KISEP Streptozotocin 으로유발된당뇨병흰쥐에서 Abstract 와우유모세포의형태학적변화 * 정대건 박용수 김상후 김춘일 Morphological Changes of Cochlear Hair Cells in the Streptozotoci

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1 KISEP Streptozotocin 으로유발된당뇨병흰쥐에서 Abstract 와우유모세포의형태학적변화 * 정대건 박용수 김상후 김춘일 Morphological Changes of Cochlear Hair Cells in the Streptozotocin-Induced Diabetic Rat Dae Gun Jung, M.D., Yong Su Park, M.D., Sang Hu Kim, M.D., Chun Il Kim, M.D. Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Catholic University, Seoul, Korea BackgroundDiabetes Mellitus has been known as a multisystemic disorder for a long time. An association between diabetes and hearing loss was first postulated in the one case report published by Jordao in The typical hearing loss from diabetes is a progressive and bilateral sensorineural deficit that predominantly occurs in the high frequency and in the elderly patients. ObjectivesThe purpose of this study was to investigate the morphological changes of cochlear hair cells in the insulin-dependent diabetes mellitus induced by Streptozotocin. Materials and MethodsThirty two rats were used for this study and divided into control and diabetic group. Furthermore each group was subdivided into 4 weeks, 8 weeks, 12 weeks and 16 weeks group. All experimental animal were put in the same environmental condition. Insulin-dependent diabetes mellitus was induced by intravenous injection of Streptozotocin65mgkg of body weight. Hair cell loss and their ultrastructural changes were observed with phase contrast light microscope and transmission electron microscope. ConclusionThe results of this study suggest that metabolic change of diabetes mellitus may affect the cochlear hair cells. Korean J Otolaryngol 408, 1997 KEY WORDSStreptozotocin Diabetes Rat Morphology Cochlea hair cell. 서 론 1162

2 재료및방법 1. 재료 2. 방법 1) 정상군 Korean J Otolaryngol 408, August ) 당뇨병모형군 3) 측두골적출및생체고정 1163

3 ) 위상차현미경관찰 5) 투과전자현미경적관찰 6) 통계적분석 결과 1. 체중의변화 2. 혈당치의변화 Table 1. Change of body weightgm in each group 4 weeks 8 wreeks 12 weeks 16 weeks Controln STZ n * * * * MeanStandard Deviation STZStreptozotocin-induced diabetic group *p0.05,compared with control group 1164

Korean J Otolaryngol 408, August 1997 Table 2. Change of blood glucose levelmg100ml in each group 4 weeks 8 wreeks 12 weeks 16 weeks Controln16 76.1 18.9 79.3 21 87.9 13 82.2 88 STZ n16 476.

4 Korean J Otolaryngol 408, August 1997 Table 2. Change of blood glucose levelmg100ml in each group 4 weeks 8 wreeks 12 weeks 16 weeks Controln STZ n * * * * MeanStandard Deviation STZStreptozotocin-induced diabetic group *p0.05,compared with control group Table 3. Hair cell loss% in different portions of the cochlea of control and STZ groups Outer hair cell Inner hair cell Hook 1st Turn 2nd Turn 3rd Turn 4 weeks Control STZ weeks Control STZ weeks Control STZ ** weeks Control STZ * ** MeanStandard Deviation STZStreptozotocin-induced diabetic group *p0.05, compared with the diabetic groups of the other weeks in the hook portion **p0.05, compared with the diabetic groups of the other weeks in the 1st turn 3. 와우유모세포의손실 1) 정상군과당뇨병모형군의비교 2) 당뇨병모형군간의비교 Fig. 1. Phase contrast micrograph of outer hair cellsoh and inner hair cellsih in the first turn of the cochlea at the control group of the 16th week. Three rows of outer hair cellsarrow and one row of inner hair cellsarrow head are well preserved1% Toluidine blue stain,

한이인지 제 4 0 권 제 8 호 1997 세포의 손실률은 12주군을 제외하고는 모두 기저회전 4. 와우유모세포의 형태학적 변화(전자현 미경적 소견) 에서 가장 크게 나타났으며 다음으로 중회전, 갈고리 부위, 첨단회전의 순서이었다.

이외에 모 (cilia)의 탈락과 같은 변화를 관찰할 수 있었고 세포 막의 부분적 파괴, 세포질(cytoplasm)의 공포화(vacuolization) 및 소기관(organell)의 종창 등 와우유 모세포의 변성을 관찰할 수 있었다(Fig. 3 Fig. 5). Fig. 2.

Fig. 4. Transmission electron micrograph of the first turn of the cochlea at the diabetic group of the 16th week.

Transmission electron micrograph of the outer hair cell in the first turn of the cochlea at the control group of the 16th week.

