白藜芦醇通过调控TLR4及其甲基化水平缓解同型半胱氨酸诱导的小鼠胰岛β细胞氧化损伤

doi:10.3969/j.issn.1006-5725.2026.13.019

Abstract

Abstract:

Objective This study aims to explore the mechanism through which resveratrol （Res） mitigates homocysteine （Hcy）-induced oxidative damage in mouse pancreatic β-cells by regulating the expression and methylation level of the Toll-like receptor 4 （TLR4） gene. Methods The effects of different concentrations of homocysteine and resveratrol on the viability of mouse pancreatic β-cells were evaluated using the CCK-8 assay. In each group， the levels of malondialdehyde （MDA）， the activity of glutathione peroxidase （GSH-Px）， and the levels of insulin were measured using an MDA kit， a GSH-Px activity kit， and enzyme-linked immunosorbent assay （ELISA）， respectively. The oxidative stress status was assessed through fluorescence staining. The protein and mRNA expression levels of TLR4 in the control group， the Hcy group， and the homocysteine + resveratrol （Hcy + Res） co-treatment group were detected via Western blot and qRT-PCR. The DNA methylation level of TLR4 was determined using nested methylation-specific PCR， and the protein expression of DNMT1 （DNA methyltransferase 1） was measured by Western blot. Small interfering RNA fragments targeting DNMT1 were constructed and transfected into pancreatic β-cells. Subsequently， the TLR4 protein expression was detected by Western blot. The MDA levels， GSH-Px activity， and insulin levels in the DNMT1 knockdown groups were measured using the aforementioned kits. Likewise， small interfering RNA fragments targeting TLR4 were constructed and transfected into pancreatic β-cells， and then the MDA levels， GSH-Px activity， and insulin levels were measured. Results Cell viability decreased after treatment with 100 μmol/L Hcy. In contrast， intervention with 10 μmol/L Res effectively mitigated the Hcy-induced damage to pancreatic β-cells. Results from the MDA assay and fluorescence staining indicated that， when compared with the Control group， the Hcy group had elevated MDA and reactive oxygen species （ROS） levels （P 0.05）， while these levels declined in the Hcy+Res group （P 0.05）. Findings from the GSH-Px activity assay and ELISA demonstrated that， relative to the Control group， the Hcy group had reduced GSH-Px activity and insulin levels （P 0.05）， whereas the Hcy + Res group showed increased levels （P 0.05）. Western blot and qRT-PCR results showed that the expression levels of TLR4 protein and mRNA were significantly higher in the Hcy group than in the Control group （P 0.05）， while they were significantly lower in the Hcy + Res group （P 0.05）. Conversely， results from nested methylation-specific PCR showed that the TLR4 DNA methylation levels displayed an opposite trend. The expression of DNMT1 protein was lower in the Hcy group （P 0.05） and higher in the Hcy + Res group （P 0.05） compared with the Control group. The expression of TLR4 protein was significantly higher in the Hcy + si-DNMT1 group than in the Hcy + si-NC group （P 0.05）， and it was further increased in the Hcy + Res + si-DNMT1 group compared with the Hcy + Res group （P 0.05）. Compared with the Hcy + si-NC group， the MDA levels were significantly elevated in the Hcy + si-DNMT1 group （P 0.05）. Moreover， when compared with the Hcy + Res group， the MDA levels were further increased in the Hcy + Res + si-DNMT1 group （P 0.05）. The changes in GSH-Px activity and insulin levels were opposite to those of MDA. Further knockdown of TLR4 led to a decrease in MDA levels （P 0.05）， and there was an even greater reduction after Res intervention （P 0.05）. Conversely， GSH-Px activity and insulin levels increased （P 0.05）， and there was a further elevation after Res intervention （P 0.05）. Conclusion Resveratrol alleviates the oxidative damage in pancreatic β-cells induced by homocysteine， a process that is associated with alterations in TLR4 expression and its methylation level.

Key words: resveratrol, toll-like receptor 4, islet cells, homocysteine, methylation, oxidative damage

CLC Number:

R285.5

Minghua HAI,Jia MA,Xinru LI,Jiarong LUO,Rui SUN,Yuwei AN,Ben MA,Ruolin YAN,Chen WANG,Yuankui CHU,Xin YU,Shengchao MA. Resveratrol alleviates homocysteine-induced oxidative damage in mouse pancreatic β-cells by regulating toll-like receptor 4 and its methylation level[J]. The Journal of Practical Medicine, 2026, 42(13): 2428-2437.

