Wang Xiao-Yan, Ma Zeng-Chun, Wang Yu-Guang, Tan Hong-Ling, Xiao Cheng-Rong, Liang Qian-De, Tang Xiang-Lin, Cheng Yu, Gao Yue
Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China; Chongqing Maternal and Child Health-Care Hospital, Chongqing 400016, China.
Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China.
Chin J Nat Med. 2014 Oct;12(10):730-7. doi: 10.1016/S1875-5364(14)60112-6. Epub 2014 Oct 31.
Radiation induces an important apoptosis response in irradiated organs. The objective of this study was to investigate the radioprotective effect of tetramethylpyrazine (TMP) on irradiated lymphocytes and discover the possible mechanism of protection.
Lymphocytes were pretreated for 12 h with TMP (25-200 μmol·L(-1)) and then exposed to 4 Gy radiation. Cell apoptosis and the signaling pathway were analyzed.
Irradiation increased cell death, DNA fragmentation, activated caspase activation and cytochrome c translocation, downregulated B-cell lymphoma 2 (Bcl-2) and up-regulated Bcl-2-associated X protein (Bax). Pretreated with TMP significantly reversed this tendency. Several anti-apoptotic characteristics of TMP, including the ability to increase cell viability, inhibit caspase-9 activation, and upregulate Bcl-2 and down-regulate Bax in 4Gy-irradiated lymphocytes were determined. Signal pathway analysis showed TMP could translate nuclear factor-κB (NF-κB) from cytosol into the nucleus.
The results suggest that TMP had a radioprotective effect through the NF-κB pathway to inhibit apoptosis, and it may be an effective candidate for treating radiation diseases associated with cell apoptosis.
辐射可诱导受照射器官产生重要的凋亡反应。本研究的目的是探讨川芎嗪（TMP）对受照射淋巴细胞的辐射防护作用，并发现可能的保护机制。
淋巴细胞用TMP（25 - 200μmol·L⁻¹）预处理12小时，然后接受4 Gy辐射。分析细胞凋亡及信号通路。
辐射增加细胞死亡、DNA片段化，激活半胱天冬酶激活及细胞色素c易位，下调B细胞淋巴瘤2（Bcl - 2）并上调Bcl - 2相关X蛋白（Bax）。用TMP预处理可显著逆转这种趋势。确定了TMP的几种抗凋亡特性，包括增加细胞活力、抑制半胱天冬酶 - 9激活以及上调4 Gy照射淋巴细胞中的Bcl - 2并下调Bax。信号通路分析表明TMP可将核因子 - κB（NF - κB）从细胞质转运到细胞核。
结果表明TMP通过NF - κB途径具有辐射防护作用以抑制凋亡，它可能是治疗与细胞凋亡相关的辐射疾病的有效候选药物。
