鼓室内注射川芎嗪改善顺铂诱导耳毒性大鼠模型作用机制研究OA

Objective To explore the mechanism of intratympanic injection of tetramethylpyrazine(TMP)in intervention of cisplatin induced ototoxicity in rats.Methods The experimental rats were divided into blank control group(group B),blank+tympanic injection TMP group(group B+L),model control group(group M),and model+tympanic injection TMP group(group M+L).Auditory brainstem response was used to detect hearing changes in rats;Using cochlear basement membrane preparation to detect the pathological changes in rat cochlear hair cells;The colorimetric method was used to detect the levels of nitric oxide(NO),hydrogen peroxide(H2O2),and malondialdehyde(MDA)in rat serum,as well as the activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px);Western blot was used to detect the expression of cytoplasmic nuclear factor erythroid 2-related factor 2(Nrf2),nuclear Nrf2,heme oxygenase-1(HO-1),gamma glutamylcysteine synthase(γ-GCS)protein in rat cochlear tissue;RT-qPCR was used to detect the mRNA levels of Nrf2,HO-1,and γ-GCS in rat cochlear tissue.Results Compared with group B,the hearing threshold of rats in group M increased,hair cells were lost,the content of NO in serum decreased,the contents of H2O2 and MDA increased,the activity of antioxidant enzymes decreased,the expression of Nrf2 protein in the cytoplasm of cochlear tissue increased,and the expressions of Nrf2,HO-1 and γ-GCS proteins in the nucleus significantly decreased(P<0.05).Compared with group M,the hearing threshold of rats in group M+L decreased,the loss of hair cells was alleviated,the content of NO in serum increased,the contents of H2O2 and MDA decreased,the activity of antioxidant enzymes increased,the expression of Nrf2 protein in the cytoplasm of cochlear tissue decreased,and the expressions of Nrf2,HO-1 and γ-GCS proteins in the nucleus significantly increased(P<0.05).Conclusion Intratympanic injection of TMP can promote Nrf2 nuclear translocation,increase the expression of HO-1 and γ-GCS proteins,and alleviate cisplatin induced ototoxicity by regulating the Nrf2/antioxidant response element(ARE)signaling pathway.