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[22]
应 。有文献表明,YAP蛋白的磷酸化能有效改善肝纤 研究新进展[J]. 河北医药,2020,42(20):3148-3153.
维化,且 AMPK 可以促进 YAP 蛋白的磷酸化,从而阻滞 LI X Z,DONG J X,XU X D. New research progress on
后者介导的信号转导 [8―9] 。为了探究 Sin 是否能够通过 the anti-inflammatory analgesic effects of sinomenine and
激活 AMPK 信号通路来促进 YAP 的磷酸化,从而抑制 its action mechanism[J]. Hebei Med J,2020,42(20):
3148-3153.
YAP 信号通路,进而抑制 NASH 中的炎症反应,本研究
[11] LI R Z,GUAN X X,WANG X R,et al. Sinomenine hy‐
利用 Western blot 技术进行检测。结果显示,与 SCD 组
小鼠和对照组 HepG2 细胞比较,HFD 组小鼠肝组织和 drochloride bidirectionally inhibits progression of tumor
and autoimmune diseases by regulating AMPK pathway
OA 组 HepG2 细胞中 YAP 蛋白的磷酸化水平均显著降
[J]. Phytomedicine,2023,114:154751.
低,而不同剂量/浓度的 Sin 均能增加小鼠肝组织和 [12] LAN T,YU Y,ZHANG J,et al. Cordycepin ameliorates
HepG2细胞中YAP蛋白的磷酸化水平。上述结果表明, nonalcoholic steatohepatitis by activation of the AMP-
AMPK/YAP信号通路可能是Sin缓解NASH的重要靶点 activated protein kinase signaling pathway[J]. Hepato-
之一。 logy,2021,74(2):686-703.
综上所述,Sin 可抑制 NASH 小鼠的炎症反应和肝 [13] FAN H,TU T T,ZHANG X,et al. Sinomenine attenuates
脏脂质蓄积,减轻肝纤维化,上述改善作用可能与激活 alcohol-induced acute liver injury via inhibiting oxidative
AMPK信号通路、促进YAP蛋白磷酸化相关。虽然本研 stress,inflammation and apoptosis in mice[J]. Food Chem
究提出了 Sin 基于 AMPK/YAP 信号通路改善 NASH 的 Toxicol,2022,159:112759.
潜在机制,但 NASH 发病机制复杂,是否涉及其他信号 [14] YUAN M L,ZHAO B,JIA H P,et al. Sinomenine ame-
通路及通路间的相互作用仍有待后续进一步探讨。 liorates cardiac hypertrophy by activating Nrf2/ARE signa-
参考文献 ling pathway[J]. Bioengineered,2021,12(2):12778-
[ 1 ] FRASER D A,WANG X Y,LUND J,et al. A structurally 12788.
[15] SHEKA A C,ADEYI O,THOMPSON J,et al. Nonalco‐
engineered fatty acid,icosabutate,suppresses liver inflam‐ holic steatohepatitis:a review[J]. JAMA,2020,323(12):
mation and fibrosis in NASH[J]. J Hepatol,2022,76(4): 1175-1183.
800-811. [16] GU H P,LI J R,NI Y H. Sinomenine improves renal fibro‐
[ 2 ] SCHUSTER S,CABRERA D,ARRESE M,et al. Trig-
gering and resolution of inflammation in NASH[J]. Nat sis by regulating mesenchymal stem cell-derived exo‐
somes and affecting autophagy levels[J]. Environ Toxicol,
Rev Gastroenterol Hepatol,2018,15(6):349-364. 2023,38(10):2524-2537.
[ 3 ] HARRISON S A,ALLEN A M,DUBOURG J,et al. Chal‐ [17] LUO X J,LI H G,MA L Q,et al. Expression of STING is
lenges and opportunities in NASH drug development[J]. increased in liver tissues from patients with NAFLD and
Nat Med,2023,29(3):562-573.
[ 4 ] MIREA A M,TACK C J,CHAVAKIS T,et al. IL-1 family promotes macrophage-mediated hepatic inflammation and
fibrosis in mice[J]. Gastroenterology,2018,155(6):1971-
cytokine pathways underlying NAFLD:towards new treat‐ 1984.e4.
ment strategies[J]. Trends Mol Med,2018,24(5):458-471. [18]
[ 5 ] CHEN X,LI X,ZHANG W Y,et al. Activation of AMPK AJMERA V,LOOMBA R. Imaging biomarkers of NAFLD,
NASH,and fibrosis[J]. Mol Metab,2021,50:101167.
inhibits inflammatory response during hypoxia and reoxy‐
genation through modulating JNK-mediated NF-κB path‐ [19] ZHAO P,SUN X L,CHAGGAN C,et al. An AMPK-
caspase-6 axis controls liver damage in nonalcoholic steato-
way[J]. Metabolism,2018,83:256-270. hepatitis[J]. Science,2020,367(6478):652-660.
[ 6 ] FANG C Q,PAN J H,QU N,et al. The AMPK pathway in [20] KANG L J,YI J J,LAU C W,et al. AMPK-dependent
fatty liver disease[J]. Front Physiol,2022,13:970292. YAP inhibition mediates the protective effect of metfor‐
[ 7 ] SONG K,KWON H,HAN C,et al. Yes-associated pro‐
tein in Kupffer cells enhances the production of proinflam‐ min against obesity-associated endothelial dysfunction
and inflammation[J]. Antioxidants,2023,12(9):1681.
matory cytokines and promotes the development of nonal‐ [21] PERUMAL N,PERUMAL M,HALAGOWDER D,et al.
coholic steatohepatitis[J]. Hepatology,2020,72(1): Morin attenuates diethylnitrosamine-induced rat liver fi‐
72-87. brosis and hepatic stellate cell activation by co-ordinated
[ 8 ] TONG G Z,CHEN X X,LEE J,et al. Fibroblast growth
factor 18 attenuates liver fibrosis and HSCs activation via regulation of Hippo/YAP and TGF- β1/Smad signaling[J].
Biochimie,2017,140:10-19.
the SMO-LATS1-YAP pathway[J]. Pharmacol Res,2022, [22] MELI V S,ATCHA H,VEERASUBRAMANIAN P K,et
178:106139. al. YAP-mediated mechanotransduction tunes the macro‐
[ 9 ] LUO L,GUO J M,LI Y,et al. Klotho promotes AMPK
phage inflammatory response[J]. Sci Adv,2020,6(49):
activity and maintains renal vascular integrity by regula-
eabb8471.
ting the YAP signaling pathway[J]. Int J Med Sci,2023,20
(收稿日期:2023-12-29 修回日期:2024-05-09)
(2):194-205.
(编辑:张元媛)
[10] 李修政,董家潇,许晓东. 青藤碱抗炎镇痛作用及机制的
中国药房 2024年第35卷第14期 China Pharmacy 2024 Vol. 35 No. 14 · 1707 ·