Page 60 - 《中国药房》2026年7期
P. 60

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
   55   56   57   58   59   60   61   62   63   64   65