目的研究白藜芦醇对膜性肾病大鼠的肾保护作用及可能的作用机制。方法将SD大鼠随机分为正常组、模型组及实验组,各20只。用尾静脉注射阳离子化牛血清白蛋白(C-BSA)构建膜性肾病大鼠,正常组给予等量生理盐水。建模后实验组灌胃白藜芦醇(3...目的研究白藜芦醇对膜性肾病大鼠的肾保护作用及可能的作用机制。方法将SD大鼠随机分为正常组、模型组及实验组,各20只。用尾静脉注射阳离子化牛血清白蛋白(C-BSA)构建膜性肾病大鼠,正常组给予等量生理盐水。建模后实验组灌胃白藜芦醇(30 mg·kg-1),模型组及正常组灌胃等量生理盐水,每天1次,连续干预4周。用分光光度计检测24 h尿蛋白定量(UTP),用试剂盒检测血清中肌酸酐(Scr)、尿素氮(BUN)、白蛋白(ALB)、总胆固醇(TC)指标水平,以免疫组化法检测大鼠肾组织synaptopodin蛋白表达情况,以蛋白质印迹(WB)法检测大鼠肾组织中p-Akt、mTOR、PI3K蛋白表达。结果正常组、模型组和实验组大鼠血清中Scr分别为(29.16±1.77),(52.64±2.78)和(40.55±2.65)μmol·L^(-1),BUN分别为(5.86±1.35),(13.54±2.36)和(7.66±3.45)mmol·L^(-1),24 h UTP分别为(6.85±1.26),(39.52±1.24)和(25.36±1.42)mg,ALB分别为(32.15±3.49),(19.63±2.48)和(26.34±2.58)g·L^(-1),TC分别为(1.26±0.52),(4.02±0.36)和(2.36±0.52)mmol·L^(-1),肾组织synaptopodin蛋白表达量分别为(45.36±2.18)%,(12.63±3.85)%,(23.26±3.09)%,差异均有统计学意义(均P<0.05)。模型组肾组织中磷酸化蛋白激酶B(p-Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)、磷脂酰肌醇3-激酶(PI3K)相对表达量较正常组升高,而实验组低于模型组,差异均有统计学意义(均P<0.05)。结论白藜芦醇可减少膜性肾病大鼠尿蛋白程度,防止synaptopodin降解,降低PI3K/Akt/mTOR信号通路中蛋白表达,从而发挥对膜性肾病的肾保护作用。展开更多
The Paris Agreement has prompted much interest in the societal and health impacts of limiting global warming to 1.5 ℃ and 2 ℃. Previous assessments of differential impacts of two targets indicate that 1.5 ℃ warming...The Paris Agreement has prompted much interest in the societal and health impacts of limiting global warming to 1.5 ℃ and 2 ℃. Previous assessments of differential impacts of two targets indicate that 1.5 ℃ warming target would substantially reduce the impact on human health compared to 2 ℃, but they mainly focused on the magnitude of temperature changes under future climate change scenarios without any consideration of greater frequency of cumulative heat exposures within a day. Here we quantified the health risks of compound daytime and nighttime hot extremes using morbidity data in a megacity of China, and also identified the time-period of heat exposure with higher risks. Then we projected future morbidity burden attributable to compound hot extremes due to the half-degree warming. We estimated that the 2 ℃ warming scenario by 2100 as opposed to 1.5 ℃ would increase annual heat-related ambulance dispatches by 31% in Shenzhen city. Substantial additional impacts were associated with occurrence of consecutive hot days and nights, with ambulance dispatches increased by 82%. Our results suggested that compound hot extremes should be considered in assessment of heat-related health impacts, particularly in the context of climate change. Minimizing the warming of climate in a more ambitious target can significantly reduce the health damage.展开更多
文摘目的研究白藜芦醇对膜性肾病大鼠的肾保护作用及可能的作用机制。方法将SD大鼠随机分为正常组、模型组及实验组,各20只。用尾静脉注射阳离子化牛血清白蛋白(C-BSA)构建膜性肾病大鼠,正常组给予等量生理盐水。建模后实验组灌胃白藜芦醇(30 mg·kg-1),模型组及正常组灌胃等量生理盐水,每天1次,连续干预4周。用分光光度计检测24 h尿蛋白定量(UTP),用试剂盒检测血清中肌酸酐(Scr)、尿素氮(BUN)、白蛋白(ALB)、总胆固醇(TC)指标水平,以免疫组化法检测大鼠肾组织synaptopodin蛋白表达情况,以蛋白质印迹(WB)法检测大鼠肾组织中p-Akt、mTOR、PI3K蛋白表达。结果正常组、模型组和实验组大鼠血清中Scr分别为(29.16±1.77),(52.64±2.78)和(40.55±2.65)μmol·L^(-1),BUN分别为(5.86±1.35),(13.54±2.36)和(7.66±3.45)mmol·L^(-1),24 h UTP分别为(6.85±1.26),(39.52±1.24)和(25.36±1.42)mg,ALB分别为(32.15±3.49),(19.63±2.48)和(26.34±2.58)g·L^(-1),TC分别为(1.26±0.52),(4.02±0.36)和(2.36±0.52)mmol·L^(-1),肾组织synaptopodin蛋白表达量分别为(45.36±2.18)%,(12.63±3.85)%,(23.26±3.09)%,差异均有统计学意义(均P<0.05)。模型组肾组织中磷酸化蛋白激酶B(p-Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)、磷脂酰肌醇3-激酶(PI3K)相对表达量较正常组升高,而实验组低于模型组,差异均有统计学意义(均P<0.05)。结论白藜芦醇可减少膜性肾病大鼠尿蛋白程度,防止synaptopodin降解,降低PI3K/Akt/mTOR信号通路中蛋白表达,从而发挥对膜性肾病的肾保护作用。
基金This work was supported by the grant from National Key R&D Program of China(2018YFA0606200).
文摘The Paris Agreement has prompted much interest in the societal and health impacts of limiting global warming to 1.5 ℃ and 2 ℃. Previous assessments of differential impacts of two targets indicate that 1.5 ℃ warming target would substantially reduce the impact on human health compared to 2 ℃, but they mainly focused on the magnitude of temperature changes under future climate change scenarios without any consideration of greater frequency of cumulative heat exposures within a day. Here we quantified the health risks of compound daytime and nighttime hot extremes using morbidity data in a megacity of China, and also identified the time-period of heat exposure with higher risks. Then we projected future morbidity burden attributable to compound hot extremes due to the half-degree warming. We estimated that the 2 ℃ warming scenario by 2100 as opposed to 1.5 ℃ would increase annual heat-related ambulance dispatches by 31% in Shenzhen city. Substantial additional impacts were associated with occurrence of consecutive hot days and nights, with ambulance dispatches increased by 82%. Our results suggested that compound hot extremes should be considered in assessment of heat-related health impacts, particularly in the context of climate change. Minimizing the warming of climate in a more ambitious target can significantly reduce the health damage.