川芎嗪通过调控fas/fasL的表达对顺铂诱导豚鼠耳蜗毛细胞的抗凋亡机制研究

Study on the anti-apoptotic mechanism of Ligustrazine on the cochlear hair cells of guinea pigs induced by cisplatin by regulating the expression of fas/fasL

目的通过观察川芎嗪对顺铂诱导豚鼠耳蜗组织中fas、fasL及caspase-8蛋白表达水平的影响,探讨其抗凋亡作用的部分机制。方法将60只听力正常的健康白毛红目豚鼠按照随机字数表法随机分为2组:空白组及模型组,空白组豚鼠正常饲养,模型组豚鼠腹腔注射顺铂诱导药物性耳聋模型,模型复制成功后再次将空白组及模型组随机分为2组,即:空白对照组(Blank)、空白+川芎嗪组(Blank+Ligustrazine)、模型对照组(Model)、模型+川芎嗪组(Model+Ligustrazine)。空白+川芎嗪组及模型+川芎嗪组豚鼠腹腔注射川芎嗪注射液进行干预,2周后处死豚鼠,对各组豚鼠耳蜗组织中fas、fasL及caspase-8蛋白表达水平进行检测。结果模型评价:与空白组相比,模型组豚鼠ABR阈值显著提高(P<0.01);空白组豚鼠耳蜗毛细胞排列整齐、均匀,无缺失及坏死细胞出现;模型组豚鼠耳蜗毛细胞变形明显,排列不均,溶解破坏的毛细胞较多,提示造模成功。各组豚鼠耳蜗组织中fas、fasL、caspase-8蛋白表达水平结果显示,与空白对照组和空白+川芎嗪组比较,模型对照组豚鼠耳蜗组织中fas、fasL、caspase-8蛋白表达水平均显著升高(P<0.01),与模型对照组比较,模型+川芎嗪组豚鼠耳蜗组织中fas、fasL、caspase-8蛋白表达水平显著降低(P<0.01)。结论川芎嗪可通过调控fas、fasL、caspase-8的表达水平来抑制细胞凋亡的发生,发挥其抗凋亡作用。

Objective By observing the index of fas、fasL and caspase-8 protein of guinea pigs＇ cochlear tissue induced by cisplatin, to explore the part of the mechanisms of anti-apoptotic effect. Method The 60 healthy and normal hearing guinea pigs were randomly divided into 2 groups according to the random number table method： the blank group and the model group. The guinea pigs of the blank group were normally reared, while the guinea pigs of the model group were injected with intraperitoneally cisplatin to make deafness model. After the model replication was successful, the blank group and model group were divided into 2 groups once again,namely： blank control group（Blank）, blank ＋ Ligustrazine group（Blank＋Ligustrazine）, model control group（Model）, model ＋Ligustrazine group（Model＋Ligustrazine）. The guinea pigs of the Blank＋Ligustrazine group and the Model＋Ligustrazine group were intraperitoneally injected with ligustrazine injection. The guinea pigs were killed after 2 weeks to detect the expression of fas、fasL and caspase-8 proteins in the cochlea tissues of guinea pigs in each group. Result Model evaluation： compared with the blank group, the ABR threshold of the guinea pigs in the model group was significantly improved（P〈0.01）; The guinea pig cochlear hair cells of the blank group were arranged in neat and uniform, and there were no deletions and necrotic cells. The guinea pig cochlear hair cells of the model group were deformed obviously, arranged unevenly, dissolved and damaged more, suggesting that the model was successful. The expression levels of fas、fasL and caspase-8 in cochlear tissues of guinea pigs in the model control group were significantly higher than those the blank control group and the blank ＋ Ligustrazine group（P〈0.01）. Compared with the model control group, the expression levels of fas、fasL and caspase-8 in cochlear tissues of guinea pigs in the model ＋ Ligustrazine group decreased significantly（P〈0.01）.Conclusion Ligustrazine can inhibit the occurrence of apoptosis by regulating the expression levels of fas, fasL, caspase-8, and exert its anti-apoptotic effect.