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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。
Objective To observe the antagonistic effect of ligustrazine on ototoxicity induced by cisplatin in guinea pigs and to explore its mechanism. Methods Thirty healthy guinea pigs were randomly divided into 3 groups with 10 in each group. Normal control group: intraperitoneal injection of normal saline 3 mL / kg daily for 7 days; cisplatin group: intraperitoneal injection of cisplatin 3 mg / kg daily for 7 days; antagonist group: intraperitoneal injection of tetramethylpyrazine 140 mg / kg, A total of three days, the first four days after intraperitoneal injection of tetramethylpyrazine 140 mg / kg, 30 min, contralateral abdominal cisplatin 3 mg / kg for 7 days. The auditory brainstem response (BAEP) was measured before and after administration in each group. After the last test, the cochleas were removed from the guinea pigs under anesthesia, and half of them were stained with silver nitrate stained basement membrane. Half of the specimens Paraffin sections were prepared and partially used for detection of apoptosis in the cochlea by DNA-terminal-transferase-mediated nick end labeling (TUNEL). The cochlear N-terminal kinase (JNK) signaling pathway proteins were partially detected by immunohistochemistry for c-Jun expression. Results There was no significant difference in BAEP threshold between the three groups before treatment (P> 0.05). After treatment, the BAEP threshold of cisplatin group and traditional Chinese medicine group were significantly increased (P <0.05) P <0.05). Cisplatin group hair loss, spiral ganglion cells significantly reduced the number of TUNEL-positive cells, immunohistochemical c-Jun expression was stronger, while the traditional Chinese medicine antagonist group were significantly lower than the cisplatin damage (P <0.05 ). Conclusion Tetramethylpyrazine can antagonize the cochlear injury induced by cisplatin in guinea pigs, which may be related to the removal of oxygen free radicals, microcirculation and anti-apoptosis in cochlear.