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表2 各组大鼠海马组织中 GRB2、CRLS1 蛋白表达水 nation signal for mitophagy in neuronal cells[J]. Nat Cell
平及ERK蛋白的磷酸化水平比较(x±s,n=3) Biol,2013,15(10):1197.
CRLS1 [ 6 ] LEE R G,BALASUBRAMANIAM S,STENTENBACH
组别 GRB2/GAPDH p-ERK/ERK
CRLS1/GAPDH 荧光强度 M,et al. Deleterious variants in CRLS1 lead to cardiolipin
SHAM组 1.06±0.03 0.58±0.02 0.84±0.05 0.026±0.015 deficiency and cause an autosomal recessive multi-system
MOD组 0.67±0.04 a 0.22±0.02 a 0.49±0.03 a 0.001±0.000 a mitochondrial disease[J]. Hum Mol Genet,2022,31(21):
YFXF-L组 0.79±0.04 b 0.36±0.01 b 0.64±0.03 b 0.007±0.001 b
YFXF-H组 0.89±0.06 b 0.51±0.02 b 0.69±0.02 b 0.010±0.006 b 3597-3612.
DH组 0.96±0.04 b 0.50±0.03 b 0.71±0.02 b 0.015±0.002 b [ 7 ] NIZZARI M,VENEZIA V,REPETTO E,et al. Amyloid
a:与SHAM组比较,P<0.05;b:与MOD组比较,P<0.05。 precursor protein and Presenilin 1 interact with the adap‐
表3 各组大鼠海马组织中GRB2、CRLS1、TAZ、PLSCR3、 tor GRB2 and modulate ERK 1,2 signaling[J]. J Biol
ND1 mRNA相对表达量比较(x±s,n=3) Chem,2007,282(18):13833-13844.
组别 GRB2 CRLS1 TAZ PLSCR3 ND1 [ 8 ] LUO H C,YI T Z,HUANG F G,et al. Role of long non‐
SHAM组 1.00±0.06 1.00±0.09 1.00±0.08 1.00±0.10 1.00±0.20 coding RNA MEG3/miR-378/GRB2 axis in neuronal
MOD组 0.22±0.02 a 0.21±0.02 a 0.48±0.04 a 0.28±0.08 a 0.15±0.01 a autophagy and neurological functional impairment in ischemic
YFXF-L组 0.46±0.05 b 0.52±0.06 b 0.67±0.05 b 0.67±0.02 b 0.52±0.03 b stroke[J]. J Biol Chem,2020,295(41):14125-14139.
YFXF-H组 0.60±0.04 b 0.72±0.05 b 0.81±0.03 b 0.87±0.03 b 0.67±0.17 b [ 9 ] 陈炜,朱小敏,胡跃强,等 . 益肺宣肺降浊方通过 EGFR
DH组 0.67±0.11 b 0.79±0.10 b 0.85±0.02 b 0.91±0.04 b 0.70±0.08 b
调节 PI3K/Akt-MAPK/Erk 通路改善血管性痴呆大鼠的
a:与SHAM组比较,P<0.05;b:与MOD组比较,P<0.05。
记忆[J]. 中华中医药学刊,2023,41(8):46-50.
ERK 在磷酸化后可转位入核,进而升高 CRLS1 的转录
[10] 黄晓丹. 益肺宣肺降浊方联合多奈哌齐治疗痰浊阻窍型
[18]
水平 。本研究发现,YFXF 干预后可显著提高 VAD 模
血管性痴呆的临床研究[D]. 南宁:广西中医药大学,2019.
型大鼠海马组织中 GRB2、CRLS1 的蛋白表达水平及
[11] 卓桂锋,陈炜,张金枝,等. 益肺宣肺降浊方抗血管性痴
ERK 蛋白的磷酸化水平,提升海马组织中 ATP 含量和 呆的作用机制研究[J]. 中国药房,2024,35(18):2207-2212.
GRB2、ND1 mRNA表达水平。其中,ATP含量的恢复直 [12] SUSTARSIC E G,MA T,LYNES M D,et al. Cardiolipin
接反映了线粒体能量合成功能的改善,而 ND1 mRNA synthesis in brown and beige fat mitochondria is essential
表达上调则表明线粒体生物合成得到促进。这一结果 for systemic energy homeostasis[J]. Cell Metab,2018,28
提示,YFXF 治疗 VAD 的作用机制可能与激活 GRB2/ (1):159-174.e11.
ERK/CRLS1通路、维护心磷脂稳态与线粒体功能有关。 [13] MATSUMURA A,HIGUCHI J,WATANABE Y,et al.
综上,YFXF可能通过激活GRB2/ERK/CRLS1通路 Inactivation of cardiolipin synthase triggers changes in
维护心磷脂稳态,改善线粒体能量代谢,从而改善 VAD mitochondrial morphology[J]. FEBS Lett,2018,592(2):
209-218.
模型大鼠海马神经元损伤。本研究为中药复方调控线
[14] LEE R G,GAO J J,SIIRA S J,et al. Cardiolipin is
粒体代谢防治VAD提供了新依据,但实验方面缺乏使用
required for membrane docking of mitochondrial ribo‐
特异性的激动剂或抑制剂对通路各节点进行功能增益
somes and protein synthesis[J]. J Cell Sci,2020,133(14):
或阻断,有待后续进一步的深入研究。
jcs240374.
参考文献 [15] NGUYEN H M,MEJIA E M,CHANG W G,et al. Reduc‐
[ 1 ] HE Y Y,HE T T,LI H P,et al. Deciphering mitochondrial tion in cardiolipin decreases mitochondrial spare respira‐
dysfunction:pathophysiological mechanisms in vascular tory capacity and increases glucose transport into and
cognitive impairment[J]. Biomed Pharmacother,2024, across human brain cerebral microvascular endothelial
174:116428. cells[J]. J Neurochem,2016,139(1):68-80.
[ 2 ] MORGAN A E,MC AULEY M T. Vascular dementia: [16] PEDRO R P,DIAS R V R,MARTINS I B S,et al. Con‐
from pathobiology to emerging perspectives[J]. Ageing formational flexibility of GRB2 as a key factor in the sta‐
Res Rev,2024,96:102278. bility and regulation of its interaction with SOS1[J]. ACS
[ 3 ] QI L F R,LIU S,FANG Q Y,et al. Ginsenoside Rg3 Omega,2025,10(27):29119-29130.
restores mitochondrial cardiolipin homeostasis via GRB2 [17] QU Y Y,CHEN Q,LAI X P,et al. SUMOylation of Grb2
to prevent Parkinson’s disease[J]. Adv Sci,2024,11(39): enhances the ERK activity by increasing its binding with
2403058. Sos1[J]. Mol Cancer,2014,13:95.
[ 4 ] DE GODOY J M P,DE GODOY M R P,CIPULO J P, [18] LIU J L,DALAMAGA M. Targeting cardiolipin metabo‐
et al. Vascular dementia and anticardiolipin antibodies[J]. lism for Parkinson’s disease therapy[J]. Metabol Open,
Med Sci Monit,2005,11(9):CR430-CR433. 2024,24:100327.
[ 5 ] CHU C T,JI J,DAGDA R K,et al.Cardiolipin externaliza‐ (收稿日期:2025-12-23 修回日期:2026-03-09)
tion to the outer mitochondrial membrane acts as an elimi‐ (编辑:林 静)
· 882 · China Pharmacy 2026 Vol. 37 No. 7 中国药房 2026年第37卷第7期