Figures/Tables 16

Tab.1

Tab.2

Tab.3

Tab.4

Fig.1

Fig.2

Tab.5

Fig.3

Tab.6

Fig.4

Fig.5

Fig.6

Tab.7

Fig.7

Tab.8

Tab.9

References 35

[1]	INAISHI J， SAISHO Y. Beta-cell mass in obesity and type 2 diabetes， and its relation to pancreas fat： A mini-review［J］. Nutrients， 2020， 12（12）： 3846. doi：10.3390/nu12123846 . doi: 10.3390/nu12123846
[2]	李利函，王善龙，宋影. 血清Hcy、25-OH^-D3、SF水平与2型糖尿病患者胰岛素抵抗的关系［J］. 黑龙江医药科学， 2026， 49（2）： 76-78. doi：10.3969/j.issn.1008-0104.2026.02.024 . doi: 10.3969/j.issn.1008-0104.2026.02.024
[3]	马凌桔，汪乐新，迟宏扬，等.METTL3在同型半胱氨酸诱导小鼠胰岛β细胞自噬中的作用［J］.中国组织工程研究，2024，28（26）：4221-4225.doi： 10.12307/2024.423 doi: 10.12307/2024.423
[4]	YU X， JIA Y， REN F. Multidimensional biological activities of resveratrol and its prospects and challenges in the health field［J］. Front Nutr， 2024， 11： 1408651. doi：10.3389/fnut.2024. 1408651 . doi: 10.3389/fnut.2024. 1408651
[5]	GONG W， LI J， CHEN W， et al. Resveratrol inhibits lipopolysaccharide-induced extracellular matrix accumulation and inflammation in rat glomerular mesangial cells by SphK1/S1P2/NF-κB pathway［J］. Diabetes Metab Syndr Obes Targets Ther， 2020， 13： 4495-4505. doi：10.2147/dmso.s278267 . doi: 10.2147/dmso.s278267
[6]	CRAMMOND P， HASTAK P， DELANEY A，et al. Taking its TOLL： the role of toll-like receptor 4 in human health and disease， and its potential as a therapeutic target［J］.Front Immunol，2026，17：1761361. doi： 10.3389/fimmu.2026.1761361. eCollection 2026 . doi: 10.3389/fimmu.2026.1761361. eCollection 2026
[7]	LAN C， LI Y， WENG Z， et al. TLR4 mediates lipotoxic β-cell dysfunction by inhibiting the TMEM24/PI3K/AKT pathway［J］. Acta Biochim Biophys Sin， 2025， 57（10）： 1684-1695. doi：10.3724/abbs.2025045 . doi: 10.3724/abbs.2025045
[8]	CHEN J， FEI S， CHAN L W C， et al. Inflammatory signaling pathways in pancreatic β-cell： New insights into type 2 diabetes pathogenesis［J］. Pharmacol Res， 2025， 216： 107776. doi：10.1016/j.phrs.2025.107776 . doi: 10.1016/j.phrs.2025.107776
[9]	CRAMMOND P， HASTAK P， DELANEY A， et al. Taking its TOLL： The role of toll-like receptor 4 in human health and disease， and its potential as a therapeutic target［J］. Front Immunol， 2026， 17： 1761361. doi：10.3389/fimmu.2026.1761361 . doi: 10.3389/fimmu.2026.1761361
[10]	高艳. TLR4基因甲基化对酒精性脂肪性肝炎痰瘀互结证发病机制的影响［D］. 太原：山西中医药大学， 2021.
[11]	DING T， WEN B， CHEN J， et al. Excess homocysteine inhibits pancreatic β-cell secretory function by repressing Zbtb20 expression［J］. Mol Cell Endocrinol， 2024， 586： 112195. doi：10.1016/j.mce.2024.112195 . doi: 10.1016/j.mce.2024.112195
[12]	邓玲，梁瑜祯，铁死亡与胰岛β细胞功能的研究进展.中华内科杂志，2023，62（1）： 113-116. DOI： 10.3760/cma.j.cn112138-20220502-00333 . doi: 10.3760/cma.j.cn112138-20220502-00333
