马传荣 汪燕 贺国芳 方建国 杜光 姜汉英 (华中科技大学同济医学院附属同济医院药学部 武汉 430030)
摘 要 目的：通过研究不同浓度的川芎嗪（tertramethylpyrazine, TMP）在大鼠肾脏缺血再灌注损伤过程中的作用，探讨川芎嗪对肾脏组织发挥保护作用的最佳浓度。方法：建立大鼠肾脏缺血再灌注模型，分别检测假手术组、模型组、川芎嗪用药组（川芎嗪15，30，45，60，90 mg•kg-1）血肌酐（Cr）和尿素氮（BUN）水平，观察肾组织形态并测定其中的诱导型一氧化氮合酶(induced nitric oxide synthase, iNOS)活性。结果：15mg•kg-1和30 mg•kg-1组川芎嗪显著降低肾组织内iNOS的活性，降低血浆Cr和BUN水平，减轻肾小管上皮细胞坏死程度，以15 mg•kg-1最为显著；45 mg•kg-1组血Cr和BUN水平及肾小管坏死程度低于模型组，但高于假手术组，且均有显著性差异；60 mg•kg-1组和90 mg•kg-1组血Cr和BUN反而上升，小管上皮细胞坏死比模型组明显加重，肾组织内iNOS较模型组变化不明显。结论：合适剂量（15～45 mg•kg-1）的川芎嗪可以通过降低iNOS活性，保护缺血再灌注肾功能，减轻肾组织病理损害，以15 mg•kg-1最为显著，随剂量增加保护作用减弱。而较高浓度（45～90 mg•kg-1）川芎嗪失去对缺血再灌注肾脏的保护作用。
关键词 川芎嗪；缺血再灌注损伤；诱导型一氧化氮合酶
中图分类号：R285.5
文献标识码：A
文章编号：1008-049X(2007)11-1051-03
Effects of Tertramethylpyrazine(TMP) in Kidney Ischemia Reperfusion in Rats
Ma Chuanrong，Wang Yan，He Guofang, Fang Jianguo, Du Guang, Jiang Hanying( Department of Pharmacology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Wuhan 430030， China)
ABSTRACT Objective:To explore the effects and the optimal protective dose of tertramethylpyrazine (TMP) in kidney ischemia reperfusion in rats based on different concentration.Method:The rats were randomly divided into three groups: sham operation group, ischemia-reperfusion group and treatment group(TMP 15，30，45，60，90 mg•kg-1 by intravenous injection respectively).The renal ischemia reperfusion models were established. Serum levels of blood creatinine (Cr) and urea nitrogen (BUN) were measured. The activities of iNOS in kidney and the pathological variety were detected in all rats.Result:Compared to ischemia-reperfusion group,TMP 15 mg•kg-1 and 30 mg•kg-1presented with significantly lower levels of Cr and BUN (P<0.01，P<0.01)than those in the model group. Moreover the activity of iNOS in kidney was decreased markedly (P<0.01，P<0.01).The renal tubular epithelial cell showed less edema, denaturation or necrosis and apoptosis were alleviated markedly, especially the TMP 15 mg•kg-1 group. The renal function and the tubular epithelial cell death damage in TMP 45 mg•kg-1group were decreased, but were aggravated than sham operation group. TMP 60 mg•kg-1 and 90 mg•kg-1increased the levels of Cr and BUN in plasma and the histological lesions and apoptosis of renal tissue was significantly aggravated compared with sham operation group, however the change of activities of iNOS in kidney were not obvious.Conclusion: TMP of appropriate dose（15-45 mg•kg-1） were proved to have protective effect on renal function and relieve the pathological lesion of renal tissue through decreasing the activity of iNOS in kidney after ischemia-reperfusion injury,especially the TMP 15 mg•kg-1; Following the dose of TMP increased,the protective effect is lessened .However high concentration of TMP（45-90 mg•kg-1） lost its protective effect on ischemia reperfusion kidney.
KEY WORDS Tertramethylpyrazine;Renal ischemia reperfusion injury; Induced nitric oxide synthase
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