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目的:研究川芎嗪对顺铂耳毒性的防护作用。方法:80只听力正常体重250~350g的豚鼠随机分为4组(每组20只豚鼠):生理盐水组、顺铂组、川芎嗪组及川芎嗪+顺铂组。前3组分别腹腔注射生理盐水4ml/(kg·d)、顺铂4mg/(kg·d)、川芎嗪140mg/(kg·d),连续注射6d;第4组在第1、2天腹腔注射川芎嗪140mg/(kg·d),第3天注射川芎嗪后30min,再腹腔注射顺铂4mg/(kg·d),连续注射6d。在给药前及最后1次给药后测定各组豚鼠听觉脑干诱发电位(ABR)阈值的变化。另外,在最后1次给药后测定每组10只豚鼠的耳蜗组织超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,并用透射电镜观察每组另10只豚鼠的耳蜗毛细胞形态的变化。结果:顺铂组、生理盐水组、川芎嗪组及川芎嗪+顺铂组的ABR阈值分别为:(55.652±6.562)dB、(40.556±4.532)dB、(42.321±5.362)dB及(45.639±6.069)dB。顺铂组的ABR阈值明显高于其他3组(P<0.01)。生理盐水组、顺铂组及川芎嗪+顺铂组的SOD活性分别为(33.30±5.89)U/mg、(21.44±6.42)U/mg及(29.69±4.47)U/mg。顺铂组SOD活性明显低于生理盐水组(P<0.01)。川芎嗪+顺铂组SOD活性与生理盐水组比较,差异无统计学意义(P>0.05)。生理盐水组、顺铂组及川芎嗪+顺铂组的MDA含量分别为(10.34±1.74)nmol/mg,(15.72±2.04)nmol/mg及(11.07±1.56)nmol/mg。顺铂组MDA含量明显高于生理盐水组(P<0.01)。川芎嗪+顺铂组MDA含量与生理盐水组比较,差异无统计学意义(P>0.05)。川芎嗪+顺铂组耳蜗毛细胞细胞体及核的形态基本正常;而顺铂组耳蜗毛细胞核染色质固缩、凝集,空泡样变性,组织超微结构损伤明显。结论:川芎嗪对顺铂所致耳毒性有较好的防护作用。
Objective: To study the protective effect of tetramethylpyrazine on cisplatin ototoxicity. Methods: 80 guinea pigs weighing 250-350g were randomly divided into 4 groups (20 guinea pigs in each group): normal saline group, cisplatin group, ligustrazine group and ligustrazine + cisplatin group. The first three groups were injected intraperitoneally with normal saline 4ml/(kg·d), cisplatin 4mg/(kg·d) and tetramethylpyrazine 140mg/(kg·d) for 6 days; the fourth group was intraperitoneally injected on the 1st and 2nd days. Intravenous injection of tetramethylpyrazine 140mg/(kg·d), 30min after the injection of ligustrazine on the third day, and then intraperitoneal injection of cisplatin 4mg/(kg·d), continuous injection 6d. The changes of auditory brainstem evoked potential (ABR) threshold were measured before and after the last dose in each group of guinea pigs. In addition, the activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in the cochlear tissue of 10 guinea pigs in each group were determined after the last administration, and the cochlea hair cells of 10 guinea pigs in each group were observed by transmission electron microscopy. Change in form. Results: The ABR threshold values of cisplatin group, physiological saline group, tetramethylpyrazine group, and tetramethylpyrazine + cisplatin group were (55.652±6.562) dB, (40.556±4.532) dB, (42.321±5.362) dB, and (45.639±) respectively. 6.069) dB. The ABR threshold in the cisplatin group was significantly higher than that in the other three groups (P<0.01). The SOD activities of the normal saline group, cisplatin group, and tetramethylpyrazine + cisplatin group were (33.30±5.89) U/mg, (21.44±6.42) U/mg, and (29.69±4.47) U/mg, respectively. SOD activity in the cisplatin group was significantly lower than that in the saline group (P<0.01). The activity of SOD in ligustrazine plus cisplatin group was not statistically different from that of saline group (P>0.05). The MDA contents in the normal saline group, the cisplatin group, and the tetramethylpyrazine + cisplatin group were (10.34±1.74) nmol/mg, (15.72±2.04) nmol/mg, and (11.07±1.56) nmol/mg, respectively. The MDA content in the cisplatin group was significantly higher than that in the saline group (P<0.01). The content of MDA in the tetramethylpyrazine + cisplatin group was not significantly different from that of the saline group (P>0.05). In the tetramethylpyrazine + cisplatin group, the morphology of the cell body and the nucleus of the cochlea hair cells were almost normal, while in the cisplatin group, the nuclear chromatin of the cochlea was condensed, condensed, vacuolar degeneration, and the ultrastructure of the tissue was significantly damaged. Conclusion: Tetramethylpyrazine has a good protective effect against ototoxicity induced by cisplatin.