Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
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방광 발달과정에서 Nerve Growth Factor의 발현

Expression of Nerve Growth Factor during Urinary Bladder Development

  • 이경은 (한림대학교 의과대학 소아과학교실) ;
  • 홍창희 (한림대학교 의과대학 비뇨기과학교실) ;
  • 강희정 (한림대학교 의과대학 진단검사의학교실) ;
  • 김덕하 (한림대학교 의과대학 소아과학교실)
  • Lee, Kyoung Eun (Department of Pediatrics, College of Medicine, Hallym University) ;
  • Hong, Chang Hee (Department of Urology, College of Medicine, Hallym University) ;
  • Kang, Hee Jung (Department of Laboratory Medicine, College of Medicine, Hallym University) ;
  • Kim, Dug Ha (Department of Pediatrics, College of Medicine, Hallym University)
  • 투고 : 2004.09.17
  • 심사 : 2004.12.03
  • 발행 : 2005.04.15
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초록

목 적 : 방광의 발달과정은 척수배뇨반사에서 척수연수척수반사로의 전환을 특징으로 한다고 알려져 왔다. 향신경인자가 이러한 방광의 발달과정에 관여한다는 동물연구에도 불구하고 인간의 방광 발달과정에도 향신경인자가 역할을 하는지에 관한 연구는 없는 실정이다. 본 연구는 인간의 방광 발달과정에 향신경인자가 관여할 것이라는 가정 하에 방광 발달과정에서 소변의 nerve growth factor(NGF) 변화를 관찰하였다. 방 법 : 배뇨생식기의 선천적 이상을 동반하지 않고 배뇨이상, 요로감염의 증거가 없는 지원자 60명을 대상으로 하였다. 지원자는 출생 후 한달 미만의 신생아, 1년 미만의 유아, 1세, 2세, 3세, 4세의 소아로 분류하였고 각각 10명씩 소변을 채취하였다. 소변의 NGF의 정량은 ELISA 방법을 이용하였고 소아의 연령, 요자제 유무에 따른 NGF의 변화를 NGF/Cr, NGF/total protein 값으로 비교하였다. 결 과 : 연령별로 NGF/Cr은 신생아에서 증가하였다가 유아에 감소하고 1세, 2세에 증가하였다가 3세 때부터 감소하였다. 신생아에서 다른 군과 비교하였을 때 의미있는 증가가 관찰이 되었고(P<0.05) 다른 군에서는 의미있는 차이를 보이지는 않았다. NGF/total protein도 NGF/Cr과 비슷한 양상으로 관찰이 되었다. 자발적 배뇨조절이 가능한 소아는 1세에 2명, 2세에 8명, 3세와 4세에는 10명씩이었다. 1세 이상에서 요자제 유무에 따른 NGF/Cr을 비교하였을 때 요자제가 있는 소아에서 의미있게 감소하였다(P<0.05). 결 론 : 단절배뇨와 높은 방광압력을 특징으로 하는 요자제 이전에 NGF가 증가하였다가 요자제 이후에는 감소하는 것을 확인하였다. 이는 배뇨근-괄약근 협동장애로 인해 증가된 방광조직의 NGF가 역행성 축삭수송을 통해 중추신경계에서 척수반사를 척수연수척수반사로 성숙시키고 이것이 다시 배뇨근-괄약근 성숙을 통해 요자제를 형성하였다고 추정할 수 있다. 이는 인간의 방광 발달과정에도 향신경인자가 방광신경 성장과 배뇨반사의 재구성에 관여함을 시사한다고 생각한다.

Purpose : This study was performed to determine the developmental expression pattern of nerve growth factor(NGF) in the urine of healthy children. It was hypothesized that NGF may contribute to the development of the spinobulbospinal micturition reflex that represents the adult micturition pattern. Methods : Voided urine was collected in 60 healthy children during the first 5 years of life(0-1 month, n=10; 1 month-1 year, n=10; 2 years, n=10; 3 years, n=10; 4 years, n=10). The urinary NGF was analyzed by using an enzyme linked immunosorbent assay. Results were normalized based on creatinine or total protein in urine. Results : NGF was significantly greater among neonates compared to other age groups(P<0.05). NGF levels declined during 1 month to 1 year and increased by age 2 years. NGF levels at age 3 years were less than in neonates examined. When comparing the NGF levels according to continence in children over 1 year old, NGF levels were significantly lower in children with continence than in children with incontinence(P<0.05). Conclusion : These data suggest that NGF is involved in the achievement of continence and in mechanisms of bladder nerve growth and in the reorganization of bladder reflex pathway.

