CAJ | 학술논문

核苷类似物(NRTIs)通过内源性核苷酸磷酸化途径活化,继而竞争性抑制逆转录酶,在抗HIV方面取得了显著疗效.长期使用NRTIs可抑制DNA聚合酶γ,损害线粒体DNA合成与修复,从而影响细胞氧化呼吸并导致组织损伤.有关NRTIs的神经毒性主要集中在对外周神经损伤的研究.由于大脑线粒体的高含量,血脑屏障对于NRTIs的可通透性以及HIV相关认知障碍的高患病率使得对于NRTIs中枢神经系统毒性的研究显得尤为重要和紧迫.此文就这方面研究的最新进展作了综述.
핵감유사물(NRTIs)통과내원성핵감산린산화도경활화,계이경쟁성억제역전록매,재항HIV방면취득료현저료효.장기사용NRTIs가억제DNA취합매γ,손해선립체DNA합성여수복,종이영향세포양화호흡병도치조직손상.유관NRTIs적신경독성주요집중재대외주신경손상적연구.유우대뇌선립체적고함량,혈뇌병장대우NRTIs적가통투성이급HIV상관인지장애적고환병솔사득대우NRTIs중추신경계통독성적연구현득우위중요화긴박.차문취저방면연구적최신진전작료종술.
Nucleoside analogue reverse transcriptase inhibitors (NRTIs) represent key compoents of the antiretroviral combinations used to control HIV infection via endogenous nucleotide phosphorylation pathway. Many of the important and treatment limiting side-effects of nucleoside analogues have been suggested to be related to the impacts of these agents on mitochondrial DNA polymerase gamma. Depletion of mitochondrial DNA or impacts of these agents on mitochondrial enzymes during chronic nucleoside analogue therapy may lead to cellular respiratory dysfunction and tissue toxicities. In particular, peripheral neuropathy represents a rare but clinical manifestation of mitochondrial dysfunction in spite of HIV direct infringement cannot be ruled out. However, characteristics and mechanims of central neuropathy by nucleoside analogue still remain unknown. Management of potentially mitochondrial toxicity during nucleoside analogue therapy remains a challenge. Therefore, interruption of nucleoside analogue therapy and finding out mechanism of nucleoside analogue inducing central neuropathy remain important.