Acidosis in local environment plays a critical role in cell injury. One key mediator of acidosis-induced cell injury is the acid-sensing ion channels (ASICs), particularly ASIC1a. Herein, we investigated the role of A...Acidosis in local environment plays a critical role in cell injury. One key mediator of acidosis-induced cell injury is the acid-sensing ion channels (ASICs), particularly ASIC1a. Herein, we investigated the role of ASIC1a in acid-induced vascular endothelial cell injury of Henoch-Schonlein purpura (HSP) children. Acid-induced ASIC1a, Calpain and Calcineurin expression in vascular endothelial cells pretreated with IgA1 isolated from HSP were detected by real time quantitative polymerase chain reaction and western blot methods, respectively. Cell cytotoxicity was measured by interleukin-8 and nitric oxide production with ELISA. The results showed acid-induced ASIC1a, Calpain and Calcineurin expression in cells increased, especially at PH6.5. The cytotoxicity of vascular endothelial cells was increased by extracellular acidosis. Moreover non-specific or specific blockers of ASIC1a, Amiloride and PcTX-1 could remarkably decrease these parameters. These findings show that increased [Ca<sup>2+</sup>]i, mediated via ASIC1a, might contribute to acid-induced vascular endothelial cell injury of HSP.展开更多
Background: Henoch-Schonlein purpura (HSP) is a kind of systemic small vessel vasculitis in children. Endothelium cells injury induced by IgA1 is considered important in the pathogenesis of HSP. Research found that th...Background: Henoch-Schonlein purpura (HSP) is a kind of systemic small vessel vasculitis in children. Endothelium cells injury induced by IgA1 is considered important in the pathogenesis of HSP. Research found that the apoptosis of vein endothelial cells was related to the vasculitis in HSP patients. Purpose: To observe the effect of IgA1 from HSP patients on the apoptosis of HUVEC and firstly analyze the mechanism of the apoptosis of HUVEC induced by IgA1. Methods: HUVECs were cultured in 3 different conditional media with IgA1 from HSP patients, normal healthy children and simply medium (blank control). Serum IgA1 was purified by jacalin affinity chromatography. The rates of apoptosis in HUVEC incubated with IgA1 were determined by TUNEL method and flow cytometry, respectively. The expression of the cytoskeletal proteins, such as FAK, Vinculin and MLCK was detected with the methods of Real-time PCR and Westernblot, respectively. Results: The present study showed that the apoptosis rate of HUVEC by IgA1 isolated from HSP patients was higher than blank control (14.77% ± 2.23% vs 2.25% ± 0.77%) (P < 0.01) and the rate of HUVEC by IgA1 from normal healthy children was higher than blank control (9.97% ± 1.48% vs 2.25% ± 0.77%) (P < 0.01). The cytoskeletal proteins, such as FAK, Vinculin and MLCK expression were down-regulated in HUVEC co-cultured with IgA1 isolated from HSP patients for 24h. Conclusion: These findings firstly on IgA1 from HSP patients may induce apoptosis of vascular endothelial cells through inhibiting the cytoskeletal proteins expression. IgA1 may accelerate progression of HSP by inducing apoptosis of vascular endothelial cells.展开更多
目的评价血液灌流治疗儿童过敏性紫癜的疗效。方法检索PubMed、Ovid、web of Science、Embase、Cochrane Library、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)、中文科技期刊数据库(VIP)和万方数据库,并辅以手工检索,检索...目的评价血液灌流治疗儿童过敏性紫癜的疗效。方法检索PubMed、Ovid、web of Science、Embase、Cochrane Library、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)、中文科技期刊数据库(VIP)和万方数据库,并辅以手工检索,检索时间均从建库至2015年6月30日公开发表的血液灌流治疗儿童过敏性紫癜的随机对照试验或临床对照实验,筛选符合标准的研究,应用Jadad评分法进行质量评价,使用Rev Man 5.0软件进行Meta分析。结果共7篇文献纳入研究,其中随机对照试验(RCT)6篇,临床对照试验(CCT)1篇,研究对象共416例,其中血液灌流组216例,对照组200例。Meta分析结果显示,血液灌流组与对照组缩短皮疹持续时间,其合并加权均数差(WMD)=-1.13(95%CI:-1.38^-0.87,P<0.00001);缩短腹痛持续时间,其合并WMD=-1.23(95%CI:-1.46^-0.99,P<0.00001);缩短关节肿痛持续时间,其合并WMD=-0.91(95%IC:-1.13^-0.70,P<0.00001)。结论血液灌流联合药物等支持治疗能有效缓解儿童过敏性紫癜的临床症状,但其疗效需要大样本、多中心、设计良好的RCT进一步验证。展开更多