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참고문헌

  1. de Groat WC, Nadelhaft I, Miline RJ, Booth AM, Morgan C, Thor K. Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine. J Auton Nerv Syst 1981;3:135-60 https://doi.org/10.1016/0165-1838(81)90059-X
  2. Thor KB, Blais DP, de Groat WC. Behavioral analysis of the postnatal development of micturition in kittens. Brain Res Dev Brain Res 1989;46:137-44 https://doi.org/10.1016/0165-3806(89)90151-X
  3. Maggi CA, Santicioli P, Geppeti S, Frilli MG, Spillantini MG, Nediani C, et al. Biochemical, anatomical and functional correlates of postnatal development of the capsaicinsensitive innervation of the rat urinary bladder. Brain Res 1988;471:183-90
  4. Bregman BS. Development of serotonin immunoreactivity in the rat spinal cord and its plasticity after neonatal spinal cord lesions. Brain Res 1987;431:245-63
  5. Fitzgerald M. Development of pain mechanisms. Br Med Bull 1991;47:667-75
  6. Kruse MN, Tanowitz M, Chent C, de Groat WC. Postnatal development of the sensory innervation of the urinary bladder in the rat. Soc Neurosci 1990;16:1064
  7. Marti E, Gibson SJ, Polak JM, Facer P, Springall DR, Van Aswegen G, et al. Ontogeny of peptide and amine containing neurones in motor, sensory, and autonomic regions of rat and human spinal cord, dorsal root ganglia and rat skin. J Comp Neurol 1987;266:332-59 https://doi.org/10.1002/cne.902660304
  8. Vizzard MA, Erdman SL, Forstermann U, de Groat WC. Ontogeny of nitric oxide synthase in the lumbosacral spinal cord of the neonatal rat. Brain Res Dev Brain Res 1994; 81:201-17 https://doi.org/10.1016/0165-3806(94)90307-7
  9. Kawakami T, Wakabayashi Y, Aimi Y, Isono T, Okada Y. Developmental expression of glial cell-line derived neurotrophic factor, neurturin, and their receptor mRNA in the rat urinary bladder. Neurourol Urodyn 2003;22:83-8 https://doi.org/10.1002/nau.10074
  10. Lewin GR, Barde YA. Physiology of the neurotrophins. Annu Rev Neurosci 1996;19:289-317 https://doi.org/10.1146/annurev.ne.19.030196.001445
  11. Vizzard MA, Wu KH, Jewett IT. Developmental expression of urinary bladder neurotrophic factor mRNA and protein in the neonatal rat. Brain Res Dev Brain Res 2000;119:217-24 https://doi.org/10.1016/S0165-3806(99)00174-1
  12. Dines KC, Powell HC. Mast cell interactions with the nervous system : relationship to mechanisms of disease. J Neuropathol Exp Neurol 1997;56:627-40
  13. Oddiah D, Anand P, McMahon SB, Rattray M. Rapid increase of NGF, BDNF and NT-3 mRNAs in inflamed bladder. Neuroreport 1998;9:1455-8 https://doi.org/10.1097/00001756-199805110-00038
  14. Vizzard MA. Changes in urinary bladder neurotrophic factor mRNA and NGF protein following urinary bladder dysfunction. Exp Neurol 2000;161:273-84 https://doi.org/10.1006/exnr.1999.7254
  15. Steers WD, Kolbeck S, Creedon D, Tuttle JB. Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. J Clin Invest 1991;88:1709-15 https://doi.org/10.1172/JCI115488
  16. Dupont MC, Persson K, Spitsbergen J, Tuttle JB, Steers WD. The neuronal response to bladder outlet obstruction, a role for NGF. Adv Exp Med Biol 1995;385:41-54
  17. Wakabayashi Y, Kawakami T, Aimi Y, Okada Y. Development of growth-associated protein-43 and neurotrophin receptor immunoreactivities in the rat urinary bladder. Anat Embryol 2002;205:255-61 https://doi.org/10.1007/s00429-002-0246-9
  18. Kawakami T, Wakabayashi Y, Isono T, Aimi Y, Okada Y. Expression of neurotrophin messenger RNAs during rat urinary bladder development. Neurosci Lett 2002;329:77-80 https://doi.org/10.1016/S0304-3940(02)00598-0
  19. Jansson UB, Hanson M, Hanson E, Hellstrom AL, Sillen U. Voiding pattern in healthy children 0 to 3 years old : a longitudinal study. J Urol 2000;164:2050-4 https://doi.org/10.1016/S0022-5347(05)66963-7
  20. Lee KW, Kim JH, Kim YJ, Lee CH, Jeon YS, Lee NK. Voiding patterns in healthy korean children below 3 years old. Korean J Urol 2004;45:209-14
  21. Yeung CK, Godley ML, Dhillon HK, Duffy PG, Ransley PG. Urodynamic patterns in infants with normal lower urinary tracts or primary vesico-ureteric reflux. Br J Urol 1998;81:461-7 https://doi.org/10.1046/j.1464-410x.1998.00567.x
  22. Bachelard M, Sillen U, Hansson S, Hermansson G, Jodal U, Jacobsson B. Urodynamic pattern in asymptomatic infants : siblings of children with vesicoureteral reflux. J Urol 1999;162;1733-8 https://doi.org/10.1016/S0022-5347(05)68226-2
  23. de Groat WC. Plasticity of bladder reflex pathways during postnatal development. Physiol Behav 2002;77:689-92 https://doi.org/10.1016/S0031-9384(02)00919-8
  24. Lommatzsch M, Braun A, Mannsfeldt A, Botchkarev VA, Botchkareva NV, Paus R, et al. Abundant production of brain-derived neurotrophic factor by adult visceral epithelia : implication for paracrine and target-derived neurotrophic functions. Am J Pathol 1999;155:1183-93 https://doi.org/10.1016/S0002-9440(10)65221-2
  25. Kim JC, Seo SI, Park YH, Hwang TK. Changes in detrusor and urinary growth factors according to detrusor function after partial bladder obstruction in the rat. Urology 2001;57:371-5 https://doi.org/10.1016/S0090-4295(00)00886-4
  26. Okragly AJ, Niles AL, Saban R, Schmidt D, Hoffman RL, Warner TF, et al. Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients. J Urol 1999;161:438-41 https://doi.org/10.1016/S0022-5347(01)61915-3