Chinese Medical E-ournals Database
Adv Search
中华妇幼临床医学杂志(电子版)

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2020, Vol. 16 ›› Issue (01): 32 -41. doi: 10.3877/cma.j.issn.1673-5250.2020.01.005

Special Issue: ；

Original Article

Mechanisms of Sestrin2 regulating cell autophagy after hypoxic-ischemic brain damage in neonatal rats

Huishun Ma1, Hongju Chen1,†(), Jun Tang1   

  1. 1. Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2018-12-29 Revised:2019-08-30 Published:2020-02-01
  • Corresponding author: Hongju Chen
  • About author:
    Corresponding author: Chen Hongju, Email:
  • Supported by:
    National Natural Science Foundation of China(81501304, 81330016, 81630038, 81771634, 81842011); National Clinical Key Professional Fund(1311200003303); Youth Technology Innovation Team Fund of Sichuan Province(2016TD0002)
HTML ( ) PDF ( )
Objective

To investigate the role and mechanism of stress-inducing protein Sestrin2 in the regulation of nerve cell autophagy in neonatal rats after hypoxic-ischemic brain damage (HIBD).

Methods

Eighty postnatal 10 days newborn Sprague-Dawley rats (test rats) were selected as research subjects. For the 60 test rats, the HIBD model was established; then according to the sacrifice time of 4, 8, 12, 24, 72 h after hypoxia-ischemia (HI), 60 test rats were included into 4, 8, 12, 24, 72 h after HI group, which was 20 cases in 24 h after HI group and the rest were 10 cases in each group. For the remaining 20 test rats, the right common carotid artery was separated but not ligated, no hypoxia treatment was performed and the sacrifice time corresponded to 24 h after HI group, and they were included into sham operation group (n=20). ① After obtained hippocampal tissue samples of rats in 4, 8, 12, 24, 72 h after HI group and sham operation group (10 cases in each group), western blotting was used to detect relative expression levels of Sestrin2, liver kinase B1 (LKB1), phosphorylated LKB1 (p-LKB1), adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), autophagy-related protein Beclin1, microtubule-associated protein 1 light chain (LC)3, and apoptosis-related protein cleaved-caspase 3 (CC3) in hippocampus tissue of rats, and analysis of variance and least significant difference (LSD)-t methods were used to compare the above indicators among 6 groups or between 4, 8, 12, 24, 72 h after HI groups and sham operation group, respectively. ② After obtained cerebrum samples of remaining rats in 24 h after HI group and sham operation group (10 cases in each group), immunohistochemistry SP method was used to detect the expression levels of p-AMPK, LC3 and CC3, including integrated absorbance (IA) values and staining results in rats′ hippocampus tissue. And using t test to compare the IA values of the three indicators between two groups. This study was approved by the Animal Experimental Ethics Committee of Sichuan University [Approval No. SYXK (Chuan) 2013-185].

Results

① The results of western blotting showed that the levels of p-mTOR and CC3 in rats′ hippocampus tissue of 4 h and 8 h after HI groups were higher than those in sham operation group, respectively; the levels of Sestrin2, p-LKB1, p-AMPK, p-mTOR, Beclin1, LC3 and CC3 in rats′ hippocampus tissue of 12 h and 24 h after HI groups were higher than those in sham operation group, respectively; the levels of Sestrin2 and CC3 in rats′ hippocampus tissue of 72 h group after HI group were higher than those in sham operation group; and all of these differences were statistically significant (P<0.05). Among them, the level of p-mTOR was the highest in rats′ hippocampus tissue of 8 h after HI group; and the highest levels of Sestrin2, p-LKB1, p-AMPK, Beclin1, LC3 and CC3 in rats′ hippocampus tissue were all in 24 h after HI group. There were no significant differences among 6 groups, also between 4, 8, 12, 24, 72 h after HI groups with sham operation group, respectively, in levels of LKB1, AMPK and mTOR in rats′ hippocampus tissue (P>0.05). ② IA value detected results of immunohistochemical SP method showed that the expression levels of p-AMPK, LC3 and CC3 in rats′ hippocampus tissue of 24 h after HI group were (24 106±2 393), (41 892±4 094), (61 670±4 696), respectively, which were higher than those of (15 593±1 575), (18 941±2 131) and (20 279±1 912) in sham operation group, and the differences were statistically significant (t=9.398, P=0.035; t=15.723, P<0.001; t=25.812, P<0.001). Immunohistochemical SP method staining results showed that the expression level of p-AMPK, LC3 and CC3 positive cells were higher in rats′ hippocampus tissue of 24 h after HI group.

