连翘酯苷对顺铂致豚鼠耳毒性的影响及其机制探讨

Effect of forsythiaside on cisplatin-induced ototoxicity of guinea pigs

目的探讨连翘酯苷对顺铂致豚鼠耳毒性的影响及其机制。方法 30只豚鼠随机分为对照组、顺铂组和连翘酯苷组,每组各10只。顺铂组豚鼠腹腔注射顺铂溶液8 mg/(kg·d),连续7 d;连翘酯苷组在每次注射顺铂溶液30 min前腹腔注射连翘酯苷25.0 mg/(kg·d),连续7 d;正常对照组以生理盐水代替顺铂溶液腹腔注射,连续7 d。实验动物被处死前,检测其畸变产物耳声发射(DPOAE)幅值变化;采用免疫组化SP法和Western blot法检测各组豚鼠耳蜗组织bcl-2蛋白的表达。结果 1、2、4、6、8 kHz测试频率下,3组DPOAE幅值比较差异均有统计学意义(P均<0.05),即顺铂组<连翘酯苷组<对照组。3组豚鼠耳蜗组织bcl-2蛋白表达比较差异均有统计学意义(P<0.05或<0.01),即顺铂组<连翘酯苷组<对照组。结论连翘酯苷可减轻顺铂所致耳蜗损伤,上调耳蜗组织bcl-2蛋白表达可能是其作用机制之一。

Objective To study the effect of forsythiaside on cisplatin-induced ototoxicity of guinea pigs. Methods Thirty guinea pigs were randomly divided into the control group （n = 10）, cisplatin group （n = 10） and forsythiaside group （n = 10）. The guinea pigs in the cisplatin group were induced by intraperitoneal injection of cisplatin solution （8 mg/kg per day） for 7 days, the guinea pigs in the forsythiaside group were given forsythiaside （25 mg/kg per day） at 30 min before cisplatin solution for 7 consecutive days, and the normal saline instead of cisplatin was injected in the control group. The distortion product otoacoustic emission （DPOAE） was detected before the experimental animals were killed, and the expression of bcl-2 in cochlea of guinea pigs was detected by immunohistochemistry and Western blotting. Results Statis- tical difference was found in the DPOAE amplitudes under 1,2, 4, 6 and 8 kHz test frequencies among the three groups ： cisplatin group 〈 forsythiaside group 〈 control group （ all P 〈 0.05）. Meanwhile, statistical difference was found in the expression of bcl-2 protein among the three groups ： cisplatin group 〈 forsythiaside group 〈 control group （ P 〈 0.05 or P 〈 0.01 ）. Conclusion Forsythiaside can significantly reduce the eisplatin-indueed ototoxieity by up-regulating the expression of bcl-2.