摘要
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.
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.
出处
《国际流行病学传染病学杂志》
CAS
2010年第6期395-398,共4页
International Journal of Epidemiology and Infectious Disease
基金
国家自然科学基金重大国际合作项目(30910103915)
国家自然科学基金(30770742、30870853)