水和相应浓度药物灌胃,连续给药28 d。检测各组大鼠的血糖、体质量、肾脏质量,通过全自动血液分析仪测定血清中肌酐(SCr)、尿素氮(BUN)含量;酶联免疫吸附测定法(ELISA)测定大鼠尿液中尿微量白蛋白(mALB)、血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的含量;苏木素-伊红(HE)、过碘酸-雪夫(PAS)染色和透射电镜法观察肾脏组织的病理变化;蛋白免疫印迹法(Western blot)测定大鼠肾脏组织线粒体自噬相关蛋白的表达;免疫荧光共定位法检测微管相关蛋白1轻链3β(LC3B)和细胞色素C氧化酶亚基Ⅳ(COXⅣ)的共表达情况。结果:模型组大鼠与正常组比较,肾重指数、血糖及24 h mALB明显升高(P<0.05,P<0.01);SCr、BUN水平均显著升高(P<0.01),血清中的TNF-α、IL-1β和IL-6水平显著上调(P<0.01);大鼠的肾脏组织显示出肾小球肥大、系膜区增宽、系膜区沉积增多、足细胞足突扁平融合,自噬小体数量减少伴随线粒体肿胀,肾小管上皮细胞出现空泡变性,肾间质伴有炎症细胞浸润;肾脏组织中自噬标志蛋白LC3B、PTEN诱导的激酶1(PINK1)、E3泛素蛋白连接酶(Parkin)蛋白表达明显降低(P<0.05,P<0.01),选择性自噬接头蛋白(p62)表达显著增加(P<0.01);免疫荧光信号强度降低、LC3B与COXⅣ的共表达降低。与模型组比较,加味升降散各剂量组和阳性药组大鼠肾重指数、血糖及24 h mALB明显下降(P<0.05,P<0.01);SCr、BUN水平明显下降(P<0.05);血清中的TNF-α、IL-1β和IL-6水平明显降低(P<0.05,P<0.01);肾脏组织肾小球肥大减轻、系膜区沉积减少、足突融合减轻,自噬小体数量增多,线粒体肿胀得到改善;加味升降散各剂量组肾脏中的LC3 B、PINK1、Parkin蛋白表达量明显增加,p62蛋白表达明显减少(P<0.05,P<0.01);免疫荧光信号强度增强,LC3B与COXⅣ的共表达增加。结论:加味升降散通过调节PINK1/Parkin信号通路,激活线粒体自噬,缓解DKD大鼠体内炎症反应,发挥对肾脏的保护作用。
