糖尿病血管并发症是糖尿病患者死亡的主要原因之一，许多研究旨在探索其病因以及发生发展的机制。近年来，关于晚期糖基化终末产物（advanced glycation end products，AGEs）及其受体（receptor for advanced glycation end products，...糖尿病血管并发症是糖尿病患者死亡的主要原因之一，许多研究旨在探索其病因以及发生发展的机制。近年来，关于晚期糖基化终末产物（advanced glycation end products，AGEs）及其受体（receptor for advanced glycation end products，RAGE）系统对糖尿病血管损伤影响的研究较为深入，笔者选取其中具有重要意义的几个方面做简要说明，醚AGEs／AGE—RAGE系统如何影响糖尿病血管并发症的转归，探讨目前针对AGEs／AGE—RAGE治疗上的一些最新进展.展开更多
目的探讨可溶性RAGE(soluble form of receptor for advanced glycation-end products,sRAGE)对晚期糖基化终产物(advanced glycation end products,AGEs)-晚期糖基化终产物受体(receptor for advanced glycation-end products,RAGE)介...目的探讨可溶性RAGE(soluble form of receptor for advanced glycation-end products,sRAGE)对晚期糖基化终产物(advanced glycation end products,AGEs)-晚期糖基化终产物受体(receptor for advanced glycation-end products,RAGE)介导的C57BL/6J小鼠SGCs(spiral ganglion cells,SGCs)凋亡及RAGE受体表达的影响。方法不同浓度的sRAGE作用于培养5天后的螺旋神经节细胞和加入AGEs-BSA作用2 h后的SGCs细胞,采用免疫荧光法鉴定SGCs,通过流式细胞术检测细胞凋亡,以及RT-PCR检测RAGE的mRNA的表达,琼脂糖凝胶电泳对扩增结果进行确认,同时采用western blot技术检测凋亡相关蛋白Bax、BCL-2及caspase-3的表达情况。结果原代培养获得足够数量以及活性良好的SGCs,并用小鼠抗神经微丝蛋白抗体染色以鉴定。单纯向SGCs加入不同浓度的sRAGE,细胞凋亡无明显增加,RAGE受体的表达无明显增多;而不同浓度sRAGE加入AGEs作用的SGCs后,可见SGCs的凋亡随sRAGE浓度增加而减少,呈浓度相关性,RAGE受体的mRNA表达也随之减弱。凋亡相关蛋白中,BCL-2表达升高,Bax及cleaved caspase-3表达降低。结论 s RAGE可以减少AGEs诱导的SGCs的凋亡,并减少膜上RAGE受体的表达,可能与s RAGE竞争性结合AGEs而不产生相应生物学效应有关。展开更多
目的:观察小檗碱对糖尿病认知功能障碍模型小鼠AGEs/RAGE/NF-κB信号通路的作用,并探讨小檗碱缓解糖尿病认知功能障碍的相关机制。方法:将实验小鼠随机分为空白组,模型组,小檗碱低、中、高剂量组,除空白组外,其他各组制备糖尿病认知功...目的:观察小檗碱对糖尿病认知功能障碍模型小鼠AGEs/RAGE/NF-κB信号通路的作用,并探讨小檗碱缓解糖尿病认知功能障碍的相关机制。方法:将实验小鼠随机分为空白组,模型组,小檗碱低、中、高剂量组,除空白组外,其他各组制备糖尿病认知功能障碍模型。造模成功后小檗碱低、中、高剂量组分别给予不同剂量的小檗碱,空白组和模型组给予等体积的生理盐水。Morris水迷宫检测小鼠的学习记忆能力,尼氏染色观察小鼠海马病理形态变化,ELISA检测小鼠血清中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白细胞介素1β(interleukin-1β,IL-1β)的表达,Real time-PCR和Western bolt检测海马中晚期糖基化终末产物(advanced glycation end products,AGEs)、晚期糖蛋白终末产物受体(receptor for advanced glycation end products,RAGE)、核因子κB(nuclear factor-κB,NF-κB)的基因和蛋白表达水平。结果:与空白组比较,模型组小鼠上平台潜伏期、游泳总路程和第1次抵原平台时间明显增加(P<0.01),穿越平台次数、目标象限时间则明显减少(P<0.01)。与模型组相比,小檗碱高剂量组小鼠上平台潜伏期、游泳总路程和第1次抵原平台时间均有不同程度减少(P<0.05),穿越平台次数、目标象限时间则有不同程度增加(P<0.05)。空白组小鼠海马CA3区神经元排列均匀整齐,细胞核饱满,尼氏体染色均匀,大小均一。模型组小鼠海马CA3区神经元减少,尼氏体固缩、深染。小檗碱高剂量组神经元恢复较好,排列较整齐,尼氏体固缩、深染明显好转。与空白组相比,模型组小鼠血清中TNF-α、IL-1β表达水平及海马中AGEs、RAGE、NF-κB的mRNA和蛋白表达水平均升高(P<0.05),与模型组相比,小檗碱高剂量组小鼠血清中TNF-α、IL-1β水平及海马中AGEs、RAGE、NF-κB的mRNA和蛋白表达均下降(P<0.05)。结论:小檗碱能缓解糖尿病认知功能障碍模型小鼠的记忆缺陷,其机制可能与其下调AGEs/RAGE/NF-κB信号通路有关。展开更多