Conclusion

When HIBD occurs in postnatal 10 days newborn SD rats, the Sestrin2 in hippocampus tissue may be involved in the regulation of nerve cell autophagy and apoptosis via LKB1/AMPK/mTOR signaling pathway.

Key words: Sestrin 2 protein, rat, Signal transduction, Hypoxia-ischemia, brain, Autophagy, Apoptosis, Blotting, western, Rats, Sprague-Dawley, Animals, newborn
表1 6组受试鼠海马组织中各蛋白相对表达量比较(±s)
组别 鼠数 Sestrin2 LKB1 p-LKB1 AMPK p-AMPK
①HI后4 h组 10 0.21±0.03 1.44±0.11 0.44±0.09 1.90±0.18 0.51±0.08
②HI后8 h组 10 0.19±0.03 1.39±0.08 0.38±0.07 1.79±0.10 0.45±0.06
③HI后12 h组 10 0.41±0.06 1.48±0.13 0.70±0.10 1.89±0.17 0.80±0.06
④HI后24 h组 10 0.50±0.06 1.41±0.14 1.09±0.12 1.80±0.19 1.01±0.09
⑤HI后72 h组 10 0.40±0.06 1.37±0.14 0.53±0.08 1.78±0.12 0.66±0.09
⑥假手术组 10 0.17±0.03 1.38±0.11 0.39±0.07 1.76±0.12 0.45±0.05
总体比较 ? ? ? ? ? ?
? F值 ? 82.781 1.154 93.335 1.360 92.327
? P值 ? <0.001 0.344 <0.001 0.254 <0.001
多重比较的P值a ? ? ? ? ? ?
? ① vs ⑥ ? 0.052 0.254 0.222 0.059 0.133
? ② vs ⑥ ? 0.252 0.835 0.802 0.663 0.903
? ③ vs ⑥ ? 0.023 0.082 0.034 0.082 0.025
? ④ vs ⑥ ? 0.014 0.545 0.018 0.562 0.013
? ⑤ vs ⑥ ? 0.025 0.818 0.086 0.847 0.076
组别 鼠数 mTOR p-mTOR Beclin1 LC3 CC3
①HI后4 h组 10 1.34±0.09 0.44±0.06 0.23±0.04 0.33±0.04 0.29±0.04
②HI后8 h组 10 1.29±0.15 0.83±0.07 0.20±0.07 0.31±0.05 0.36±0.06
③HI后12 h组 10 1.27±0.12 0.61±0.05 0.37±0.07 0.61±0.04 0.51±0.05
④HI后24 h组 10 1.23±0.11 0.55±0.07 0.63±0.05 0.76±0.06 0.69±0.08
⑤HI后72 h组 10 1.25±0.09 0.38±0.04 0.30±0.06 0.53±0.07 0.50±0.06
⑥假手术组 10 1.26±0.14 0.36±0.05 0.19±0.03 0.29±0.03 0.22±0.04
总体比较 ? ? ? ? ? ?
? F值 ? 0.898 85.534 88.384 143.492 82.375
? P值 ? 0.490 <0.001 <0.001 <0.001 <0.001
多重比较的P值a ? ? ? ? ? ?
? ① vs ⑥ ? 0.138 0.011 0.117 0.121 0.014
? ② vs ⑥ ? 0.575 <0.001 0.580 0.438 <0.001
? ③ vs ⑥ ? 0.751 <0.001 0.044 0.036 <0.001
? ④ vs ⑥ ? 0.696 <0.001 <0.001 <0.001 <0.001
? ⑤ vs ⑥ ? 0.928 0.562 0.068 0.057 <0.001
图1 6组受试鼠海马组织中各蛋白电泳图(蛋白质印迹法)
表2 2组受试鼠海马组织中p-AMPK、LC3及CC3积分吸光度值比较(±s)
组别 鼠数 p-AMPK LC3 CC3
HI后24 h组 10 24 106±2 393 41 892±4 094 61 670±4 696
假手术组 10 15 593±1 575 18 941±2 131 20 279±1 912
t值 ? 9.398 15.723 25.812
P值 ? 0.035 <0.001 <0.001
图2 10日龄SD大鼠海马组织免疫组织化学图(SP法，高倍镜)[图2A、2B、2C分别为HI后24 h组p-AMPK、LC3、CC3呈阳性的细胞表达水平较高(箭头所示)；图2D、2E、2F分别为假手术组p-AMPK、LC3、CC3呈阳性的细胞均为微量表达]
[1]
Nasiell J, Papadogiannakis N, Löf E, et al. Hypoxic ischemic encephalopathy in newborns linked to placental and umbilical cord abnormalities[J]. J Matern Fetal Neonatal Med, 2016, 29(5)：721-726. DOI: 10.3109/14767058.2015.1015984.
[2]
Chen H, Qu Y, Tang B, et al. Role of mammalian target of rapamycin in hypoxic or ischemic brain injury: potential neuroprotection and limitations[J]. Rev Neurosci, 2012, 23(3)：279-287. DOI: 10.1515/revneuro-2012-0001.
[3]
Puyal J, Ginet V, Grishchuk Y, et al. Neuronal autophagy as a mediator of life and death: contrasting roles in chronic neurodegenerative and acute neural disorders[J]. Neuroscientist, 2012, 18(3)：224-236. DOI: 10.1177/1073858411404948.
[4]
