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第42卷第11期       丁文筱,张     蔷,丁 宁,等. 球形脂联素对间歇低氧所致H9C2细胞损伤的保护作用及机制[J].
                 2022年11月                  南京医科大学学报(自然科学版),2022,42(11):1523-1529,1538                   ·1529 ·


                等 [18] 发现gAPN可通过上调自噬减轻对乙酰氨基酚                     [5] URBINA⁃VARELA R,CASTILLO N,VIDELA L A,et al.
                所致肝损伤。Zhu 等       [19] 发现 gAPN 可减轻心肌缺血                 Impact of mitophagy and mitochondrial unfolded protein
                再灌注损伤,提示 gAPN 具有心肌保护作用。前期                              response as new adaptive mechanisms underlying old pa⁃
                研究发现gAPN可上调线粒体自噬减轻IH所致大鼠                               thologies:sarcopenia and non⁃alcoholic fatty liver disease
                                                                      [J]. Int J Mol Sci,2020,21(20):7704
                颏舌肌损伤      [20] 。与前期研究一致,本研究发现
                                                                 [6] REN Y H,LI Y,YAN J,et al. Adiponectin modulates oxi⁃
                gAPN 可减轻 IH 所致 H9C2 心肌细胞线粒体损伤及
                                                                       dative stress⁃induced mitophagy and protects C2C12 myo⁃
                细胞凋亡。同时发现与IH相比,gAPN可进一步上调
                                                                       blasts against apoptosis[J]. Sci Rep,2017,7(1):3209
                Parkin介导的线粒体自噬。然而,当Parkin siRNA抑                 [7] OTVOS L. Potential adiponectin receptor response modifier
                制 Parkin 表达后,gAPN 诱导的线粒体自噬被抑制,                         therapeutics[J]. Front Endocrinol,2019,10:539
                线粒体损伤及细胞凋亡明显增加,提示 gAPN 通过                        [8] AL MUTAIRI S,MOJIMINIYI O A,AL ALAWI A,et al.
                上调Parkin介导的内质网自噬减轻IH所致H9C2心                            Study of leptin and adiponectin as disease markers in sub⁃
                                        [6]
                肌细胞损伤。然而,Ren 等 发现全长脂联素通过                               jects with obstructive sleep apnea[J]. Dis Markers,2014,
                抑制 Pink1/Parkin 介导的线粒体自噬减轻过氧化氢                         2014:706314
                                                                 [9] DING W X,ZHANG X F,HUANG H P,et al. Adiponec⁃
                所致C2C12 细胞损伤,这与本研究不同。多项研究
                                                                       tin protects rat myocardium against chronic intermittent
                发现全长脂联素和 gAPN 具有不同甚至相反的作
                                                                       hypoxia⁃induced injury via inhibition of endoplasmic re⁃
                用。Bang 等  [21] 发现全长脂联素具有抗黑色素形成
                                                                       ticulum stress[J]. PLoS One,2014,9(4):e94545
                作用,而 Kim 等    [22] 发现 gAPN 具有促进黑色素形成             [10] ZHANG Q,ZHANG X L,DING N,et al. Globular adipo⁃
                作用。Burkus 等   [23] 发现全长脂联素而非gAPN 可促                    nectin alleviates chronic intermittent hypoxia ⁃ induced
                进小鼠囊胚细胞葡萄糖摄取。因此推测不同形态                                  H9C2 cardiomyocytes apoptosis via ER⁃phagy induction
                的脂联素及不同的实验条件可能是本研究与 Ren                               [J]. Cell Cycle Georget Tex,2020,19(22):3140-3153
                  [6]                                            [11] TIETJENS J R ,CLAMAN D ,KEZIRIAN E J ,et al.
                等 研究不同的主要原因。本研究提示上调Parkin
                介导的线粒体自噬是 gAPN 减轻 IH 所致 H9C2 心肌                        Obstructive sleep apnea in cardiovascular disease:a re⁃
                细胞损伤的机制。                                               view of the literature and proposed multidisciplinary clini⁃
                                                                       cal management strategy[J]. J Am Heart Assoc,2019,8
                    综上所述,本研究发现 Parkin 介导的线粒体自
                                                                      (1):e010440
                噬 在 IH 诱 导 的 H9C2 心 肌 损 伤 中 起 保 护 作 用。
                                                                 [12] ZHANG X,RUI L,LV B,et al. Adiponectin relieves hu⁃
                gAPN通过上调Parkin介导的线粒体自噬减轻IH所
                                                                       man adult cardiac myocytes injury induced by intermit⁃
                致H9C2心肌细胞线粒体损伤及细胞凋亡。本研究                                tent hypoxia[J]. Med Sci Monit,2019,25:786-793
                有一定的局限性,IH细胞模型不能完全模拟OSAHS                        [13] IORIO R,CELENZA G,PETRICCA S. Mitophagy:molec⁃
                在体模型。因此未来将进行体内实验,进一步研究                                 ular mechanisms,new concepts on parkin activation and
                线粒体自噬的作用及相关机制,探索 gAPN 减轻 IH                            the emerging role of AMPK/ULK1 axis[J]. Cells,2022,
                所致心肌损伤的机制,为 gAPN 治疗 OSAHS 提供一                          11(1):30
                                                                 [14] 刁佳宇,赵宏谋,宁玉洁,等. 迷迭香酸激活Parkin介导
                定的理论基础。
                                                                       的线粒体自噬并抑制高糖诱导的心肌细胞肥大[J]. 南
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                    2019,200(4):493-506                                                         (下转第1538页)
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