中国临床药理学杂志

目的 观察耳后注射地塞米松磷酸钠注射液治疗突发性聋的临床疗效和安全性。方法 将突发性聋患者根据治疗方法分为对照组与试验组。2组均参照指南进行常规治疗(神经营养、微循环改善)，对照组在常规治疗基础上采用甲泼尼龙琥珀酸钠80 mg，静滴，1日1次，连用4 d，减为40 mg，再用4 d，减为20 mg，再用2 d;试验组在对照组基础上给予耳后注射地塞米松磷酸钠注射液5 mg，每隔1日进行1次注射，2组均治疗10 d。比较2组患者的疗效、代谢组学差异、听力恢复情况、血液流变学指标、免疫功能指标并进行安全性评价。结果对照组纳入38例，试验组纳入42例。治疗后，试验组治疗有效率为80.95%(34例/42例)高于对照组的57.89%(22例/38例)，2组比较在统计学上差异具有统计学意义(P<0.05)。突发性聋治疗前共有11种代谢物显著升高，18种代谢物显著降低;其中升高最多的4种代谢物是抗坏血酸、牛磺熊脱氧胆酸、D-泛酸、葡萄糖二酸，降低最多的代谢物为溶血磷脂酰乙醇胺、香草酸。在对突发性聋患者进行治疗后，突发性聋治疗后有效组较无效组共有37种代谢物显著升高，8种代谢物显著降低;升高最多的3种代谢物是L-亮氨酸、十一烷酰基肉碱、月桂烯酰肉碱，降低最多的3种代谢物为L-组氨酸、2-吡啶基乙酸、D-泛酸。治疗后，对照组和试验组在0.5 k Hz下的听阈值分别为(49.82±7.03)和(43.69±5.38) d B,1.0 k Hz下的听阈值分别为(58.14±7.39)和(46.33±6.25)d B,2.0 k Hz下的听阈值分别为(60.05±8.23)和(49.51±5.30) d B,4.0 k Hz下的听阈值分别为(62.29±8.14)和(51.36±5.87) d B;超氧化物歧化酶(SOD)分别为(94.65±14.06 )和(99.72±13.56 )μg·L^-1;丙二醛(MDA)分别为(4.36±0.51)和(3.94±0.40)μmol·L^-1;两组血浆黏度分别为(2.12±0.30)和(1.55±0.26) m Pa·s;红细胞聚集指数分别为3.38±0.30和2.97±0.19;低切黏度分别为(10.13±1.60)和(9.06±1.19) m Pa·s;高切黏度分别为(5.96±0.39)和(5.33±0.31) m Pa·s; 2组分化抗原簇(CD) 3⁺分别为57.76±4.70和63.52±5.46; CD4⁺分别为33.29±3.38和37.42±3.68,CD4⁺/CD8⁺分别为1.43±0.22和1.70±0.30;免疫球蛋白(Ig ) G分别为(12.16±1.12)和(10.23±0.93 ) g·L^-1,Ig A分别为(2.36±0.23 )和(2.11±0.15) g·L^-1，上述指标在2组间比较，在统计学上差异均有统计学意义(均P<0.05)。2组治疗期间均未发生显著不良反应。结论 采用耳后注射地塞米松磷酸钠注射液治疗突发性聋具有显著效果，其在改善代谢组学差异、血液流变学及免疫功能方面具有优势，值得临床推广。

Objective To observe the clinical efficacy and safety of retroauricular injection of dexamethasone sodium phosphate injection in the treatment of sudden deafness. Methods Patients with sudden deafness were divided into control group and treatment group according to actual treatment method. Both groups were given conventional treatment(neurotrophy and microcirculation improvement) according to guidelines. The control group received additional intravenous drip of methylprednisolone sodium succinate(80 mg once daily for 4 d,reduced to 40 mg for 4 d,then further reduced to 20 mg for 2 d). The treatment group was given retroauricular injection of dexamethasone(5 mg every other day) in addition to the control group's regimen. Both groups were treated for 10 d.The efficacy,metabolomic differences,hearing recovery status,hemorheological indexes,and immune function indexes were compared between the two groups. Meanwhile,the safety was evaluated. Results 38 cases and 42 cases were included in the control group and the treatment group,respectively. After treatment,the effective rates in the treatment group and the control group were 80. 95%(34 cases/42 cases) and 57. 89%(22 cases/38 cases),with statistically significant difference(P < 0. 05). There were significant increases in 11 metabolites and significant decreases in 18 metabolites before treatment for sudden deafness. The four metabolites showing the most significant increases were ascorbic acid,tauroursodeoxycholic acid,D-pantothenic acid,and glucaric acid. The most significantly decreased metabolites were lysophosphatidylethanolamine and vanillic acid. After treatment,patients with sudden deafness in the effective group showed significant increases in 37 metabolites and significant decreases in 8 metabolites compared to the ineffective group. The three metabolites showing the most significant increases were L-leucine,undecanoylcarnitine,and lauroylcarnitine,while the three with the most notable decreases were L-histidine,2-pyridylacetic acid,and D-pantothenic acid. After treatment,hearing thresholds under 0. 5,kHz in the control group and the treatment group were(49. 82 ± 7. 03) and(43. 69 ± 5. 38) d B,respectively; hearing thresholds under 1. 0 k Hz were(58. 14 ± 7. 39)and(46. 33 ± 6. 25) dB,respectively; hearing thresholds under 2. 0 kHz were(60. 05 ± 8. 23) and(49. 51 ± 5. 30)dB,respectively; hearing thresholds under 4. 0 k Hz were(62. 29 ± 8. 14) and(51. 36 ± 5. 87) dB,respectively,with statistically significant differences between two groups(P < 0. 05). After treatment,superoxide dismutase(SOD)levels in the control group and the treatment group were(94. 65 ± 14. 06) and(99. 72 ± 13. 56) μg · L^-1;malondialdehyde(MDA) levels were(4. 36 ± 0. 51) and(3. 94 ± 0. 40) μmol · L^-1,with statistically significant differences between groups(P < 0. 05). After treatment,plasma viscosity in the control group and the treatment group was(2. 12 ± 0. 30) and(1. 55 ± 0. 26) m Pa·s; erythrocyte aggregation index was 3. 38 ± 0. 30 and 2. 97 ± 0. 19; low-shear viscosity was(10. 13 ± 1. 60) and(9. 06 ± 1. 19) m Pa ·s; high-shear viscosity was(5. 96 ± 0. 39) and(5. 33 ± 0. 31) m Pa·s,with statistically significant differences between groups(P < 0. 05). After treatment,CD3~+in the control group and the treatment group was 57. 76 ± 4. 70 and 63. 52 ± 5. 46; CD4~+was 33. 29 ± 3. 38 and37. 42 ± 3. 68; CD4⁺/CD8~+was 1. 43 ± 0. 22 and 1. 70 ± 0. 30; immunoglobulin(Ig) G levels were(12. 16 ± 1. 12)and(10. 23 ± 0. 93) g·L^-1; IgA levels were(2. 36 ± 0. 23) and(2. 11 ± 0. 15) g·L^-1,with statistically significant differences between groups(all P < 0. 05). No significant adverse reactions occurred in either group during the treatment. Conclusion Retroauricular injection of dexamethasone sodium phosphate injection is markedly effective in the treatment of sudden deafness,and it has advantages in improving metabolomic differences,hemorheology and immune function.