Chen H, Xiong T, Qu Y, et al. mTOR activates hypoxia-inducible factor-1α and inhibits neuronal apoptosis in the developing rat brain during the early phase after hypoxia-ischemia[J]. Neurosci Lett, 2012, 507(2)：118-123. DOI: 10.1016/j.neulet.2011.11.058.
[5]
Chang HW, Lee YS, Nam HY, et al. Knockdown of β-catenin controls both apoptotic and autophagic cell death through LKB1/AMPK signaling in head and neck squamous cell carcinoma cell lines[J]. Cell Signal, 2013, 25(4)：839-847. DOI: 10.1016/j.cellsig.2012.12.020.
[6]
Xiao X, He Q, Lu C, et al. Metformin impairs the growth of liver kinase B1-intact cervical cancer cells[J]. Gynecol Oncol, 2012, 127(1)：249-255. DOI: 10.1016/j.ygyno.2012.06.032.
[7]
Budanov AV, Sablina AA, Feinstein E, et al. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD[J]. Science, 2004, 304(5670)：596-600. DOI: 10.1126/science.1095569.
[8]
Budanov AV, Karin M. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling[J]. Cell, 2008, 134(3)：451-460. DOI: 10.1016/j.cell.2008.06.028.
[9]
Peng M, Yin N, Li MO. Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling[J]. Cell, 2014, 159(1)：122-133. DOI: 10.1016/j.cell.2014.08.038.
[10]
Maiuri MC, Malik SA, Morselli E, et al. Stimulation of autophagy by the p53 target gene Sestrin2[J]. Cell Cycle, 2009, 8(10)：1571-1576. DOI: 10.4161/cc.8.10.8498.
[11]
Rice JE 3rd, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat[J]. Ann Neurol, 1981, 9(2)：131-141. DOI: 10.1002/ana.410090206.
[12]
李丽华，屈艺，刘红卫，等. 足月新生儿缺氧缺血性脑损伤大鼠模型的制作与鉴定[J]. 中国实验动物学报，2009, 17(4)：3. DOI: 10.3969/j.issn.1005-4847.2009.04.006.
[13]
Kurien BT, Scofield RH. Western blotting: an introduction[J]. Methods Mol Biol, 2015, 1312：17-30. DOI: 10.1007/978-1-4939-2694-7_5.
[14]
Tamargo-Gómez I, Mariño G. AMPK: regulation of metabolic dynamics in the context of autophagy[J]. Int J Mol Sci, 2018, 19(12)：3812. DOI: 10.3390/ijms19123812.
[15]
Villanueva-Paz M, Cotán D, Garrido-Maraver J, et al. AMPK regulation of cell growth, apoptosis, autophagy, and bioenergetics[J]. Exp Suppl, 2016, 107：45-71. DOI: 10.1007/978-3-319-43589-3_3.
[16]
Jiang S, Li T, Ji T, et al. AMPK: potential therapeutic target for ischemic stroke[J]. Theranostics, 2018, 8(16)：4535-4551. DOI: 10.7150/thno.25674.
[17]
陈子馨，吴璥，王石麟，等. 神经免疫组织化学的基本技术[J]. 中华病理学杂志，1996, 25(6): 385-386.
[18]
Yang Z, Zhong L, Zhong S, et al. Hypoxia induces microglia autophagy and neural inflammation injury in focal cerebral ischemia model[J]. Exp Mol Pathol, 2015, 98(2)：219-224. DOI: 10.1016/j.yexmp.2015.02.003.
[19]
Pan R, Timmins GS, Liu W, et al. Autophagy mediates astrocyte death during zinc-potentiated ischemia--reperfusion injury[J]. Biol Trace Elem Res, 2015, 166(1)：89-95. DOI: 10.1007/s12011-015-0287-6.
[20]
Ginet V, Pittet MP, Rummel C, et al. Dying neurons in thalamus of asphyxiated term newborns and rats are autophagic[J]. Ann Neurol, 2014, 76(5)：695-711. DOI: 10.1002/ana.24257.
[21]
Zheng Z, Zhang L, Qu Y, et al. Mesenchymal stem cells protect against hypoxia-ischemia brain damage by enhancing autophagy through brain derived neurotrophic factor/mammalin target of rapamycin signaling pathway[J]. Stem Cells, 2018, 36(7)：1109-1121. DOI: 10.1002/stem.2808.
