Effect Of Cisplatin On Expression Of TRPA1and TRPV1in Mouse Cochlea

ObjectiveTo investigate the effect of cisplatin on expression of transient receptorpotential channel protein A1(TRPA1) and transient receptor potential channelprotein V1(TRPV1) in mouse cochlea, and to explore the possible role ofTRPA1and TRPV1in cisplatin-induced hearing loss, so as to provide newmethod and theoretical evidence for the therapy of cisplation ototoxicity.Methods70healthy BALB/c mice were randomly divided to control group, cisplatin2.5mg/kg group, cisplatin3.5mg/kg group, cisplatin4.5mg/kg group andcisplatin5.5mg/kg group, each group was14mice. Mice were injectedintraperitoneally for5days, and once a day. Immunofluorescent staining andimaging analysis technique and western blotting were used to detect theexpression of TRPA1and TRPV1in mouse cochlea. At the same time,auditory brainstem response (ABR) was measured to observe the change ofhearing.Results1.After injected intraperitoneally for5days, ABR threshold shifts indifferent concentration of cisplatin groups were significantly amplified at eachstimulating frequency as compared with control group (P<0.01), and increasedremarkably with more injected cisplatin (P<0.01). It showed that there was adose-effect relationship between them.2. The results of immunofluorescent staining and imaging analysis showed that TRPA1and TRPV1were both weak expression in outer hair cell,spiral ganglion and stria vascularis of cochlea in control group. The expressionof TRPA1and TRPV1in above positions in different concentration of cisplatingroups were greater than that in control group (P<0.05, P<0.01). However, theexpression of TRPA1was no obvious difference among cisplatin groups, whilethe expression of TRPV1was increased remarkably with more concentrationof cisplatin (P<0.05, P<0.01).3. The results of western blotting and semi-quantitative analysis showedthat the protein expression levels of TRPA1and TRPV1were very low incontrol group. The protein expression levels of TRPA1and TRPV1in differentconcentratin of cisplatin groups were greater than those in control group(P<0.05, P<0.01). However, the protein expression level of calpain1was nosignificant difference among cisplatin groups, while the protein expressionlevel of calpain2were greater remarkably with more concentration of cisplatin(P<0.05, P<0.01).ConclusionsThere was a little expression of TRPA1and TRPV1in the cochlea ofnormal mouse. Cisplatin could increase the expression of TRPA1and TRPV1in the mouse cochlea, and the expression of TRPV1gradually increased withmore concentration of cisplatin. These suggested that TRPA1and TRPV1might be involved in cisplatin-induced ototoxicity, and TRPV1might play aleading role in cisplatin-induced ototoxic injury.