肉芽肿性多血管炎(granulomatosis with polyangiitis,GPA)是一种原发性、坏死性、肉芽肿性小血管炎,大多数患者出现血清学抗蛋白酶3(RR3)及抗中性粒细胞胞质抗体(ANCA)阳性[1],其临床表现多样,通常可影响耳、鼻、眼、呼吸道、肾脏等器...肉芽肿性多血管炎(granulomatosis with polyangiitis,GPA)是一种原发性、坏死性、肉芽肿性小血管炎,大多数患者出现血清学抗蛋白酶3(RR3)及抗中性粒细胞胞质抗体(ANCA)阳性[1],其临床表现多样,通常可影响耳、鼻、眼、呼吸道、肾脏等器官,并可累及神经系统、皮肤等。GPA的治疗包括诱导缓解和维持治疗,其中诱导缓解时主要以糖皮质激素联合环磷酰胺(CTX)或利妥昔单抗(RTX)为主。虽然大多数GPA患者经过正规有效的治疗可得到有效缓解,但机会感染的风险明显增加[2],尤其是肺孢子菌肺炎(pneumocystis pneumonia,PCP)最为凶险致命,且常出现在诱导缓解及初始治疗的前12个月[3]。因此,及早对GPA患者开展有效的PCP预防极为重要。展开更多
In our previous study, we have elucidated the chemical profile ofYGS40, a fraction of Yi-Gan San （YGS）, used for the treatment of Alzheimer＇s disease （AD）. Oxidative stress-induced apoptosis is implicated in neur...In our previous study, we have elucidated the chemical profile ofYGS40, a fraction of Yi-Gan San （YGS）, used for the treatment of Alzheimer＇s disease （AD）. Oxidative stress-induced apoptosis is implicated in neurodegenerative disorders such as AD. The aim of the present study was to explore the protective effects of YGS40 against hydrogen peroxide （H202）-induced apoptosis in PC12 cells and the underlying mechanisms. PC12 cells were exposed to 100 μmol·L 1 of H202 for 12 h with or without YGS40 pretreatment. Cytotoxicity was determined by MTT （3, （4, 5-dimethylthiazole-2-yl） 2, 5-diphenyl-tetrazolium bromide） and lactate dehydrogenase （LDH） release assays; apoptosis was detected by Annexin V/propidium iodide coupled staining and by determining caspase-3 activity and Bax and Bcl-2 protein levels. Mitochondrial membrane potential （MMP） was assessed by the retention of rhodamine123; and the activities of superoxide dismutase （SOD） and malondialdehyde （MDA） were measured using commercially available enzymatic kits. Pretreatment with YGS40 significantly prevented H2O2-induced cytotoxicity and protected the cells against H2O2-triggered apoptosis characterized by extemalization of membrane phosphatidylserine and caspase-3 activation and the increased ratio of Bax/Bcl-2 in PC12 cells. Further studies showed that YGS40 suppressed H2O2-induced MMP loss, increased SOD activity, and decreased MDA level. These findings suggest that YGS40 may be beneficial for the prevention and treatment of oxidative stress-mediated disorders.展开更多
文摘肉芽肿性多血管炎(granulomatosis with polyangiitis,GPA)是一种原发性、坏死性、肉芽肿性小血管炎,大多数患者出现血清学抗蛋白酶3(RR3)及抗中性粒细胞胞质抗体(ANCA)阳性[1],其临床表现多样,通常可影响耳、鼻、眼、呼吸道、肾脏等器官,并可累及神经系统、皮肤等。GPA的治疗包括诱导缓解和维持治疗,其中诱导缓解时主要以糖皮质激素联合环磷酰胺(CTX)或利妥昔单抗(RTX)为主。虽然大多数GPA患者经过正规有效的治疗可得到有效缓解,但机会感染的风险明显增加[2],尤其是肺孢子菌肺炎(pneumocystis pneumonia,PCP)最为凶险致命,且常出现在诱导缓解及初始治疗的前12个月[3]。因此,及早对GPA患者开展有效的PCP预防极为重要。
基金supported by the National Natural Science Foundation of China(Nos.81274046 and 81373956)
文摘In our previous study, we have elucidated the chemical profile ofYGS40, a fraction of Yi-Gan San （YGS）, used for the treatment of Alzheimer＇s disease （AD）. Oxidative stress-induced apoptosis is implicated in neurodegenerative disorders such as AD. The aim of the present study was to explore the protective effects of YGS40 against hydrogen peroxide （H202）-induced apoptosis in PC12 cells and the underlying mechanisms. PC12 cells were exposed to 100 μmol·L 1 of H202 for 12 h with or without YGS40 pretreatment. Cytotoxicity was determined by MTT （3, （4, 5-dimethylthiazole-2-yl） 2, 5-diphenyl-tetrazolium bromide） and lactate dehydrogenase （LDH） release assays; apoptosis was detected by Annexin V/propidium iodide coupled staining and by determining caspase-3 activity and Bax and Bcl-2 protein levels. Mitochondrial membrane potential （MMP） was assessed by the retention of rhodamine123; and the activities of superoxide dismutase （SOD） and malondialdehyde （MDA） were measured using commercially available enzymatic kits. Pretreatment with YGS40 significantly prevented H2O2-induced cytotoxicity and protected the cells against H2O2-triggered apoptosis characterized by extemalization of membrane phosphatidylserine and caspase-3 activation and the increased ratio of Bax/Bcl-2 in PC12 cells. Further studies showed that YGS40 suppressed H2O2-induced MMP loss, increased SOD activity, and decreased MDA level. These findings suggest that YGS40 may be beneficial for the prevention and treatment of oxidative stress-mediated disorders.
