Objective: The susceptibility of tinnitus rats with low estrogen level induced by sodium salicylate and the changes of tumor necrosis factor α (TNF-α) in serum were observed to investigate the relationship between tinnitus occurrence and estrogen level. Methods: Forty-two healthy female Wistar rats were randomly divided into control group(n=6), normal group(n=6), sham operation group(n=6) and ovariectomized group(n=24). Control group was intraperitoneally injected with normal saline 200 mg/kg for 14 consecutive days. Normal group, sham operation group and ovariectomized group were intraperitoneally injected with sodium salicylate 200 mg/kg for 14 consecutive days. Before and after sodium salicylate induction, the tinnitus behavior of rats in each group was detected by prepulse inhibition (PPI) and gap pre-pulse inhibition of the acoustic startle (GPIAS) test. Before and after sodium salicylate induction, blood samples were collected from eyeballs of rats in each group, and serum levels of estradiol and TNF-α were detected by ELISA. SPSS 25.0 software was used to analyze the data. Results: (1) Following 14 days of sodium salicylate intervention, there was no significant difference in PPI inhibition rate between groups or within groups(all P>0.05). (2)There was no significant difference in the inhibition rate of GPIAS in the four groups before sodium salicylate injection(F=0.217, P>0.05). With sodium salicylate injected for 14 days, the inhibition rate of GPIAS in ovariectomized group (30.88%±15.40%) was significantly lower than that in the other three groups (44.11%±21.06%, 38.27%±10.92%, 51.59%±11.34%), and the difference was statistically significant(F=3.533, P<0.05). The inhibition rate of GPIAS in ovariectomized group with sodium salicylate injected for 14 days was significantly lower than that before injection, and the difference was statistically significant(t=2.977, P<0.05).There was no significant difference in GPIAS inhibition rate between the other three groups before and after sodium salicylate injection(P>0.05). (3)The level of TNF-α in ovariectomized rats was significantly higher than that in the other three groups, the difference was statistically significant(all P<0.05). With sodium salicylate injection for 14 days, TNF-α level in the ovariectomized group increased more significantly than that in the other three groups, the difference was statistically significant(F=8.045, P<0.05). TNF-α levels increased following salicylate injection in normal group, sham operation group and ovariectomized group, and the differences were statistically significant(t value was -4.843, -4.932 and -5.965 respectively, each P<0.05). There was no significant difference in TNF-α levels before and after normal saline injection in control group(all P>0.05). Conclusion: Low estrogen levels increase susceptibility to sodium salicylate-induced tinnitus. Decreased estrogen levels may increase susceptibility to tinnitus through the increased expression of pro-inflammatory factor TNF-α.
目的： 通过观察水杨酸钠诱导低雌激素状态耳鸣大鼠模型的易感性及血清TNF-α的变化，探讨耳鸣发生与雌激素水平的关系。 方法： 健康Wistar 雌性大鼠42只，随机数字表法分为空白对照组（6只）、正常大鼠组（6只）、假手术组（6只）、卵巢去势组（24只）。空白对照组予生理盐水200 mg/kg腹腔注射，连续注射14 d；正常大鼠组、假手术组、卵巢去势组予水杨酸钠200 mg/kg腹腔注射，连续注射14 d。于水杨酸钠诱导前后采用惊跳反射前脉冲抑制（prepulse inhibition，PPI）和听觉惊跳反射前刺激抑制（gap pre-pulse inhibition of the acoustic startle，GPIAS）试验检测各组大鼠的耳鸣行为。于水杨酸钠诱导前后将4组大鼠眼球取血，采用ELISA法检测各组大鼠血清雌二醇、TNF-α水平。采用SPSS 25.0软件进行统计学分析。 结果： 水杨酸钠干预14 d前后，4组大鼠PPI抑制率组间比较、组内比较差异均无统计学意义（P值均>0.05）。水杨酸钠注射前4组大鼠GPIAS抑制率差异无统计学意义（F=0.217，P>0.05）；水杨酸钠注射14 d后，卵巢去势组GPIAS抑制率为（30.88±15.40）%，其余3组分别为（44.11±21.06）%、（38.27±10.92）%、（51.59±11.34）%，差异有统计学意义（F=3.533，P<0.05）。卵巢去势组GPIAS抑制率在水杨酸钠注射14 d后明显低于注射前，差异有统计学意义（t=2.977，P<0.05）；其余3组水杨酸钠注射前后GPIAS抑制率差异均无统计学意义（P值均>0.05）。卵巢去势组在大鼠卵巢去势后，TNF-α水平明显高于其余3组，差异有统计学意义（F=5.060，P<0.05）；水杨酸钠注射14 d后，卵巢去势组的TNF-α水平上升更明显，高于其余3组，差异有统计学意义（F=8.045，P<0.05）。正常大鼠组、假手术组、卵巢去势组水杨酸钠注射后TNF-α水平升高，差异均有统计学意义（t值分别为-4.843、-4.932、-5.965，P值均<0.05）；空白对照组生理盐水注射前后TNF-α水平差异无统计学意义（t=1.142，P>0.05）。 结论： 低雌激素水平使水杨酸钠诱导耳鸣的易感性增加。雌激素水平下降，可能通过促炎因子TNF-α表达上升增加耳鸣的易感性。.