多囊卵巢综合征(Polycystic ovary syndrome,PCOS)是一组生殖内分泌代谢紊乱的综合征,临床以稀发排卵、高雄激素体征、胰岛素抵抗为主要特征,其中育龄期发病率高,对女性生育力造成严重不良影响。PCOS的发生发展涉及多种信号通路,腺苷酸...多囊卵巢综合征(Polycystic ovary syndrome,PCOS)是一组生殖内分泌代谢紊乱的综合征,临床以稀发排卵、高雄激素体征、胰岛素抵抗为主要特征,其中育龄期发病率高,对女性生育力造成严重不良影响。PCOS的发生发展涉及多种信号通路,腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)及哺乳动物雷帕霉素靶蛋白(Mammalian target of rapamycin,mTOR)作为细胞能量感受器是其中两个关键靶点。二者在PCOS各个发病部位包括下丘脑-垂体-卵巢轴、子宫内膜、脂肪与骨骼肌中发挥重要的调节作用,通过影响细胞自噬、氧化应激、炎症、线粒体功能、葡萄糖摄取等,促进卵泡的发育和成熟,改善胰岛素抵抗。近年来,中医药因其成分多样、靶点众多等优势广泛应用于临床,研究人员已对PCOS的发病以及中药治疗及改善PCOS的机制进行了大量研究,结果提示AMPK与mTOR相关通路在其中发挥关键作用。通过总结中药干预AMPK与mTOR及其相关通路治疗PCOS的研究结果,为临床治疗及基础研究提供参考。展开更多
Background:Metabolic stress has been proposed to contribute to neuronal damage in glaucoma,but the mechanism driving this response is not understood.The adenosine monophosphate-activated protein kinase(AMPK)is a maste...Background:Metabolic stress has been proposed to contribute to neuronal damage in glaucoma,but the mechanism driving this response is not understood.The adenosine monophosphate-activated protein kinase(AMPK)is a master regulator of energy homeostasis that becomes active at the onset of energy stress.AMPK is a potent inhibitor of the mammalian target of rapamycin complex 1(mTORC1),which we showed is essential for the maintenance of retinal ganglion cell(RGC)dendrites,synapses,and survival.Here,we tested the hypothesis that AMPK is an early mediator of metabolic stress in glaucoma.Methods:Unilateral elevation of intraocular pressure was induced by injection of magnetic microbeads into the anterior chamber of mice expressing yellow fluorescent protein in RGCs.Inhibition of AMPK was achieved by administration of siRNA or compound C.RGC dendritic trees were 3D-reconstructed and analyzed with Imaris(Bitplane),and survival was assessed by counting Brn3a or RBPMS-labeled soma and axons in the optic nerve.RGC function was examined by quantification of anterograde axonal transport after intraocular administration of cholera toxinβ-subunit.Retinas from glaucoma patients were analyzed for expression of active AMPK.Results:Ocular hypertension triggered rapid upregulation of AMPK activity in RGCs concomitant with loss of mTORC1 function.AMPK inhibition with compound C or siRNA effectively restored mTORC1 activity and promoted an increase in total dendritic length,surface and complexity relative to control retinas.Attenuation of AMPK activity led to robust RGC soma and axon survival.For example,95%of RGCs(2,983±258 RGCs/mm2,mean±S.E.M.)survived with compound C compared to 77%in vehicle-treated eyes(2,430±233 RGCs/mm2)(ANOVA,P<0.001)at three weeks after glaucoma induction(n=8-10/group).Importantly,blockade of AMPK activity effectively restored anterograde axonal transport.Lastly,RGC-specific upregulation of AMPK activity was detected in human glaucomatous retinas relative to age-matched controls(n=10/group).Conclusions:Metabolic stress in glaucoma involves AMPK activation and mTORC1 inhibition promoting early RGC dendritic pathology,dysfunction and neurodegeneration.展开更多