[13]	CRUCIANI-GUGLIELMACCI C， MENEYROL K， DENOM J， et al. Homocysteine metabolism pathway is involved in the control of glucose homeostasis： A cystathionine beta synthase deficiency study in mouse［J］. Cells， 2022， 11（11）： 1737. doi：10.3390/cells11111737 . doi: 10.3390/cells11111737
[14]	ZHANG X， QU Y Y， LIU L， et al. Homocysteine inhibits pro-insulin receptor cleavage and causes insulin resistance via protein cysteine-homocysteinylation［J］. Cell Rep， 2021， 37（2）： 109821. doi：10.1016/j.celrep.2021.109821 . doi: 10.1016/j.celrep.2021.109821
[15]	YUAN X， DING S， ZHOU L， et al. Association between plasma homocysteine levels and pancreatic islet beta-cell function in the patients with type 2 diabetes mellitus： A cross-sectional study from China［J］. Ann Palliat Med， 2021， 10（7）： 8169-8179. doi：10.21037/apm-21-1671 . doi: 10.21037/apm-21-1671
[16]	LI Y， ZHANG H， JIANG C， et al. Hyperhomocysteinemia promotes insulin resistance by inducing endoplasmic reticulum stress in adipose tissue［J］. J Biol Chem， 2013， 288（14）： 9583-9592. doi：10.1074/jbc.M112.431627 . doi: 10.1074/jbc.M112.431627
[17]	STANCILL J S， CORBETT J A. The role of thioredoxin/peroxiredoxin in the β-cell defense against oxidative damage［J］. Front Endocrinol， 2021， 12： 718235. doi：10.3389/fendo.2021. 718235 . doi: 10.3389/fendo.2021. 718235
[18]	LENZEN S. The pancreatic beta cell： An intricate relation between anatomical structure， the signalling mechanism of glucose-induced insulin secretion， the low antioxidative defence， the high vulnerability and sensitivity to diabetic stress［J］. ChemTexts， 2021， 7（2）： 13. doi：10.1007/s40828-021-00140-3 . doi: 10.1007/s40828-021-00140-3
[19]	XUAN Y， YANG Y， SUN Y， et al. Antagonistic effects of resveratrol on reproductive injury in hind-limp unloading male rats［J］. Kjkxxb， 2024， 44（1）： 133. doi：10.11728/cjss2024.01.2023-0063 . doi: 10.11728/cjss2024.01.2023-0063
[20]	PELCZYŃSKA M， SZYMON S， KONIECZNY M， et al. Influence of certain natural bioactive compounds on glycemic control： A narrative review［J］. Nutrients， 2026， 18（1）： 52. doi：10.3390/nu18010052 . doi: 10.3390/nu18010052
[21]	KOGUT Ł， PUCHALSKI C， KATRYŃSKA D， et al. The Multidirectional Biological Activity of Resveratrol： Molecular Mechanisms， Systemic Effects and Therapeutic Potential-A Review［J］.Nutrients， 2026，18（2）：313. doi： 10.3390/nu18020313 . doi: 10.3390/nu18020313
[22]	VELA-GUAJARDO J E， GARZA-GONZÁLEZ S， GARCÍA N. Glucolipotoxicity-induced oxidative stress is related to mitochondrial dysfunction and apoptosis of pancreatic β-cell［J］. Curr Diabetes Rev， 2021， 17（5）： e031120187541. doi：10.2174/1573399816666201103142102 . doi: 10.2174/1573399816666201103142102
[23]	EGUCHI N， VAZIRI N D， DAFOE D C， et al. The role of oxidative stress in pancreatic β cell dysfunction in diabetes［J］. Int J Mol Sci， 2021， 22（4）： 1509. doi：10.3390/ijms22041509 . doi: 10.3390/ijms22041509