5 한이인지 제 4 0 권 제 8 호 1997 세포의 손실률은 12주군을 제외하고는 모두 기저회전 4. 와우유모세포의 형태학적 변화(전자현 미경적 소견) 에서 가장 크게 나타났으며 다음으로 중회전, 갈고리 부위, 첨단회전의 순서이었다. 투과전자현미경으로 관찰한 와우외유모세포의 주된 변화는 핵이 손실된 와우외유모세포의 관찰 및 지지 세포에 의한 와우외유모세포의 치환이었다. 이외에 모 (cilia)의 탈락과 같은 변화를 관찰할 수 있었고 세포 막의 부분적 파괴, 세포질(cytoplasm)의 공포화(vacuolization) 및 소기관(organell)의 종창 등 와우유 모세포의 변성을 관찰할 수 있었다(Fig. 3 Fig. 5). Fig. 2. Phase contrast micrographs of outer hair cell loss (arrow) in the first turn of cochlea at the diabetic group of the 16th week(1% Toluidine blue stain, 400). Fig. 4. Transmission electron micrograph of the first turn of the cochlea at the diabetic group of the 16th week. Note displacement of outer phalangeal cell(thin arrow) and irregular contours and cytoplasmic vacuolization of outer hair cells(thicker arrow)( 1,200). Fig. 3. Transmission electron micrograph of the outer hair cell in the first turn of the cochlea at the control group of the 16th week. Cuticular plate(c), stereocilia(h), mitochodria(m), nucleus(n)( 4,000). Fig. 5. Transmission electron micrograph of outer hair cells of the first turn of the cochlea at the diabetic group of the 16th week. Note irregular outlines (thicker arrow) of outer hair cells showing vesicular cytoplasm(asterisk) with swollen mitochondria(thin arrow)( 2,500). 1166

6 고찰 Korean J Otolaryngol 408, August

8 Korean J Otolaryngol 408, August 1997 요 약 References 1) Jordao AMD:Consideration sur un cas du dia- 1169

9 bete. Union Med Paris. 1961;11: ) Jorgensen MB:The inner ear in diabetes mellitus. Arch Otolaryngol Head Neck Surg. 1961;74: ) Axelsson A, Fagerberg SE:Auditory function in diabetes. Acta Otolaryngol(Stockh). 1968;66: ) Harner SG:Hearing and adult onset diabetes mellitus. Otolaryngol Head Neck Surg. 1981; 327: ) Won KH, Yeo SW, Kim CK, Suh BD:Clinical observation on hearing impairment in diabetes mellitus. Korean J Otolaryngol. 1984;27(4): ) Rakieten N, Rakieten ML, Nadkarni MV:Studies on the diabetogenic action of streptozotocin(nsc ). Cancer Chemother Rep. 1963;29: ) Pilsbury HC:Hypertension, hyperlipidemia, chronic noise exposure:is there synergism in cochlear pathology? Laryngoscope. 1986;96: ) Raynor ER, Carrasco VN, Prazma J, Pilsbury HC:An assessment of cochlear hair-cell loss in insulindependent diabetes mellitus diabetic and noise-exposed rat. Arch Otolaryngol Head Neck Surg. 1995;121: ) Wackym PA, Linthicum FH:Diabetes mellitus and hearing loss:clinical and histopathologic relationships. Am J of Otol. 1986;7: ) Booth JB:Diabetes Mellitus. Scott-Brown s Otolaryngology 5th ed. Butterworth Co Ltd London. 1987: ) Costa OA:Inner ear pathology in experinental diabetes. Laryngoscope. 1996;77: ) Makishima K, Tanaka K:Pathological changes of the inner ear and central auditory pathway in diabetics. Ann Otol Rhinol Laryngol. 1971;80: ) Friedman SA, Schulman RH, Weiss S:Hearing and diabetic neuropathy. Arch Intern Med. 1975; 135: ) Myers SF, Ross MD, Jokelainen P, Graham MD, Mcclatchey KD:Morphological evidence of vestibular pathology in long-term experimental diabetes mellitus. I. Microvascular change. Acta Otolaryngol(Stockh). 1987;104: ) Schlosser MJ, Kapeghian JC, Verlangier AJ: Selected physical and biochemical parameters in the strreptozotocin-treated guinea pig:insights into the diabetic guinea pig model. Life Sci. 1987;41: ) Rust KR, Prazma J, Triana RJ, Michaelis OE, Pillsbury HC:Inner ear damage secondary to diabetes mellitus. Arch Otolaryngol Head Neck Surg. 1992;118: ) Nakae S, Tachibana M:The cochlea of the spontaneously diabetic mouse. II. Electron microscopic observations of non-obese diabetic mice. Arch Otorhinolaryngol. 1986;243: ) Aamer AR, Bo A:Long-term diabetogenic effect of streptozotocin in rats. Pancreas. 1993;8(1): ) Gladney JH:Experimental diabetes and the inner ear. Ann Otol Rhinol Laryngol. 1978;87: ) Bohne BA:Location of small cochlear lesions by phase contrast microscopy prior to thin sectioning. Laryngoscope. 1972;82:

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