文摘Acidosis in local environment plays a critical role in cell injury. One key mediator of acidosis-induced cell injury is the acid-sensing ion channels (ASICs), particularly ASIC1a. Herein, we investigated the role of ASIC1a in acid-induced vascular endothelial cell injury of Henoch-Schonlein purpura (HSP) children. Acid-induced ASIC1a, Calpain and Calcineurin expression in vascular endothelial cells pretreated with IgA1 isolated from HSP were detected by real time quantitative polymerase chain reaction and western blot methods, respectively. Cell cytotoxicity was measured by interleukin-8 and nitric oxide production with ELISA. The results showed acid-induced ASIC1a, Calpain and Calcineurin expression in cells increased, especially at PH6.5. The cytotoxicity of vascular endothelial cells was increased by extracellular acidosis. Moreover non-specific or specific blockers of ASIC1a, Amiloride and PcTX-1 could remarkably decrease these parameters. These findings show that increased [Ca<sup>2+</sup>]i, mediated via ASIC1a, might contribute to acid-induced vascular endothelial cell injury of HSP.
基金supported by the Project supported by the National Natural Science Foundation of China(NO 81001339).
文摘Background: Henoch-Schonlein purpura (HSP) is a kind of systemic small vessel vasculitis in children. Endothelium cells injury induced by IgA1 is considered important in the pathogenesis of HSP. Research found that the apoptosis of vein endothelial cells was related to the vasculitis in HSP patients. Purpose: To observe the effect of IgA1 from HSP patients on the apoptosis of HUVEC and firstly analyze the mechanism of the apoptosis of HUVEC induced by IgA1. Methods: HUVECs were cultured in 3 different conditional media with IgA1 from HSP patients, normal healthy children and simply medium (blank control). Serum IgA1 was purified by jacalin affinity chromatography. The rates of apoptosis in HUVEC incubated with IgA1 were determined by TUNEL method and flow cytometry, respectively. The expression of the cytoskeletal proteins, such as FAK, Vinculin and MLCK was detected with the methods of Real-time PCR and Westernblot, respectively. Results: The present study showed that the apoptosis rate of HUVEC by IgA1 isolated from HSP patients was higher than blank control (14.77% ± 2.23% vs 2.25% ± 0.77%) (P < 0.01) and the rate of HUVEC by IgA1 from normal healthy children was higher than blank control (9.97% ± 1.48% vs 2.25% ± 0.77%) (P < 0.01). The cytoskeletal proteins, such as FAK, Vinculin and MLCK expression were down-regulated in HUVEC co-cultured with IgA1 isolated from HSP patients for 24h. Conclusion: These findings firstly on IgA1 from HSP patients may induce apoptosis of vascular endothelial cells through inhibiting the cytoskeletal proteins expression. IgA1 may accelerate progression of HSP by inducing apoptosis of vascular endothelial cells.
文摘目的评价血液灌流治疗儿童过敏性紫癜的疗效。方法检索PubMed、Ovid、web of Science、Embase、Cochrane Library、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)、中文科技期刊数据库(VIP)和万方数据库,并辅以手工检索,检索时间均从建库至2015年6月30日公开发表的血液灌流治疗儿童过敏性紫癜的随机对照试验或临床对照实验,筛选符合标准的研究,应用Jadad评分法进行质量评价,使用Rev Man 5.0软件进行Meta分析。结果共7篇文献纳入研究,其中随机对照试验(RCT)6篇,临床对照试验(CCT)1篇,研究对象共416例,其中血液灌流组216例,对照组200例。Meta分析结果显示,血液灌流组与对照组缩短皮疹持续时间,其合并加权均数差(WMD)=-1.13(95%CI:-1.38^-0.87,P<0.00001);缩短腹痛持续时间,其合并WMD=-1.23(95%CI:-1.46^-0.99,P<0.00001);缩短关节肿痛持续时间,其合并WMD=-0.91(95%IC:-1.13^-0.70,P<0.00001)。结论血液灌流联合药物等支持治疗能有效缓解儿童过敏性紫癜的临床症状,但其疗效需要大样本、多中心、设计良好的RCT进一步验证。