[24]	DINIĆ S， ARAMBAŠIĆ JOVANOVIĆ J， USKOKOVIĆ A， et al. Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management［J］. Front Endocrinol， 2022， 13： 1006376. doi：10.3389/fendo.2022.1006376 . doi: 10.3389/fendo.2022.1006376
[25]	ZHANG Y， LIANG X， BAO X， et al. Toll-like receptor 4 （TLR4） inhibitors： Current research and prospective［J］. Eur J Med Chem， 2022， 235： 114291. doi：10.1016/j.ejmech.2022. 114291 . doi: 10.1016/j.ejmech.2022. 114291
[26]	ZENG F， ZHENG J， SHEN L， et al. Physiological mechanisms of TLR4 in glucolipid metabolism regulation： Potential use in metabolic syndrome prevention［J］. Nutr Metab Cardiovasc Dis， 2023， 33（1）： 38-46. doi：10.1016/j.numecd.2022.10.011 . doi: 10.1016/j.numecd.2022.10.011
[27]	WANG X， LI K， TANG J. Acute glucose load induced islet β cells dysfunction in TLR4 dependent manner in male mice［J］. Biochem Biophys Res Commun， 2020， 524（1）： 205-210. doi：10.1016/j.bbrc.2020.01.059 . doi: 10.1016/j.bbrc.2020.01.059
[28]	KOKLESOVA L， MAZURAKOVA A， SAMEC M， et al. Homocysteine metabolism as the target for predictive medical approach， disease prevention， prognosis， and treatments tailored to the person［J］. EPMA J， 2021， 12（4）： 477-505. doi：10.1007/s13167-021-00263-0 . doi: 10.1007/s13167-021-00263-0
[29]	农茜，陆文权，梁烨，等. 同型半胱氨酸与甲基代谢及其胱硫醚酶基因研究进展［J］. 临床医学进展， 2020， 10（7）： 1277-1284. doi：10.12677/ACM.2020.107194 . doi: 10.12677/ACM.2020.107194
[30]	MOHAN K N. DNMT1： Catalytic and non-catalytic roles in different biological processes［J］. Epigenomics， 2022， 14（10）： 629-643. doi：10.2217/epi-2022-0035 . doi: 10.2217/epi-2022-0035
[31]	REN W， GAO L， SONG J. Structural basis of DNMT1 and DNMT3A-mediated DNA methylation［J］. Genes， 2018， 9（12）： 620. doi：10.3390/genes9120620 . doi: 10.3390/genes9120620
[32]	MOHAN K N， CHAILLET J R. Cell and molecular biology of DNA methyltransferase 1［J］. Int Rev Cell Mol Biol， 2013， 306： 1-42. doi： 10.1016/B978-0-12-407694-5.00001-8 . doi: 10.1016/B978-0-12-407694-5.00001-8
[33]	SINGH M， SAXENA S， MOHAN K N. DNMT1 downregulation as well as its overexpression distinctly affect mostly overlapping genes implicated in schizophrenia， autism spectrum， epilepsy， and bipolar disorders［J］. Front Mol Neurosci， 2023， 16： 1275697. doi：10.3389/fnmol.2023.1275697 . doi: 10.3389/fnmol.2023.1275697
[34]	ELDER E， LEMIEUX A， LEGAULT L M， et al. Rescuing DNMT1 fails to fully reverse the molecular and functional repercussions of its loss in mouse embryonic stem cells［J］. Nucleic Acids Res， 2025， 53（4）： gkaf130. doi：10.1093/nar/gkaf130 . doi: 10.1093/nar/gkaf130
[35]	ZHAO Z， LI L， ZENG R， et al. 5mC modification orchestrates choriogenesis and fertilization by preventing prolonged ftz-f1 expression［J］. Nat Commun， 2023， 14（1）： 8234. doi：10.1038/s41467-023-43987-5 . doi: 10.1038/s41467-023-43987-5

