Tetramethylpyrazine attenuates adriamycin-induced apoptotic injury in rat renal tubular cells NRK-52E
Tetramethylpyrazine attenuates adriamycin-induced apoptotic injury in rat renal tubular cells NRK-52E
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DOI：
10.1055/s-2006-946695
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发表时间：
2006-08-01
期刊：
影响因子：
2.7
通讯作者：
Hsu, Yung-Ho
中科院分区：
文献类型：
--
作者：
Cheng, Chung-Yi;Sue, Yuh-Mou;Hsu, Yung-Ho
川芎嗪（Tetramethylpyrazine，TMP）是从中药大黄中提取的一种有效成分，具有舒张血管、抗血小板等作用，被广泛应用于治疗心血管疾病。研究表明，川芎嗪能清除氧自由基，对大鼠肾脏缺血再灌注损伤具有保护作用。此外，阿霉素诱导的大鼠肾病常用于人类慢性肾脏疾病的药理学研究。已有文献报道阿霉素处理的大鼠出现肾小管细胞凋亡。为了研究TMP对慢性进行性肾脏疾病的治疗潜力，已使用阿霉素诱导的大鼠肾小管细胞NRK-52 E损伤来监测其保护作用。TUNEL染色显示TMP对阿霉素诱导的NRK-52 E细胞凋亡具有剂量依赖性的保护作用。用10或100 μ M的TMP预处理的细胞有效地减少了阿霉素诱导的活性氧（ROS）的形成，如在荧光测定中所测量的。TMP可降低阿霉素诱导的caspase-3、caspase-8和caspase-9活性，抑制阿霉素诱导的细胞色素c释放，提高Bcl-X-L表达。TMP还能够抑制阿霉素处理的NRK-52 E细胞中的死亡受体信号通路，并抑制转录因子NF-κ B的活化。根据本研究的结果，我们认为TMP可以减轻阿霉素诱导的NRK-52 E细胞氧化应激和凋亡损伤，并且可能对肾脏疾病患者具有治疗潜力。
Tetramethylpyrazine (TMP), a compound purified from Rhizoma Ligustici, is a widely used active ingredient in Chinese herbal medicine to treat cardiovascular diseases on account of its vasodilatory actions and antiplatelet activity. Studies have shown that TMP can remove oxygen free radicals and protect rat kidney from ischemia-reperfusion injury. In addition, adriamycin-induced nephrosis in rats is commonly used in pharmacological studies of human chronic renal diseases. Apoptosis of renal tubular cells has been reported in adriamycin-treated rats. To examine the therapeutic potential of TMP on chronic progressive renal diseases, adriamycin-induced injury in rat renal tubular cells NRK-52E has been used to monitor its protective effect. In TUNEL staining, TMP showed a dose-dependent protective effect against adriamycin-induced apoptosis in NRK-52E cells. Pretreatment of the cells with 10 or 100 mu M of TMP effectively decreased the reactive oxygen species (ROS) formation induced by adriamycin, as measured in fluorescent assays. TMP was found to reduce the adriamycin-stimulated activities of caspase-3, caspase-8 and caspase-9, inhibit adriamycin-induced release of cytochrome c, and elevate the expression of Bcl-X-L. TMP was also able to inhibit the death receptor signaling pathway and suppress the activation of transcription factor NF-kappa B in adriamycin-treated NRK-52E cells. Based on the results of this study, we suggest that TMP can attenuate adriamycin-induced oxidative stress and apoptotic injury in NRK-52E cells, and that it may have therapeutic potential for patients with renal diseases.