川芎嗪对顺铂耳聋大鼠耳蜗Fas/Fas L及caspase8的调控研究

摘要

观察川芎嗪对顺铂诱导的耳聋模型大鼠耳蜗毛细胞的抗凋亡作用，并探索其抗凋亡的部分作用机制。方法120只SPF级Wistar分为4组，正常对照组；正常+川芎嗪组；模型对照组；模型加川芎嗪组。采用顺铂腹腔注射的方法诱导药物性耳聋大鼠模型，通过川芎嗪腹腔注射对顺铂耳聋模型大鼠进行干预，采用听觉脑干诱发电位ABR阈值的检测及大鼠耳蜗基底膜铺片的方法对模型进行评价，并对各组大鼠耳蜗组织中Fas、Fas L和caspase-8 mRNA及蛋白表达水平进行检测。结果模型对照组大鼠ABR阈值明显高于正常对照组，川芎嗪具有一定的降低顺铂耳聋模型大鼠ABR阈值的作用；顺铂耳聋模型大鼠耳蜗毛细胞明显溶解缺失、排列紊乱等病理改变；模型对照组大鼠耳蜗组织中Fas、Fas L和caspase-8 mRNA及蛋白表达水均显著高于正常对照组，经川芎嗪腹腔注射干预后，三者表达水平得到了一定的控制。结论顺铂可诱导药物性耳聋大鼠模型，川芎嗪对耳聋模型大鼠具有一定的干预作用；顺铂腹腔注射可导致大鼠耳蜗组织中Fas、Fas L和caspase-8 mRNA及蛋白表达水平，而川芎嗪注射液可能是通过抑制Fas、Fas L和caspase-8 mRNA及蛋白的表达水平而实现其抗凋亡作用。%Objective The anti apoptosis effect of Ligustrazine against cisplatin induced hearing loss model rat cochlear hair cells, and to explore its anti apoptotic mechanisms. Method 120 SPF Wistar were divided into 4 groups, normal control group;normal+tetramethylpyrazine group;model group;model of Kagawa group. The model drug deafness rats induced by in⁃traperitoneal injection of cisplatin by intraperitoneal injection, ligustrazine intervention on cisplatin deafness model rat cochle⁃ar basilar membrane, method detection of brainstem auditory evoked potentials of ABR threshold and rat stretched the model was evaluated, and to detect the level of Fas, Fas L and caspase8 mRNA and protein expression in cochlear tissues of rats in each group. Results The model control threshold of ABR rats was significantly higher than that in normal control group, ligust⁃razine can decrease ABR threshold cisplatin deafness model rats;change of cisplatin in rat cochlea hair cells loss model was dissolved, disorganized, lack of Pathology;water were significantly higher than those in normal control group Fas, Fas L and cas⁃pase-8 mRNA and protein expression of the control group rat cochlear model by intraperitoneal injection, ligustrazine interven⁃tion, three expression level to be a certain control. Conclusions Cisplatin induced rat model of drug-induced deafness, ligust⁃razine has certain intervention effect on deaf rat model;intraperitoneal injection of cisplatin can result in cochlear tissues in rats Fas, Fas L and caspase8 mRNA and protein expression level, and ligustrazine injection may be to achieve its anti apoptotic effects through inhibition of Fas, Fas expression level L and caspase8 mRNA and protein.