项目	不同浓度Hcy对应细胞活力/%	不同浓度Res对应细胞活力/%
Control	100 ± 0.00	100 ± 0.00
40 μmol/L Hcy	85.9 ± 8.39	-
80 μmol/L Hcy	77.0 ± 6.23	-
100 μmol/L Hcy	67.8 ± 9.54^*	63.0 ± 9.39^*
120 μmol/L Hcy	63.4 ± 8.25^*	-
140 μmol/L Hcy	55.8 ± 9.34	-
100 μmol/L Hcy + 2.5 μmol/L Res	-	76.7 ± 0.32
100 μmol/L Hcy + 5 μmol/L Res	-	75.0 ± 4.88
100 μmol/L Hcy + 10 μmol/L Res	-	79.3 ± 6.30^#
100 μmol/L Hcy + 20 μmol/L Res	-	79.8 ± 5.75^##
100 μmol/L Hcy + 40 μmol/L Res	-	80.9 ± 8.80^##

项目	MDA 表达量/（nmol/mgprot）	GSH-Px活性/（U/mgprot）	Insulin表达水平/（ng/mL）
Control组	0.154 ± 0.044	6.67 ± 1.120	400 ± 20.9
Hcy组	0.279 ± 0.082^**	5.52 ± 0.322^*	362 ± 36.6^*
Hcy+Res组	0.159 ± 0.040 ^##	6.55 ± 0.325 ^#	404 ± 27.7 ^#
F值	9.457	4.910	5.117
P值	0.001 9	0.022 9	0.015 5

项目	TLR4蛋白表达水平	TLR4mRNA水平
Control组	1.00 ± 0.000	1.00 ± 0.000
Hcy组	1.28 ± 0.168^*	1.11 ± 0.148^*
Hcy + Res	0.68 ± 0.096^##	0.61 ± 0.067^##
F值	29.61	59.51
P值	0.000 2	0.000 1

项目	TLR4甲基化水平	DNMT1蛋白表达水平
Control组	0.682 ± 0.019	1.000 ± 0.000
Hcy组	0.324 ± 0.009^*	0.279 ± 0.129^*
Hcy+Res组	0.578 ± 0.086^##	0.797 ± 0.154^##
F值	51.94	35.29
P值	0.000 1	0.000 1

项目	MDA表达量/（nmol/mgprot）	GSH-Px活性/（U/mgprot）	Insulin表达水平/（ng/mL）
Hcy组	0.119 ± 0.014	553 ± 234	29.8 ± 2.86
Hcy+Res组	0.060 ± 0.014^**	1 222 ± 703^*	42.7 ± 4.35^**
Hcy+si-NC组	0.085 ± 0.027	1 069 ± 215	34.1 ± 1.84
Hcy+si-DNMT1组	0.139 ± 0.019 ^##	361 ± 194 ^#	23.2 ± 2.58 ^##
Hcy+Res+si-DNMT1组	0.101 ± 0.024^§	391 ± 171^§§	27.7 ± 3.46^§§
F值	10.99	6.396	49.20
P值	0.000 1	0.001 3	0.000 1

Resveratrol alleviates homocysteine-induced oxidative damage in mouse pancreatic β-cells by regulating toll-like receptor 4 and its methylation level

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 16

References 35

Related Articles 15

Recommended Articles

Metrics

Comments

项目	MDA 表达量/（nmol/mgprot）	GSH-Px活性/（U/mgprot）	Insulin表达水平/（ng/mL）
Hcy组	1.11 ± 0.33	1.08 ± 0.657	44.1 ± 4.00
Hcy+si-NC组	1.27 ± 0.23	1.02 ± 0.500	36.5 ± 2.51
Hcy+si-TLR4组	0.95 ± 0.17^**	1.81 ± 0.349^*	42.0 ± 3.08^*
Hcy+Res+si-NC	0.84 ± 0.13	1.83 ± 0.725	41.0 ± 2.44
Hcy+Res+si-TLR4组	0.65 ± 0.13^§§#	3.81 ± 1.47^§#	46.5 ± 3.24^§##
F值	10.18	10.75	10.10
P值	0.000 1	0.000 1	0.000 1

项目	MDA 表达量/（nmol/mgprot）	GSH-Px活性/（U/mgprot）	Insulin表达水平/（ng/mL）
Res+si-NC组	0.130 ± 0.065	33.0 ± 25.1	31.3 ± 5.29
Res+si-TLR4组	0.106 ± 0.021	36.7 ± 31.9	35.1 ± 4.75
t值	0.997 0	0.275 0	1.586 0
P值	0.335 6	0.786 9	0.132 4

