黄芪当归合剂对大鼠急性缺血/再灌注肾损伤的保护及加速修复作用

The protective and accelerating recovery role of Astragali and Angelica on renal ischemia/ reperfusion injury

目的研究黄茂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造成急性缺血／再灌注肾损伤大鼠模型，以黄芪当归合剂灌胃，采用苦味酸法测定血清肌酐，免疫组织化学检测肾组织增殖细胞核抗原（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细胞外信号调节激酶（ＥＲＫ）、氨基末端激酶（ＪＮＫ）活性。结果 与对照组相比，再灌注２４ ｈ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 ｍｉｎ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 ｍｉｎ、２０ ｍｉｎ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。

Objective To investigate the role of Chinese herbs, Astragali and Angelica(A&A) in acute renal ischemia/reperfusion injury, and the related intracellular signal transduction mechanism. Methods Acute ischemic renal injury in rats was made by placing the atraumatic vascular clamp in renal pedical for 45 minutes. Rats in A&A group were given a sigle dose(2 ml/d) of A&A decoction by gastric gavage for 3 days before ischemia, and then continued to the 3th day after ischemia/reperfusion. Serum creatinine(Scr) and renal pathological changes were compared between A&A and control group. The PCNA positive cells in renal tissue were detected by immunohistochemistry. ERK and JNK activity was assayed by specific substrate phosphorylation with immunoprecipitation. Results At 24 hours of reperfusion, Scr value 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 compared to the control. ELK activity decreased at 45 min of ischemia, and recovered at 5 min of reperfusion. There was no difference between two groups. JNK activity did not change after ischemia, but increased at 5 min and peaded at 20 min of reperfusion. It was significantly higher in A&A group than that in the control group. Conclusion Chinese herbs A&A protect kidney against ischemic insult and accelerate the recovery after acute renal ischemia/reperfusion injury, which may associate with the change of JNK signaling pathway.