机体衰老以皮肤的衰老最为直观。成纤维细胞是真皮中最重要的细胞成分,其在皮肤老化的过程中扮演着重要角色。当皮肤衰老时,成纤维细胞出现不可逆生长抑制、分泌及合成功能下降、细胞自身修复能力降低等一系列改变。随着人们生活水平的...机体衰老以皮肤的衰老最为直观。成纤维细胞是真皮中最重要的细胞成分,其在皮肤老化的过程中扮演着重要角色。当皮肤衰老时,成纤维细胞出现不可逆生长抑制、分泌及合成功能下降、细胞自身修复能力降低等一系列改变。随着人们生活水平的提高,西式饮食普遍化及烹饪方式多样化使得人体摄入过量的葡萄糖,从而导致非酶糖化反应(nonenzymic glycation,NEG)的增加,最终使得晚期糖基化终末产物(advanced glycation end products,AGEs)的升高。目前有研究表明AGEs可直接或与其特定受体(receptor for advanced glycation end products,RAGE)相互作用加速皮肤成纤维细胞衰老。近年来,AGEs与皮肤衰老关系成为人们研究的热点,该文就此进行综述。展开更多
This study aimed to investigate whether pitavastatin protected against injury induced by advanced glycation end products products（AGEs） in neonatal rat cardiomyocytes,and to examine the underlying mechanisms.Cardiom...This study aimed to investigate whether pitavastatin protected against injury induced by advanced glycation end products products（AGEs） in neonatal rat cardiomyocytes,and to examine the underlying mechanisms.Cardiomyocytes of neonatal rats were incubated for 48 hours with AGEs（100 μg/mL）,receptor for advanced glycation end products（RAGE）,antibody（1 μg/mL） and pitavastatin（600 ng/mL）.The levels of p62 and beclinl were determined by Western blotting.Mitochondrial membrane potential（△Ψm） and the generation of reactive oxygen species（ROS） were measured through the JC-1 and DCFH-DA.In the AGEs group,the expression of beclinl was remarkably increased compared to the control group,while the expression of p62 was significantly decreased.AGEs also markedly decreased △Ψm and significantly increased ROS compared with the control group.After treatment with RAGE antibody or pitavastatin,the level of beclinl was markedly decreased compared with the AGEs group,but the level of p62 was remarkably increased.In the AGEs ＋ RAGE antibody group and AGEs＋ pitavastatin group,△Ψm was significantly increased and ROS was remarkably decreased compared with the AGEs group.In conclusion,AGEs-RAGE may induce autophagy of cardiomyocytes by generation of ROS and pitavastatin could protect against AGEs-induced injury against cardiomyocytes.展开更多
文摘糖尿病血管并发症是糖尿病患者死亡的主要原因之一，许多研究旨在探索其病因以及发生发展的机制。近年来，关于晚期糖基化终末产物（advanced glycation end products，AGEs）及其受体（receptor for advanced glycation end products，RAGE）系统对糖尿病血管损伤影响的研究较为深入，笔者选取其中具有重要意义的几个方面做简要说明，醚AGEs／AGE—RAGE系统如何影响糖尿病血管并发症的转归，探讨目前针对AGEs／AGE—RAGE治疗上的一些最新进展.