[1]	Gangqiang XU,Zhaosuo HU,Long WANG,Runlin YUAN,Xin CAI,Zhengxu CHEN. The application value of serum osmolality， N-terminal pro-brain natriuretic peptide， and homocysteine in the early diagnosis of acute heart failure in patients with coronary heart disease and hypertension [J]. The Journal of Practical Medicine, 2026, 42(6): 1018-1023.
[2]	Lixia ZHANG,Xuefei FAN,Suhuan CHEN,Mengyan ZHANG,Yubao SHAO,Jian ZHOU,Xiaoyu CHEN. Effect of resveratrol mediated by the PINK1/Parkin pathway on fibroblast-like synovial cells of osteoarthritis treated with H₂O₂ [J]. The Journal of Practical Medicine, 2026, 42(3): 363-370.
[3]	Ziqing WANG,Ning DING,Lianpeng YANG,Linyun WANG,Jingrui LI,Yibin WANG,Guizhong LI,Yideng JIANG,Guanjun LU. The role of circ_0001126 in Hcy-induced ferroptosis of MPC-5 cells [J]. The Journal of Practical Medicine, 2026, 42(2): 201-211.
[4]	Jun LÜ,Tang DENG,Jin PENG,Xunkai WANG,Jiangpeng WU,Guiyun JIN. Mechanism of maresin1 in alleviating lower limb ischemia-reperfusion injury by inhibiting pyroptosis via the TLR4/NF-κB/NLRP3 pathway [J]. The Journal of Practical Medicine, 2026, 42(10): 1849-1857.
[5]	Junjie ZHAI,Shaoying WEN,Xinru LI,Rui SUN,Ning QI,Qifan ZHANG,Li YANG,Hui HUANG,Lingju MA,Yinju HAO,Yideng JIANG,Guizhong LI,Shengchao. MA. Role of Toll⁃like receptor 4 in regulation of homocysteine⁃induced ferroptosis in macrophages [J]. The Journal of Practical Medicine, 2025, 41(3): 313-321.
[6]	Zhiyi CHEN,Sirui LIU,Jingxian HAN,Xuezhu. ZHANG. Interaction between DNA methylation and oxidative stress in Alzheimer′s disease： Bidirectional regulation and positive⁃feedback networks [J]. The Journal of Practical Medicine, 2025, 41(24): 3802-3808.
[7]	Debang LI,Xiaojun ZHU,Pujia. REN. Relationship between serum F2IP， Hcy， cPLA2 and male erectile dysfunction [J]. The Journal of Practical Medicine, 2025, 41(23): 3730-3736.
[8]	Hongchao SHAO,Qiyuan LUO,Wenbin GAO,Wen LUO,Mushi YE. Resveratrol inhibits prostate cancer growth and hormone resistance： An in vivo study [J]. The Journal of Practical Medicine, 2025, 41(12): 1835-1839.
[9]	Fei GAO,Jing LI,Hongjian. LI. MAPK improves intestional obstruction in pregnancy through inhibiting TLR4/Myd88/NF⁃κB pathway [J]. The Journal of Practical Medicine, 2024, 40(8): 1095-1100.
[10]	Weifeng LIU,Zheng DAI,Yibin ZHOU,Kaiwen FENG,Kai WEI,Gule SUN,Dongrong YANG,Jin. ZHU. The value of urine protein kinase Y⁃linked gene promoter site methylation in early diagnosis of prostate cancer [J]. The Journal of Practical Medicine, 2024, 40(5): 688-694.
[11]	Zhenghao ZHANG,Fang MA,Qing ZHANG,Tongtong XIA,Honglin LIU,Zhigang BAI,Guanjun LU,Jingwen ZHANG,Hongjian PENG,Yideng JIANG,Shengchao. MA. Effect of LncRNA SNHG1 on homocysteine⁃induced podocytespyrophosis [J]. The Journal of Practical Medicine, 2024, 40(4): 476-482.
[12]	Wenqing XU,Yishan LI,Qiuyu HAN,Fangjing SONG,Lin. MENG. Expression levels of HIF⁃3α methylation and DDIT4 in gestational diabetes mellitus and its relationship with pregnancy outcomes [J]. The Journal of Practical Medicine, 2024, 40(24): 3497-3502.
[13]	Suzhen CHAO,Nian ZHOU,Xinyi SHI,Yili ZHOU,Junjie XIA,Bo LIU,Mingshi REN,Zihan. LI. Effect of mangiferin on differentiation of bone marrow mesenchymal stem cells induced by homocysteine [J]. The Journal of Practical Medicine, 2024, 40(23): 3284-3290.
[14]	Gang DENG,Lixin ZHU,Jiasong GUO,Yizhou. XU. Research progress on the treatment of osteoarthritis with small molecules derived from traditional Chinese medicine：A review of literatures [J]. The Journal of Practical Medicine, 2024, 40(23): 3389-3393.
[15]	Xiaoqin LI,Lexin WANG,Xiaojun MA,Na LI,Guanjun LU,Zhihan ZHANG,Pengcheng. ZHANG. Mechanism of iron death induced by high homocysteine via TRPC6/NF⁃κb in glomerular podiatocytes [J]. The Journal of Practical Medicine, 2024, 40(2): 174-181.