【目的】探讨黄芪甲苷对糖尿病肾病大鼠的治疗作用及机制。【方法】将27只大鼠随机分为正常组、模型组、黄芪甲苷组,每组9只。模型组、黄芪甲苷组大鼠给予高脂饲料喂养联合链脲佐菌素(STZ)40 mg/kg腹腔注射构建2型糖尿病肾病模型。造模...【目的】探讨黄芪甲苷对糖尿病肾病大鼠的治疗作用及机制。【方法】将27只大鼠随机分为正常组、模型组、黄芪甲苷组,每组9只。模型组、黄芪甲苷组大鼠给予高脂饲料喂养联合链脲佐菌素(STZ)40 mg/kg腹腔注射构建2型糖尿病肾病模型。造模成功后,黄芪甲苷组给予黄芪甲苷40 mg/kg灌胃治疗,正常组、模型组给予等体积生理盐水,每日1次,持续12周。12周后,测定大鼠空腹血糖(FBG)、尿白蛋白/尿肌酐比值(UACR)、血尿素氮(BUN)、血清肌酐(SCr)水平;苏木素-伊红(HE)染色法观察肾脏病理结构变化;过碘酸雪夫(PAS)染色、马松(Masson)染色法观察肾脏纤维化程度;定量聚合酶链反应(qPCR)、蛋白免疫印迹(Western Blot)法检测肾脏组织中腺苷酸蛋白活化激酶(AMPK)、内皮型一氧化氮合酶(e NOS)mRNA及蛋白表达水平。【结果】与模型组比较,黄芪甲苷组大鼠FBG、UACR显著降低(P<0.05),BUN、SCr含量未见明显改变;与模型组比较,黄芪甲苷组大鼠肾小球体积减小,基底膜增厚、系膜基质增生、肾小囊腔狭窄程度、胶原纤维沉积明显减轻;进一步的实验结果显示,黄芪甲苷组肾脏组织中AMPK、e NOS m RNA表达水平较模型组明显升高(P<0.05),AMPK的磷酸化水平及eNOS蛋白表达水平较模型组明显上调(P<0.05)。【结论】黄芪甲苷可改善大鼠糖尿病肾损害,其机制可能与激活AMPK/eNOS信号通路有关。展开更多
背景:近年来,有研究发现部分中药单体通过激活细胞自噬可缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,防治皮瓣坏死。目的:综述中药单体调控细胞自噬防治皮瓣坏死的研究进展。方法:分别以“中药、细胞自噬、皮瓣”与“Traditional Chi...背景:近年来,有研究发现部分中药单体通过激活细胞自噬可缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,防治皮瓣坏死。目的:综述中药单体调控细胞自噬防治皮瓣坏死的研究进展。方法:分别以“中药、细胞自噬、皮瓣”与“Traditional Chinese Medicine (TCM),Autophagy,Skin flaps”为中英文检索词,由第一作者检索2010年1月至2022年10月发表在中国知网与PubMed数据库的相关文献,文献初筛共检索到相关文献196篇,以纳入和排除标准进行筛选,通过阅读文献标题与摘要进行质量评估,最终归纳整理55篇文献进行综述。结果与结论:(1)细胞自噬的调控是由AMPK/mTOR和PI3K/AKT等信号通路介导的,激活细胞自噬可缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,防治皮瓣坏死。(2)中药单体中的萜类化合物(桦木酸、穿心莲内酯、三七三萜和梓醇)、酚类化合物(白藜芦醇、姜黄素和天麻素)、酚酸类化合物(丹酚酸B)及类固醇类化合物(拟人参皂甙F11)可通过调控相关信号通路激活细胞自噬来缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,促皮瓣存活。(3)文章通过总结中药单体调控细胞自噬防治皮瓣坏死的研究进展,为临床上中药防治皮瓣坏死、促进皮瓣愈合提供参考与理论依据。展开更多
文摘多囊卵巢综合征(Polycystic ovary syndrome,PCOS)是一组生殖内分泌代谢紊乱的综合征,临床以稀发排卵、高雄激素体征、胰岛素抵抗为主要特征,其中育龄期发病率高,对女性生育力造成严重不良影响。PCOS的发生发展涉及多种信号通路,腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)及哺乳动物雷帕霉素靶蛋白(Mammalian target of rapamycin,mTOR)作为细胞能量感受器是其中两个关键靶点。二者在PCOS各个发病部位包括下丘脑-垂体-卵巢轴、子宫内膜、脂肪与骨骼肌中发挥重要的调节作用,通过影响细胞自噬、氧化应激、炎症、线粒体功能、葡萄糖摄取等,促进卵泡的发育和成熟,改善胰岛素抵抗。近年来,中医药因其成分多样、靶点众多等优势广泛应用于临床,研究人员已对PCOS的发病以及中药治疗及改善PCOS的机制进行了大量研究,结果提示AMPK与mTOR相关通路在其中发挥关键作用。通过总结中药干预AMPK与mTOR及其相关通路治疗PCOS的研究结果,为临床治疗及基础研究提供参考。
文摘Background:Metabolic stress has been proposed to contribute to neuronal damage in glaucoma,but the mechanism driving this response is not understood.The adenosine monophosphate-activated protein kinase(AMPK)is a master regulator of energy homeostasis that becomes active at the onset of energy stress.AMPK is a potent inhibitor of the mammalian target of rapamycin complex 1(mTORC1),which we showed is essential for the maintenance of retinal ganglion cell(RGC)dendrites,synapses,and survival.Here,we tested the hypothesis that AMPK is an early mediator of metabolic stress in glaucoma.Methods:Unilateral elevation of