CAJ | 학술논문

Huntington病(HD)是一种常染色体显性遗传性神经退行性疾病,主要组织病理学特征是纹状体运动神经元进行性死亡,目前尚无有效治疗方法,本实验探讨了nortriptyline(去甲替林)的潜在疗效.采用N548mu[1955-128]huntingtin ST14A细胞系进行体外培养,观察不同浓度nortriptyline对细胞存活的影响.选用R6/2转基因鼠,从第5周开始每天腹腔注射nortriptyline,直至21周,对照组腹腔注射与nortriptyline组等剂量的生理盐水.结果发现,nortriptyline对移入不同温度环境的ST14A细胞具有保护作用.nortriptyline可推迟R6/2转基因鼠的发病,由102 d推迟到127 d,与对照组比较具有显著性差异.nortriptyline对R6/2转基因鼠死亡率的影响,与对照组比较无显著性差异.作为检测nortriptyline毒性的指标,nortriptyline对R6/2转基因鼠体重的影响,与对照组比较无显著性差异.结果表明,nortriptyline可推迟Huntington转基因鼠的发病,是目前毒性低、能够延长Huntington转基因鼠存活的有效药物.
Huntington병(HD)시일충상염색체현성유전성신경퇴행성질병,주요조직병이학특정시문상체운동신경원진행성사망,목전상무유효치료방법,본실험탐토료nortriptyline(거갑체림)적잠재료효.채용N548mu[1955-128]huntingtin ST14A세포계진행체외배양,관찰불동농도nortriptyline대세포존활적영향.선용R6/2전기인서,종제5주개시매천복강주사nortriptyline,직지21주,대조조복강주사여nortriptyline조등제량적생리염수.결과발현,nortriptyline대이입불동온도배경적ST14A세포구유보호작용.nortriptyline가추지R6/2전기인서적발병,유102 d추지도127 d,여대조조비교구유현저성차이.nortriptyline대R6/2전기인서사망솔적영향,여대조조비교무현저성차이.작위검측nortriptyline독성적지표,nortriptyline대R6/2전기인서체중적영향,여대조조비교무현저성차이.결과표명,nortriptyline가추지Huntington전기인서적발병,시목전독성저、능구연장Huntington전기인서존활적유효약물.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease. A cardinal histopathologic feature of HD is the progressive loss of striatal medium spiny neurons. As there is no effective treatment for this fatal disease so far, we explore the therapeutic potential of nortriptyline to identify drugs that might be effective treatments for HD. N548mu [ 1955-128] huntingtin stable ST14A cell line was cultured and incubated in the presence or absence of serial concentrations of nortriptyline. Then R6/2 transgenic HD mice were treated with nortriptyline from five to twenty-one weeks of age. Nortriptyline protected striatal cells expressing mutant huntingtin when shifted to a nonpermissive temperature. Nortriptyline delay the disease onset to 127 d in R6/2 mice as compared with 102 d in saline-treated controls, but nortriptyline did not significantly delay mortality. As a gross marker of lack of systemic toxicity, there was no significant difference in the weight of the treated and control R6/2 mice. The results demonstrate that clinically reasonable doses of one of the identified drugs, nortriptyline, delays disease onset in a mouse model of the disease more than any previously identified compound. The most desirable features of a drug for HD are minimal toxicity and the ability to extend symptom-free living. Nortriptyline appears to be one such good candidate.