摘要：目的 探討經圓窗膜局部應用地塞米松對放射性內耳損害的保護作用,為頭頸部腫瘤放療所致內耳損害的預防和治療提供理論依據.方法 選取130只豚鼠隨機分為4組:(1)地塞米松組(45只):對豚鼠右耳進行70 Gy ~(60)Co γ線照射后,經圓窗膜給地塞米松1次;(2)單純照射組(45只):對豚鼠右耳進行70 Gy ~(60)Co γ線照射;(3)鹽水對照組(30只):對豚鼠右耳進行70 Gy ~(60)Co γ線照射后,經圓窗膜給生理鹽水1次;(4)健康對照組(10只):不做任何處理.前3組動物在實驗前、照射(給藥)后第3天、第2周、第2個月后,分別檢測聽覺腦干反應(ABR),各組動物均觀察中耳黏膜,鋪片及掃描電鏡觀察耳蝸毛細胞的形態學變化.結果 ABR閾值正常值為(8.2±2.8)dB,經照射后的3組實驗動物ABR閾值均較正常值升高并呈隨時間推移逐漸升高的趨勢.ABR閾值在第3天、第2周和第2個月的時間段,地塞米松組分別是:(24.0±14.1)、(27.1±9.9)和(38.0±15.1)dB;單純照射組分別是:(24.5±13.5)、(39.5±15.4)和(57.2±18.4)dB;鹽水對照組分別是:(27.0±14.6)、(42.8±13.5)dB(本組僅觀察第3天和第2周).其中,地塞米松組在術后第2周和第2月ABR閾值較其他兩組降低,差異具有統計學意義(P<0.05).在基底膜鋪片和掃描電鏡下觀察中,健康對照組外毛細胞缺失為(8.0±2.7)個,內毛細胞缺失為(3.7±1.2)個.照射后的3組動物的內、外毛細胞的缺失數量均有明顯增加,且外毛細胞多于內毛細胞.各組均表現為隨時間推移缺失數逐漸增加的趨勢.在術后第2周和第2個月,地塞米松組比單純照射組的外毛細胞缺失個數減少,分別為(30.7±7.6)與(60.3±14.5)和(67.3±7.0)與(100.0±5.3),兩者的差異均有統計學意義(P<0.05).掃描電鏡觀察發現,照射后耳蝸毛細胞表現為纖毛倒伏,融合或缺失其中以第3排外毛細胞為重,并隨時間推移而加重.地塞米松組的毛細胞損害在第3天和第2周較其他組輕,但在第2個月時沒有明顯差異.結論 經圓窗膜給地塞米松可以在一定的程度上減輕大劑量放射所造成的豚鼠的內耳損害.%Objective To investigate the protective effect of dexamethasone applied to round window membrane (RWM) against radiation-induced inner ear damage in guinea pigs, in order to provide the evidence for preventing and treating radiation-induced inner ear damage. Methods 130 guinea pigs were randomly divided into four groups. (1) Dexamethasone group( n = 45): The guinea pigs were injected with dexamethasone through an intact RWM on right ear for one time after being treated with 70 Gy ~(60)Co γ irradiation. (2) Irradiation group(n = 45) : The guinea pigs were treated with 70 Gy ~(60)Co γ irradiation. (3) Saline group (n = 30): Applying of normal saline through an intact RWM on right ear for one time after being treated with 70 Gy ~(60)Co γ irradiation. (4) Control group(n =45) : Auditory brainstem response (ABR) was tested before the 3 rd day, the second week and the second month after irradiation (treatment) in the first three groups. The animals were sacrificed right after the ABR test and the middle ear mucosa was observed simultaneously. The hair cells were observed by surface preparation of the basilar membrane and scanning electron microscope ( SEM). ResultsThe normal ABR threshold is (8.2 ±2.8) dB. The ABR thresholds increased in those of the three groups treated with irradiation and were rising with time. At the 3rd day, the second week and the second month, ABR thresholds of the dexamethasone group were (24.0 ± 14.1), (27.1±9.9) and (38.0 ± 15.1) dB, respectively, while the irradiation group were (24.5 ± 13.5), (39.5 ± 15.4) and (57.2 ± 18.4) dB. The saline group were (27.0 ± 14.6) and (42.8 ± 13.5) dB, respectively. ABR thresholds of the dexamethasone group at the second week and the second month both decreased compared with those of the irradiation group and saline group ( P < 0.05) . In the control group, the outer hair cell lost by 8.0 ± 2.7 and inner hair cell by 3.7 ± 1.2. The lost quantities of the inner hair cells and outer hair cells were decreased significantly in the three groups with irradiation, and outer hair cells were more than inner hair cells. The loss of hair cells was increased gradually in all groups with irradiation. At the second week and the second month, the loss of outer hair cells in the dexamethasone group were less than those in irradiation group, which were 30.7±7.6 vs. 60.3 ± 14.5 and 67.3 ± 7.0 vs. 100.0 ±5.3 (P < 0.05) . The SEM showed the fusion, loss, lodging and other pathological changes in stereociliary bundle and the losses of hair cell, which were more serious. Those of pathological changes in the dexamethasone group were weaker than those in the groups with irradiation at the 3rd day and the second week. Conclusions Application of dexamethasone through intact RWM could reduce the extent of radiation-induced inner damage.
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