intraocular pressure was induced by injection of magnetic microbeads into the anterior chamber of mice expressing yellow fluorescent protein in RGCs.Inhibition of AMPK was achieved by administration of siRNA or compound C.RGC dendritic trees were 3D-reconstructed and analyzed with Imaris(Bitplane),and survival was assessed by counting Brn3a or RBPMS-labeled soma and axons in the optic nerve.RGC function was examined by quantification of anterograde axonal transport after intraocular administration of cholera toxinβ-subunit.Retinas from glaucoma patients were analyzed for expression of active AMPK.Results:Ocular hypertension triggered rapid upregulation of AMPK activity in RGCs concomitant with loss of mTORC1 function.AMPK inhibition with compound C or siRNA effectively restored mTORC1 activity and promoted an increase in total dendritic length,surface and complexity relative to control retinas.Attenuation of AMPK activity led to robust RGC soma and axon survival.For example,95%of RGCs(2,983±258 RGCs/mm2,mean±S.E.M.)survived with compound C compared to 77%in vehicle-treated eyes(2,430±233 RGCs/mm2)(ANOVA,P<0.001)at three weeks after glaucoma induction(n=8-10/group).Importantly,blockade of AMPK activity effectively restored anterograde axonal transport.Lastly,RGC-specific upregulation of AMPK activity was detected in human glaucomatous retinas relative to age-matched controls(n=10/group).Conclusions:Metabolic stress in glaucoma involves AMPK activation and mTORC1 inhibition promoting early RGC dendritic pathology,dysfunction and neurodegeneration.
文摘【目的】探讨黄芪甲苷对糖尿病肾病大鼠的治疗作用及机制。【方法】将27只大鼠随机分为正常组、模型组、黄芪甲苷组,每组9只。模型组、黄芪甲苷组大鼠给予高脂饲料喂养联合链脲佐菌素(STZ)40 mg/kg腹腔注射构建2型糖尿病肾病模型。造模成功后,黄芪甲苷组给予黄芪甲苷40 mg/kg灌胃治疗,正常组、模型组给予等体积生理盐水,每日1次,持续12周。12周后,测定大鼠空腹血糖(FBG)、尿白蛋白/尿肌酐比值(UACR)、血尿素氮(BUN)、血清肌酐(SCr)水平;苏木素-伊红(HE)染色法观察肾脏病理结构变化;过碘酸雪夫(PAS)染色、马松(Masson)染色法观察肾脏纤维化程度;定量聚合酶链反应(qPCR)、蛋白免疫印迹(Western Blot)法检测肾脏组织中腺苷酸蛋白活化激酶(AMPK)、内皮型一氧化氮合酶(e NOS)mRNA及蛋白表达水平。【结果】与模型组比较,黄芪甲苷组大鼠FBG、UACR显著降低(P<0.05),BUN、SCr含量未见明显改变;与模型组比较,黄芪甲苷组大鼠肾小球体积减小,基底膜增厚、系膜基质增生、肾小囊腔狭窄程度、胶原纤维沉积明显减轻;进一步的实验结果显示,黄芪甲苷组肾脏组织中AMPK、e NOS m RNA表达水平较模型组明显升高(P<0.05),AMPK的磷酸化水平及eNOS蛋白表达水平较模型组明显上调(P<0.05)。【结论】黄芪甲苷可改善大鼠糖尿病肾损害,其机制可能与激活AMPK/eNOS信号通路有关。
文摘背景:近年来,有研究发现部分中药单体通过激活细胞自噬可缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,防治皮瓣坏死。目的:综述中药单体调控细胞自噬防治皮瓣坏死的研究进展。方法:分别以“中药、细胞自噬、皮瓣”与“Traditional Chinese Medicine (TCM),Autophagy,Skin flaps”为中英文检索词,由第一作者检索2010年1月至2022年10月发表在中国知网与PubMed数据库的相关文献,文献初筛共检索到相关文献196篇,以纳入和排除标准进行筛选,通过阅读文献标题与摘要进行质量评估,最终归纳整理55篇文献进行综述。结果与结论:(1)细胞自噬的调控是由AMPK/mTOR和PI3K/AKT等信号通路介导的,激活细胞自噬可缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,防治皮瓣坏死。(2)中药单体中的萜类化合物(桦木酸、穿心莲内酯、三七三萜和梓醇)、酚类化合物(白藜芦醇、姜黄素和天麻素)、酚酸类化合物(丹酚酸B)及类固醇类化合物(拟人参皂甙F11)可通过调控相关信号通路激活细胞自噬来缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,促皮瓣存活。(3)文章通过总结中药单体调控细胞自噬防治皮瓣坏死的研究进展,为临床上中药防治皮瓣坏死、促进皮瓣愈合提供参考与理论依据。
