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目的:观察顺铂诱导豚鼠耳聋后,耳蜗组织中p53、caspase3表达水平的变化,同时探讨川芎嗪对耳聋豚鼠模型的部分干预机制。方法:40只豚鼠随机分为空白组(B)和模型组(M),每组20只,对M组豚鼠进行耳聋模型复制,模型复制成功后,将B组及M组进行第二次随机分组,各自再次随机分为两组,分别为:空白对照组(B1)、空白+川芎嗪组(B2)、模型对照组(M1)、模型+川芎嗪组(M2),B2及M2组豚鼠均经腹腔注射川芎嗪注射液,剂量为140 mg/kg,每日1次,连续2周。B1及M1组豚鼠经腹腔注射等量生理盐水,每日1次,连续2周。末次给药后1 h,处死豚鼠,采用荧光定量PCR法对各组豚鼠耳蜗组织中p53、caspase3 mRNA表达水平进行检测;采用Western-blot法对各组豚鼠耳蜗组织中p53、caspase3蛋白表达水平进行检测。结果:各组豚鼠耳蜗组织中p53、caspase3 mRNA及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p53、caspase3 mRNA及蛋白表达水平显著升高(P<0.001);与模型对照组比较,模型+川芎嗪组豚鼠耳蜗组织中p53、caspase3 mRNA及蛋白表达水平显著降低(P<0.01)。结论:顺铂诱导豚鼠耳聋后,耳蜗组织中p53、caspase3 mRNA及蛋白表达水平升高,川芎嗪可下调顺铂诱导的耳聋模型豚鼠耳蜗组织中p53、caspase3 mRNA及蛋白表达水平。
Objective: To observe the changes of p53, caspase3 expression in cochlear after cisplatin-induced deafness in guinea pigs, and to explore the mechanism of ligustrazine in guinea pigs with deafness. Methods: Forty guinea pigs were randomly divided into blank group (B) and model group (M), with 20 mice in each group. The deafness model was replicated in M guinea pigs. After the model was successfully replicated, The rats were randomly divided into two groups: blank control group (B1), blank + ligustrazine group (B2), model control group (M1), model group + ligustrazine group (M2) All rats were injected intraperitoneally with Ligustrazine injection at the dose of 140 mg / kg once daily for 2 weeks. The B1 and M1 guinea pigs were injected intraperitoneally with normal saline once a day for 2 weeks. At 1 h after the last administration, guinea pigs were sacrificed and the expression of p53 and caspase3 mRNA in cochleas of each group were detected by real-time PCR. The expressions of p53 and caspase 3 in cochlear of each group were detected by Western-blot Detection. Results: The mRNA and protein expression levels of p53 and caspase3 in cochlear of guinea pigs in each group showed that the expression of p53 and caspase3 mRNA and protein in cochlear of model control group were significantly increased compared with the blank control group and the blank + ligustrazine group P <0.001). Compared with the model control group, the mRNA and protein expressions of p53 and caspase3 in guinea pig cochleas in model group and ligustrazine group were significantly decreased (P <0.01). CONCLUSION: Cisplatin induces the expression of p53 and caspase3 mRNA and protein in guinea pig cochlea after cisplatin-induced deafness. P53 and caspase3 mRNA and protein expression in cochlear of cisplatin-induced deafness model can be down-regulated by ligustrazine.