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机构地区:[1]北京医科大学第一医院肾内科北京医科大学肾脏病研究所,北京100034
出 处:《Chinese Medical Journal》2001年第2期7-11,102-103,共7页中华医学杂志(英文版)
基 金:DoctorateGrant! (95 0 10 2 9);OutstandingPersonalGrant! (3 9910 2 10 474 2 3 1 C0 4)fromChineseEducationMinistry
摘 要:Objective To investigate the role of Astragali and Angelica (A&A) of Chinese herbs in acute renal ischemia/reperfusion injury, and the related intracellular signal transduction mechanism. Methods Acute ischemic renal injury in rats was induced by clamping in renal pedicel for 45 minutes. Rats in therapy group were given a single dose (2 ml/day) of A&A for 3 days before clamping, and then continued for another 3 days. Forty-five minutes after clamping and at different reperfusion time, serum creatinine (Scr) and renal pathological changes were taken and compared in both groups. The proliferating cell nuclear antigen (PCNA) positive cells were detected by immunohistochemistry. Extracelluar regulating kinase (ERK) and c-Jun N-terminal kinase (JNK) activity was assayed by specific substrate phosphorylation with immunoprecipitation. Results At the 24th hour of reperfusion, Scr was lower in A&A group than that in the control. Much less necrotic tubular cells, casts, and more PCNA-positive cells were found in A&A group. ERK activity decreased after clamping, and recovered at 5 minutes of reperfusion. There was no difference between the two groups. JNK activity did not change after ischemia, but increased at 5 minutes and peaked at 20 minutes of reperfusion. JNK activity was significantly higher in A&A group than that in the control group. Conclusion A&A protected kidney against ischemic insult and accelerated both functional and histological recovery after acute renal ischemia/reperfusion injury, which may associate with the change of JNK signaling pathway.目的 研究中药黄芪当归合剂在急性缺血 /再灌注肾损伤修复过程中的作用及其细胞内信号转导机制。方法 无创动脉夹夹闭双侧肾蒂 4 5分钟造成急性缺血 /再灌注肾损伤大鼠模型 ,夹闭前以黄芪当归合剂 (2ml/d)灌胃共三天 ,于缺血 4 5分钟及再灌注不同时间后分别测定血清肌酐、观察病理变化 ,以免疫组化法检测肾组织PCNA的表达及分布、特异性底物磷酸化结合免疫沉淀法测定肾组织ERK、JNK活性结果 与对照组相比 ,再灌注 2 4小时给药组大鼠血肌酐升高幅度降低 ,肾小管上皮细胞坏死减少 ,PCNA阳性细胞明显增多。单纯缺血使肾组织ERK活性降低 ,再灌注 5分钟其活性恢复 ,给药组与对照组无差异 ;单纯缺血对JNK活性无明显影响 ,再灌注 5分钟、2 0分钟时给药组JNK活性明显增高。结论 黄芪当归合剂可减轻急性缺血 /再灌注肾损伤、促进损伤修复 ,这一作用可能与其影响缺血再灌注后JNK信号通路的变化有关。
关 键 词:astragali and angelica ischemia and reperfusion signal transduction
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