| Objective: Diabetes Mellitus(DM) is a chronic metabolic disease inwhich high blood glucose is the key feature due to interacted various factors.With the development of social economy and anging of population,theprevalence rate of DM is rising year by year. All of type2DM patients areabout90%, and the chronic complications of DM severely effect quality of lifefor people. Scine the first report of diabetes hearing loss by Jordao in1857, itwas aroused wide attention and was studied largely.Now there are severalresearch trend about the pathogenesis of diabetes hearing loss: vasculopathy,neuropathy, dysbolism, genetics,et al.Though a lot of studies indicate that thedamage of hair cells finally result in hearing impairment, it is still indefinitefor the concrete mechanism of the damage of hair cells. In recent years somestudies show that Gap Junction Channel in inner ear is the bridge of theexchange of communication and material among groups of cells, to ensurehigh K+concentration and homeostasis of endolymph, finally accomplishvoice signals’ transmission function of cochlear. Cx26and Cx30are the mainConnexins proteins that make up Gap Junction Channel. The hearing loss isreported to be predominantly high-frequency in patients with Cx26and Cx30mutation, and this is similar to the diabetes hearing loss. Tthe physiologymechanism of deafness linked Cx26and Cx30mutation may be caused bydecreased of quantity of Gap Junction Channels of Cx26and Cx30, it effectsthe high K+concentration and homeostasis of endolymph, lead to hair cellsdenaturation, and result in hearing impairment. Now there is no study that howare the expression of Cx26and Cx30of type2diabetes mellitus in thecochlear, and whether there is a relationship between the Cx26and Cx30andhearing change. The model of type2diabetic rat was established in the experimention,and observed hearing changes by the auditory brainstem response, detectedexpression level change of the Cx26and Cx30in different term with HE andinnmnofluorescence staining among normal and type2diabetic rats. It isdiscusseded whether the roles of Cx26and Cx30is important of thedevelopment process of type2diabetes mellitus hearing loss.Methods:60male Wistar rats, weighing170-190g, were randomlydivided into two groups after1week feeding: control group(n=20),experimental group(n=40). The control group were fed with normal feedstuffwhile experimental group were fed with high-sugar-fat feedstuff for8weeks.Both groups’ rats were fasted overnight for12hours, type2diabetes wasinduced by injected intraperitoneally30mg/Kg of streptozotocin(STZ), controlgroup injected the same dose of citrate-buffer solution. At the end of the9thweek, rats with fasting blood glucose(FBG) more than7.8mmol/L wereconsidered as T2DM. The weights, FBG and urine glucose levels of all theanimals were measured, and the activity,feeding, urine, hair gloss and earresponse of all the animals were also observed at4,8,12,16and20weeks aftermodeling. Click-evoked ABR were measured for all animals at4,8,12,16and20weeks after modeling and before modeling. After the test of ABR,theanimals were group by group anesthetized,implanted, and decapitated, thenthe cochlear were taked out of. Through HE staining and innmnofluorescencestaining of the cochlear we could observe morphology and the changes ofCx26and Cx30of cochlear. The measured data were presented as mean±standard deviation.Two sample means were analysised using independentsamples t-test or nonparametric test. Statistical significance was determined atp <0.05.Results:1General observations:In the course of experiment, the rats of T2DM groups showed polyphagia,polydipsia, polyuria.With the development of T2DM the rats appeared somesymptoms: furs were filthy and reduced, growth slowly, activities decreased, insensitive response to ear, et al. The rats of control group didn’t show diabeticsymptoms, their growth and nurtures were well.2Changes in weight:The body weight of the rats had no difference between two groups at the0and4weeks after modeling. The body weight of rats in T2DM wasdecreased than that in control group at the time of8,12,16and20weeks aftermodeling(P<0.01).3Changes in FBG and urine:The FBG and urine of rats had difference between two groups at the4,8,12,16,20weeks after modeling(P<0.01): the FBG of T2DM group wasalways＞7.8mmol/L, the FBG of control group was always＜7.8mmol/L; theurine of test group was always＋＋＋＋，urine of control group was alwaysnegative.4Chronological ABR changes:Throught the experiment the thresholds of click-evoked ABR in eachgroup did not differ among groups（P<0.05）. ABR latencies of Ⅰ,Ⅲ,Ⅴwavesand ABR interpeakⅠ-Ⅲ, Ⅲ-Ⅴ, Ⅰ-Ⅴ latencies between test group andcontrol group had no difference at the0and4th week after modeling（P>0.05）.Compared with the control group, the test group exhibited delayed waves IIIand Ⅴlatency and prolonged interpeak Ⅰ-Ⅲ andⅠ-Ⅴ latencies at the8th,12th,16th,20th week(P<0.05).5HE staining:Compared with the control group, the amount of lumens in the striavascularis were less in the test group, and the amount of spiral ganglion cellsand the cells of spiral ligament were less in test group（P<0.05）.6The expression of Cx26and CX30in rat cochlear:The fluorescence intensity of Cx26and Cx30in the basement membrance,stria vascularis and spiral ligament between test group and control group hadno difference at the4th week （P>0.05）, but had difference at the8th,12th,16th,20th （P<0.05）.Conclusions: 1Type2diabetic rat model which can be used as type2diabetes hearingloss model for study was induced by high-sugar-fat feedstuff and small dose ofSTZ injection.2The type2diabetic rats had hearing impairment in the early stage, ABRcan be used to diagnose hearing loss as one of the indicators.3Type2diabetes hearing impairment was possibly associated with Cx26and Cx30. |
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