Background:Ischemic stroke is characterized by permanent or transient obstruction of blood flow,leading to a growing risk factor and health burden.Tianmagouteng yin(TMG)is commonly used in Chinese medicine to treat ce...Background:Ischemic stroke is characterized by permanent or transient obstruction of blood flow,leading to a growing risk factor and health burden.Tianmagouteng yin(TMG)is commonly used in Chinese medicine to treat cerebral ischemia.The aim of this study was to investigate the neuroprotective effects of TMG against ischemic stroke.Methods:Either permanent middle cerebral artery occlusion(pMCAO)or sham operation was performed on anesthetized Wistar male rats(n=36).Results:Results demonstrated that TMG administration reduced the infarction volume and mitigated the neurobehavioral deficits.Hematoxylin and eosin(HE)staining and Prussian blue staining revealed that TMG attenuated tissue disruption and microbleeds in hippocampus tissues.In addition,TMG down-regulated the receptor of advanced glycation end products(RAGE)and p-JAK2.It also inhibited the concentrations of advanced glycation end products(AGEs),ferritin,malondialdehyde(MDA),and reactive oxygen species(ROS).Conclusion:As repetitive clinical trials of neuroprotectants targeting stroke have failed previously,our results suggested that the natural product,TMG,can probably help in the vicious cycles of ischemic stroke pathology.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
The aim of this study was to investigate the effects of high-advanced glycation end products(AGEs) diet on diabetic vascular complications. The Streptozocin(STZ)-induced diabetic mice were fed with high-AGEs diet. Dia...The aim of this study was to investigate the effects of high-advanced glycation end products(AGEs) diet on diabetic vascular complications. The Streptozocin(STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia,polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein(CRP), low density lipoprotein(LDL), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species(ROS) and low-levels of superoxide dismutase(SOD) in serum, heart, and kidneys. It also upregulated RAGE mR NA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.展开更多
基金Zhejiang TCM Science and Technology Program[Grant Number 2021ZA050].
文摘Background:Ischemic stroke is characterized by permanent or transient obstruction of blood flow,leading to a growing risk factor and health burden.Tianmagouteng yin(TMG)is commonly used in Chinese medicine to treat cerebral ischemia.The aim of this study was to investigate the neuroprotective effects of TMG against ischemic stroke.Methods:Either permanent middle cerebral artery occlusion(pMCAO)or sham operation was performed on anesthetized Wistar male rats(n=36).Results:Results demonstrated that TMG administration reduced the infarction volume and mitigated the neurobehavioral deficits.Hematoxylin and eosin(HE)staining and Prussian blue staining revealed that TMG attenuated tissue disruption and microbleeds in hippocampus tissues.In addition,TMG down-regulated the receptor of advanced glycation end products(RAGE)and p-JAK2.It also inhibited the concentrations of advanced glycation end products(AGEs),ferritin,malondialdehyde(MDA),and reactive oxygen species(ROS).Conclusion:As repetitive clinical trials of neuroprotectants targeting stroke have failed previously,our results suggested that the natural product,TMG,can probably help in the vicious cycles of ischemic stroke pathology.
基金Scientific Research Project of Hebei Administration of Traditional Chinese Medicine(2020136)Science Research Project of Hebei Education Department(ZD2022043)。
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supported by National Nature Science Foundation of China(No.81073111)the Priority Academic Program Development of Jiangsu Higher Education Institutions(No.nzyzyxjp1006)Jiangsu Province graduate student scientific research innovation plan project(No.CXZZ13_0622)
文摘The aim of this study was to investigate the effects of high-advanced glycation end products(AGEs) diet on diabetic vascular complications. The Streptozocin(STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia,polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein(CRP), low density lipoprotein(LDL), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species(ROS) and low-levels of superoxide dismutase(SOD) in serum, heart, and kidneys. It also upregulated RAGE mR NA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.
