| Background: The inner ear had been known as an organ exempted from immune system for lack of immunocytes in the past. However, recent researches have shown that the lymphocytes and immunocompetent cells resident around peri-endolymphatic sac and the inner ear comes under the immuno-surveillance of the immune system. So the labyrinthitis or immunological response may be occurred rapidly in cochleae after antigenic stimulus. Nuclear transcription factor κBκNF-κB), a sort of important transcription activator, may play an important role in inflammatory reaction. The inflammatory lesion would occur if NF-κB was activated excessively. These conclusions indicated that the labyrinthitis induced by otitis media may be related with the overactivation of NF-κB. Our research is to find out the relationship between labyrinthitis and NF-κB through identifying the changes of NF-κB p65 and the messenger ribonucleic acid κmRNA) of tumor necrosis factor-α κTNF-α) and interleukin-2 κIL-2) in labyrinthitis. The results may offer some theoretical foundation to prevent or cure inner ear dysfunction caused by inflammatory lesion.Methods1. Establishing animal model of labyrinthitis: Forty-eight pigmented guinea pigs were randomly allocated into four groups: LPS 0.01mg/ml group, LPS 0.1mg/ml group, LPS 1mg/ml group and control group. In three experimental animals, different concentrations κ0.01, 0.1, or 1.0 mg/ml) of LPS were transtympanically injected respectively, while the equal volume of saline was used in control group. And auditory brain stem responses κABR) were recorded at 6 hours, 48 hours and 2 weeks later. Then the detected animals were killed. The morphology changes of cochlea of those guinea pigs were observed through light microscope and electron microscope. Finally, the suitable concentration of LPS inducing labyrinthitis was selected.2. Identifying NF-κB p65, TNF-α mRNA and IL-2 mRNA in animal model: Forty-two pigmented guinea pigs were randomly allocated into three groups: ①LPS 1mg/ml group injected transtympanically by LPS κ1mg/ml). ② Pyrrolidine dithiocarbamateκPDTC)treatment group: PDTC was injected intraperitoneally before giving LPS in this group. ③ Control group injected by saline. Those animals were killed after detecting ABR at 6 hours, 48 hours and 2 weeks later. Then the expressions of NF-κB p65, TNF-α mRNA and IL-2 mRNA in these cochlea were investigated by the technique of immunohistochemistry κIHC) or in-situ hybridization histochemistry κISHH). Results 1. Influence of different LPS concentration on guinea pigs' cochlea: The different effect on ABR threshold and pathomorphology of cochlea changed with different concentration of LPS κ0.01 mg/ml, 0.1 mg/ml, 1mg/ml)in these guinea pigs. The ABR threshold increased and labyrinthitis were occurred in the concentration of 1.0 mg/ml group at 6 hours and 48 hours, which returned to a normal level at 2 weeks later, while it had no fluctuation in 0.01 and 0.1 mg/ml LPS groups.2. Expression of NF-κB p65: NF-κB p65 was normally expressed mainly in I type fibrocyte of spiral ligamentκSL). More regions, such as five type fibrocytes and root cell of SL, spiral ganglion cells κSGC), spiral modiolar veinκSMV) and Corti's organ, were stained at 6 hours and 48 hours in LPS group, in which the staining of nuclei were stronger than that of cytoplasm. Furthermore, the expression of NF-κB p65 at 48 hours is more obvious than that at 6 hours, then it decreased to normal at 2 weeks.3. Expression of TNF-α mRNA: TNF-α mRNA wasn't expressed in the general guinea pig cochlea. At 6 hours after LPS stimulation, TNF-α mRNA was expressed at SGC, Corti's organ and spiral limbus, while some weak positive cells were observed in stria vascularis κStV), SL and SMV. The immunostaining was more signiticant at 48 hours than that at 6 hours. However, only SGC was weak stained at 2 weeks.4. Expression of IL-2 mRNA: In normal guinea pig cochlea, expression of IL-2 mRNA can't be viewed. The positive staining was observed in SGC and spiral lim...
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