[22]
Wang J, Qi Q, Feng Z, et al. Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway[J]. Oncotarget, 2016, 7(41)：66944-66958. DOI: 10.18632/oncotarget.11396.
[23]
Wang B, Cheng KK. Hypothalamic AMPK as a mediator of hormonal regulation of energy balance[J]. Int J Mol Sci, 2018, 19(11). DOI: 10.3390/ijms19113552.
[24]
Chu X, Cao L, Yu Z, et al. Hydrogen-rich saline promotes microglia M2 polarization and complement-mediated synapse loss to restore behavioral deficits following hypoxia-ischemic in neonatal mice via AMPK activation[J]. J Neuroinflammation, 2019, 16(1)：104. DOI: 10.1186/s12974-019-1488-2.
[25]
Ma RD, Zhou GJ, Qu M, et al. Corticosterone induces neurotoxicity in PC12 cells via disrupting autophagy flux mediated by AMPK/mTOR signaling[J]. CNS Neurosci Ther, 2019. DOI：10.1111/cns.13212. [Epub ahead of print]．
[26]
Zhao H, Chen S, Gao K, et al. Resveratrol protects against spinal cord injury by activating autophagy and inhibiting apoptosis mediated by the SIRT1/AMPK signaling pathway[J]. Neuroscience, 2017, 348：241-251. DOI: 10.1016/j.neuroscience.2017.02.027.
[27]
Park HW, Park H, Ro SH, et al. Hepatoprotective role of Sestrin2 against chronic ER stress[J]. Nat Commun, 2014, 5：4233. DOI: 10.1038/ncomms5233.
[28]
Kumar A, Shaha C. SESN2 facilitates mitophagy by helping Parkin translocation through ULK1 mediated Beclin1 phosphorylation[J]. Sci Rep, 2018, 8(1)：615. DOI: 10.1038/s41598-017-19102-2.
[29]
Ambrosio S, Saccà CD, Amente S, et al. Lysine-specific demethylase LSD1 regulates autophagy in neuroblastoma through SESN2-dependent pathway[J]. Oncogene, 2017, 36(48)：6701-6711. DOI: 10.1038/onc.2017.267.
[30]
Li H, Liu S, Yuan H, et al. Sestrin 2 induces autophagy and attenuates insulin resistance by regulating AMPK signaling in C2C12 myotubes[J]. Exp Cell Res, 2017, 354(1)：18-24. DOI: 10.1016/j.yexcr.2017.03.023.
[31]
Hou YS, Guan JJ, Xu HD, et al. Sestrin2 protects dopaminergic cells against rotenone toxicity through AMPK-dependent autophagy activation[J]. Mol Cell Biol, 2015, 35(16)：2740-2751. DOI: 10.1128/MCB.00285-15.
[32]
Jegal KH, Ko HL, Park SM, et al. Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress[J]. Apoptosis, 2016, 21(5)：642-656. DOI: 10.1007/s10495-016-1233-6.
[33]
Pasha M, Eid AH, Eid AA, et al. Sestrin2 as a novel biomarker and therapeutic target for various diseases[J]. Oxid Med Cell Longev, 2017, 2017：3296294. DOI: 10.1155/2017/3296294.
[34]
Kim SJ, Kim KM, Yang JH, et al. Sestrin2 protects against acetaminophen-induced liver injury[J]. Chem Biol Interact, 2017, 269：50-58. DOI: 10.1016/j.cbi.2017.02.002.
[35]
Seo K, Seo S, Han JY, et al. Resveratrol attenuates methylglyoxal-induced mitochondrial dysfunction and apoptosis by Sestrin2 induction[J]. Toxicol Appl Pharmacol, 2014, 280(2)：314-322. DOI: 10.1016/j.taap.2014.08.011.
[36]