文摘目的探讨可溶性RAGE(soluble form of receptor for advanced glycation-end products,sRAGE)对晚期糖基化终产物(advanced glycation end products,AGEs)-晚期糖基化终产物受体(receptor for advanced glycation-end products,RAGE)介导的C57BL/6J小鼠SGCs(spiral ganglion cells,SGCs)凋亡及RAGE受体表达的影响。方法不同浓度的sRAGE作用于培养5天后的螺旋神经节细胞和加入AGEs-BSA作用2 h后的SGCs细胞,采用免疫荧光法鉴定SGCs,通过流式细胞术检测细胞凋亡,以及RT-PCR检测RAGE的mRNA的表达,琼脂糖凝胶电泳对扩增结果进行确认,同时采用western blot技术检测凋亡相关蛋白Bax、BCL-2及caspase-3的表达情况。结果原代培养获得足够数量以及活性良好的SGCs,并用小鼠抗神经微丝蛋白抗体染色以鉴定。单纯向SGCs加入不同浓度的sRAGE,细胞凋亡无明显增加,RAGE受体的表达无明显增多;而不同浓度sRAGE加入AGEs作用的SGCs后,可见SGCs的凋亡随sRAGE浓度增加而减少,呈浓度相关性,RAGE受体的mRNA表达也随之减弱。凋亡相关蛋白中,BCL-2表达升高,Bax及cleaved caspase-3表达降低。结论 s RAGE可以减少AGEs诱导的SGCs的凋亡,并减少膜上RAGE受体的表达,可能与s RAGE竞争性结合AGEs而不产生相应生物学效应有关。
文摘目的:观察小檗碱对糖尿病认知功能障碍模型小鼠AGEs/RAGE/NF-κB信号通路的作用,并探讨小檗碱缓解糖尿病认知功能障碍的相关机制。方法:将实验小鼠随机分为空白组,模型组,小檗碱低、中、高剂量组,除空白组外,其他各组制备糖尿病认知功能障碍模型。造模成功后小檗碱低、中、高剂量组分别给予不同剂量的小檗碱,空白组和模型组给予等体积的生理盐水。Morris水迷宫检测小鼠的学习记忆能力,尼氏染色观察小鼠海马病理形态变化,ELISA检测小鼠血清中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白细胞介素1β(interleukin-1β,IL-1β)的表达,Real time-PCR和Western bolt检测海马中晚期糖基化终末产物(advanced glycation end products,AGEs)、晚期糖蛋白终末产物受体(receptor for advanced glycation end products,RAGE)、核因子κB(nuclear factor-κB,NF-κB)的基因和蛋白表达水平。结果:与空白组比较,模型组小鼠上平台潜伏期、游泳总路程和第1次抵原平台时间明显增加(P<0.01),穿越平台次数、目标象限时间则明显减少(P<0.01)。与模型组相比,小檗碱高剂量组小鼠上平台潜伏期、游泳总路程和第1次抵原平台时间均有不同程度减少(P<0.05),穿越平台次数、目标象限时间则有不同程度增加(P<0.05)。空白组小鼠海马CA3区神经元排列均匀整齐,细胞核饱满,尼氏体染色均匀,大小均一。模型组小鼠海马CA3区神经元减少,尼氏体固缩、深染。小檗碱高剂量组神经元恢复较好,排列较整齐,尼氏体固缩、深染明显好转。与空白组相比,模型组小鼠血清中TNF-α、IL-1β表达水平及海马中AGEs、RAGE、NF-κB的mRNA和蛋白表达水平均升高(P<0.05),与模型组相比,小檗碱高剂量组小鼠血清中TNF-α、IL-1β水平及海马中AGEs、RAGE、NF-κB的mRNA和蛋白表达均下降(P<0.05)。结论:小檗碱能缓解糖尿病认知功能障碍模型小鼠的记忆缺陷,其机制可能与其下调AGEs/RAGE/NF-κB信号通路有关。
基金Scientific Research Project of Hebei Administration of Traditional Chinese Medicine(2020136)Science Research Project of Hebei Education Department(ZD2022043)。
文摘机体衰老以皮肤的衰老最为直观。成纤维细胞是真皮中最重要的细胞成分,其在皮肤老化的过程中扮演着重要角色。当皮肤衰老时,成纤维细胞出现不可逆生长抑制、分泌及合成功能下降、细胞自身修复能力降低等一系列改变。随着人们生活水平的提高,西式饮食普遍化及烹饪方式多样化使得人体摄入过量的葡萄糖,从而导致非酶糖化反应(nonenzymic glycation,NEG)的增加,最终使得晚期糖基化终末产物(advanced glycation end products,AGEs)的升高。目前有研究表明AGEs可直接或与其特定受体(receptor for advanced glycation end products,RAGE)相互作用加速皮肤成纤维细胞衰老。近年来,AGEs与皮肤衰老关系成为人们研究的热点,该文就此进行综述。
基金supported by the National NaturalScience Foundation of China(NSFC 81570328,Wang Junhong)the"Sixth-Peak Talent"of Jiangsu Province(2011WSN-029 to Prof.Guo Yan and2013WSN-036 to Dr.Wang Junhong)support by the Health Department of Jiangsu Province(z201301)
文摘This study aimed to investigate whether pitavastatin protected against injury induced by advanced glycation end products products（AGEs） in neonatal rat cardiomyocytes,and to examine the underlying mechanisms.Cardiomyocytes of neonatal rats were incubated for 48 hours with AGEs（100 μg/mL）,receptor for advanced glycation end products（RAGE）,antibody（1 μg/mL） and pitavastatin（600 ng/mL）.The levels of p62 and beclinl were determined by Western blotting.Mitochondrial membrane potential（△Ψm） and the generation of reactive oxygen species（ROS） were measured through the JC-1 and DCFH-DA.In the AGEs group,the expression of beclinl was remarkably increased compared to the control group,while the expression of p62 was significantly decreased.AGEs also markedly decreased △Ψm and significantly increased ROS compared with the control group.After treatment with RAGE antibody or pitavastatin,the level of beclinl was markedly decreased compared with the AGEs group,but the level of p62 was remarkably increased.In the AGEs ＋ RAGE antibody group and AGEs＋ pitavastatin group,△Ψm was significantly increased and ROS was remarkably decreased compared with the AGEs group.In conclusion,AGEs-RAGE may induce autophagy of cardiomyocytes by generation of ROS and pitavastatin could protect against AGEs-induced injury against cardiomyocytes.
