川芎嗪拮抗顺铂所致豚鼠耳毒性的作用

目的观察川芎嗪对顺铂所致豚鼠耳毒性的拮抗作用并探讨其机制。方法将30只健康豚鼠随机分为3组,每组10只。正常对照组：每天腹腔注射生理盐水3 mL/kg,连续7天;顺铂组：每天腹腔注射顺铂3 mg/kg,连续7天;中药拮抗组：每天腹腔注射川芎嗪140 mg/kg,共3天,第4天起每天腹腔注射川芎嗪140 mg/kg,30 min后,对侧腹腔注射顺铂3 mg/kg,连续7天。每组动物给药前后均行听觉脑干诱发电位（BAEP）检测;末次检测完毕后,在麻醉状态下将豚鼠断头取耳蜗,每组半数标本进行硝酸银染色耳蜗基底膜铺片;半数标本制备石蜡切片,部分用于DNA末端转移酶介导的缺口末端标记法（TUNEL）检测耳蜗内细胞凋亡,部分采用免疫组织化学法检测耳蜗内氨基末端激酶（JNK）信号途径蛋白质c-Jun的表达。结果用药前3组动物BAEP阈值差异无统计学意义（P〉0.05）,用药后顺铂组与中药拮抗组BAEP阈值均明显升高（P〈0.05）,且顺铂组高于中药拮抗组（P〈0.05）。顺铂组毛细胞大片缺失,螺旋神经节细胞数明显减少,TUNEL阳性细胞数较多,免疫组化c-Jun表达较强,而中药拮抗组上述损害均较顺铂组明显减轻（P〈0.05）。结论川芎嗪对顺铂所致豚鼠耳蜗损伤有一定拮抗作用,机制可能与其清除耳蜗组织内氧自由基、改善微循环、抗凋亡有关。

Ligustrazine Fought against Cisplatin Induced Ototoxicity in Guinea Pigs

Objective To study the protective effect of Ligustrazine Injection （LI） against cispla- tin-induced ototoxicity and to explore its mechanism. Methods Thirty healthy adult guinea pigs were ran- domly divided into three groups, 10 in each group, i.e., the normal control group, the cisplatin group, and the LI group. Guinea pigs in the normal control group were intraperitoneally injected with normal saline at 3 mL/kg for 7 consecutive days. Those in the cisplatin group were intraperitoneally injected with cisplatin at 3 mg/kg for 7 consecutive days. Those in the LI group were intraperitoneally injected with LI at 140 mg/kg for 7 days, but cisplatin （3 mg/kg） was intraperitoneally injected from the opposite side starting from the 4th day. Brainstem auditory evoked potential （BAEP） was performed in all animals before and after injec- tion. All animals were sacrificed after the final testing under anesthesia and their cochleas collected. Half the cochleas of each group were collected for silver nitrate staining of cochlear basilar membrane stretched. The other half the cochleas of each group made into paraffin sections to observe the apoptosis of cochlea cells by TUNEL method and the expression levels of c-Jun detected by immunohistochemistry. Results There was no statistical difference in the difference of BAEP threshold among the 3 groups be- fore injection （P 〉0.05）, but the BAEP threshold increased in the cisplatin group and the LI group （P 〈 0.05）. Besides, it was higher in the cisplatin group （P 〈0.05）. In the cisplatin group, most hair cells were missing, spiral ganglion cells obviously decreased, more TUNEL positive cells occurred, and the expression of c-Jun was stronger. But the aforesaid impairment in the LI group was obviously lessened（P 〈0.05）. Conclusions LI showed certain antagonist effect on cisplatin-induced ototoxicity. Its mecha- nism might be associated with scavenging oxygen radicals of the cochlea tissue, improving the microcir- culation, and fighting against apo