Hwang HJ, Kim JW, Chung HS, et al. Knockdown of Sestrin2 increases lipopolysaccharide-induced oxidative stress, apoptosis, and fibrotic reactions in H9c2 cells and heart tissues of mice via an AMPK-dependent mechanism[J]. Mediators Inflamm, 2018, 2018：6209140. DOI: 10.1155/2018/6209140.
[37]
Hu HJ, Shi ZY, Lin XL, et al. Upregulation of Sestrin2 expression protects against macrophage apoptosis induced by oxidized low-density lipoprotein[J]. DNA Cell Biol, 2015, 34(4)：296-302. DOI: 10.1089/dna.2014.2627.
[38]
Chuang YC, Yang JL, Yang DI, et al. Roles of Sestrin2 and ribosomal protein S6 in transient global ischemia-induced hippocampal neuronal injury[J]. Int J Mol Sci, 2015, 16(11)：26406-26416. DOI: 10.3390/ijms161125963.
[39]
Xia J, Zeng W, Xia Y, et al. Cold atmospheric plasma induces apoptosis of melanoma cells via Sestrin2-mediated nitric oxide synthase signaling[J]. J Biophotonics, 2019, 12(1)：e201800046. DOI: 10.1002/jbio.201800046.
[40]
Ding B, Parmigiani A, Yang C, et al. Sestrin2 facilitates death receptor-induced apoptosis in lung adenocarcinoma cells through regulation of XIAP degradation[J]. Cell Cycle, 2015, 14(20)：3231-3241. DOI: 10.1080/15384101.2015.1084447.
[41]
Kim GT, Lee SH, Kim YM. Quercetin regulates Sestrin2-AMPK-mTOR signaling pathway and induces apoptosis via increased intracellular ROS in HCT116 colon cancer cells[J]. J Cancer Prev, 2013, 18(3)：264-270. DOI: 10.15430/jcp.2013.18.3.264.
[42]
Morrison A, Chen L, Wang J, et al. Sestrin2 promotes LKB1-mediated AMPK activation in the ischemic heart[J]. FASEB J, 2015, 29(2)：408-417. DOI: 10.1096/fj.14-258814.
[43]
Videla LA, Vargas R, Riquelme B, et al. Thyroid hormone-induced expression of the hepatic scaffold proteins Sestrin2, β-Klotho, and FRS2α in relation to FGF21-AMPK signaling[J]. Exp Clin Endocrinol Diabetes, 2018, 126(3)：182-186. DOI: 10.1055/s-0043-115533.
[44]
Quan N, Sun W, Wang L, et al. Sestrin2 prevents age-related intolerance to ischemia and reperfusion injury by modulating substrate metabolism[J]. FASEB J, 2017, 31(9)：4153-4167. DOI: 10.1096/fj.201700063R.
[1] Kang Li, Liang Ji, Wei Zhao, Lemin Lin. Dual role of autophagy in biological progression of breast cancer[J]. Chinese Journal of Breast Disease(Electronic Edition), 2023, 17(04): 195-202.
[2] Yingying Kong, Lutao Xie, Xiaochi Lu, Jiefeng Xu, Guangju Zhou, Mao Zhang. Protective effect and mechanism of sodium butyrate on cardio-brain injury after cardiac arrest resuscitation in pigs[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2023, 16(05): 355-362.
[3] Xiaoyan Zhang, Dongqiong Xiao, Hu Gao, Lin Chen, Fajuan Tang, Xihong Li. The protective effect and mechanism of overexpression of transcription factor 12 on the cerebral cortex of rats with sepsis-associated encephalopathy[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 540-549.
[4] Xingchen Liu, Juan Liu, Baobao Wei, Jie Liu, Hui Liu. Correlation analysis of abnormal expression of XIAP and XAF1 with ovarian cancer[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(04): 419-427.
