川芎嗪干预顺铂致聋大鼠中对Beclin1及LC3影响的实验研究  

Experimental Study on Effect of Tetramethylpyrazine on Beclin1 and LC3 in Rats with Cisplatin-Induced Deafness

作　　者：冷辉[1] 潘玉真[1] 石磊[1] 王爱平[1] 张琦[1] LENG Hui;PAN Yuzhen;SHI Lei;WANG Aiping;ZHANG Qi(The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)

机构地区：[1]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《中华中医药学刊》2022年第12期13-16,I0027,共5页Chinese Archives of Traditional Chinese Medicine

基　　金：辽宁省教育厅项目(L201901)。

摘　　要：目的通过构建川芎嗪(tetramethylpyrazine,TMP)干预治疗顺铂(cis-Dichlorodiammine platinum,DDP)所诱导的药物性聋大鼠的实验研究,探讨实验中自噬蛋白Beclin1及LC3的变化情况。方法随机将110只SD大鼠分成为空白组45只和模型组65只,分别采用腹腔注射盐水和顺铂塑造模型,各组随机选取5只进行模型评定,将余下的100只大鼠等分成为盐水组、盐水+TMP组、顺铂组、顺铂+TMP组和抑制剂组,盐水组大鼠腹腔注射盐水;盐水+TMP组大鼠腹腔注射盐水和TMP;顺铂组大鼠腹腔注射DDP;顺铂+TMP组大鼠腹腔注射DDP和TMP;抑制剂组大鼠腹腔注射DDP和自噬抑制剂3-MA。末次给药后,采集耳蜗样本,通过免疫组化和Western blot法检测各组大鼠耳蜗组织中Beclin1及LC3蛋白表达水平。结果在免疫组化的检测川芎嗪对顺铂所致药物性聋大鼠耳蜗组织中Beclin1及LC3的结果中显示,与盐水组比较,除抑制机组外,其余各组Beclin1及LC3蛋白表达量增强(P<0.01);与顺铂组比较,顺铂+TMP组蛋白表达量增强(P<0.01)而抑制剂组蛋白表达量则降低(P<0.01)。在Western blot检测结果川芎嗪对顺铂所致药物性聋大鼠耳蜗组织中Beclin1及LC3的结果中显示:与盐水组和盐水+TMP组比较,顺铂组和顺铂+TMP组Beclin1及LC3蛋白表达量增强(P<0.01);与顺铂组比较,顺铂+TMP组蛋白表达量增强(P<0.01)而抑制剂组蛋白表达量则降低(P<0.01)。结论在川芎嗪干预顺铂致聋大鼠中,川芎嗪可调控自噬蛋白Beclin1表达下降,自噬蛋白LC3表达上升。川芎嗪能够治疗顺铂诱导的药物性聋的作用机制可能与川芎嗪能促进自噬有关。Objective To construct tetramethylpyrazine(TMP)intervention to treat deafness induced by cis-dichlorodiammine platinum(DDP)in rats.To investigate the changes of autophagic proteins Beclin1 and LC3 in the experiment.Methods A total of 110 SD rats were divided into blank group(45 rats)and model group(65 rats).The intraperitoneal injection of saline and cisplatin were used respectively.Five rats in each group were randomly selected for model evaluation.The remaining 100 rats were equally divided into saline group,saline+TMP group,cisplatin group,cisplatin+TMP group and inhibitor group.Rats in saline group were intraperitoneally injected with saline.Rats in saline+TMP group were intraperitoneally injected with saline and TMP.DDP was intraperitoneally injected into rats in cisplatin group.DDP and TMP were intraperitoneally injected into rats in cisplatin+TMP group.Rats in the inhibitor group were intraperitoneally injected with DDP and autophagy inhibitor 3-MA.After the last administration,the cochlea samples were collected and the expression levels of Beclin1 and LC3 proteins in the cochlea tissues of rats in each group were detected by immunohistochemistry and Western blot methods.Results The results of immunohistochemistry of Beclin1 and LC3 in the cochlea of rats with cisplatin-induced deafness induced by tetramethylpyrazine showed that compared with those of the saline group,the protein expressions of Beclin1 and LC3 in the rest groups increased(P<0.01).Compared with those of the cisplatin group,the protein expressions of cisplatin+TMP group increased(P<0.01),while the protein expressions of inhibitor group decreased(P<0.01).Western blot analysis showed that the expressions of Beclin1 and LC3 protein in the cochlea of cisplatin induced deafness rats were increased in cisplatin group and cisplatin+TMP group compared with those of saline group and saline+TMP group(P<0.01).Compared with those of the cisplatin group,the protein expressions of cisplatin+TMP group increased(P<0.01),while the protein expressions of inhi

关 键 词：川芎嗪 顺铂 自噬 BECLIN1 LC3 

分 类 号：R282.71[医药卫生—中药学]