[5] Zihui Zhou, Gongchi Li, Binghui Li, Zhi Wang, Huizhen Liu, Hui Wang, Lijun Zou. Advances of autophagy in wound healing[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2023, 18(06): 542-546.
[6] Linfeng He, Yu Cao, Ning Zhang, Xinze Ran, Fengchao Wang. Regulation of intestinal stem cells and tissue damage and repair after radiation exposure[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2023, 18(04): 358-363.
[7] Shuoru Liu, Gongwei Wang, Bin Zhang, Shuhao Li, Cheng Hu. Oncolytic virus M1 activates endoplasmic reticulum stress pathway to induce apoptosis of prostate cancer cells[J]. Chinese Journal of Endourology(Electronic Edition), 2023, 17(04): 388-393.
[8] Chunwen Deng, Song Chen, Pei Zhong, Shiqiang Min, Jian Wan. LncRNA CRNDE regulates lipopolysaccharide-induced inflammatory response and apoptosis in human alveolar epithelial cells via miR-181a-5p/SOX6 axis[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(03): 129-136.
[9] Hui Yu, Jing Wang, Dan Du, Fan Yang. Mechanism of miR-301a-3p in proliferation and apoptosis of human ovarian granulosa KGN cells[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(03): 137-143.
[10] Di Yu, Haibo Yu, Huancheng Wu, Yuming Li, Bin Su, Xin Chen. Effect of differential expression of hairy and enhancer of split homolog-1 on cholesterol-stimulated vascular endothelial cells[J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2023, 13(05): 264-270.
[11] Xiaohong Wang, Jing Qian, Wenjun Weng, Guoxiong Zhou, Shunxing Zhu, Xiaoming Qi, Chun Liu, Ping Wang, Wei Shen, Ruizhi Cheng, Jinghao Qin. Effects of regulation of nuclear factor-κB signal by mercaptopyruvate sulfurtransferase mediated autophagy on rats with severe acute pancreatitis and its mechanism[J]. Chinese Journal of Digestion and Medical Imageology(Electronic Edition), 2023, 13(06): 422-426.
[12] Shidong Deng, Lingzhi Liu, Dayong Guo, Chao Wang, Zhongxin Huang, Huihui Zhang. Effects of SNHG1 gene silencing on proliferation, apoptosis, migration, and ferroptosis of bladder cancer cells[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(07): 804-811.
[13] Minjie Zhang, Xiaoshan Zhang, Shasha Duan, Yilu Shi, Jie Zhao, Tianhao Bai, Yaxi Wang. Hydrogen for treatment of myocardial ischemia-reperfusion injury: mechanism and prospect[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(06): 744-748.
[14] Ruye Guo, Liming Meng, Nan Chen, Yuying Song, Haiyan Yin, Yan Guo. Research status on the neuroprotective efficacy and mechanism of Apelin/APJ system in Parkinson disease model[J]. Chinese Journal of Diagnostics(Electronic Edition), 2023, 11(04): 276-282.
[15] Tian Qiu, Miaojuan Yang, Bo Hu, Yi Guo, Yitao He. Research progress on the mechanism of mild hypothermia therapy for cerebral infarction[J]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2023, 17(05): 518-521.
Viewed
Full text


Abstract

Copyright © Chinese Medical Association, Chinese Medical Multimedia Press  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号