JAK2-STAT3信号通路在缺血性疾病的研究进展
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摘要
JAK2-STAT3信号途径是参与机体的分化、侵袭、代谢、血管再生的重要信号途径,多种因子及药物可通过激活此通路促进血管内皮细胞新生,改善缺血,而广泛用于基础实验及缺血性疾病的研究,本文将综述近年来JAK2-STAT3信号途径在心、脑、外周血管及其他缺血性疾病等方面进行的研究。
JAK2-STAT3 is an important signaling pathway which is involved in the differentiation, invasion, metabolism and angiogenesis in human body. A variety of factors and drugs are widely used in the research on ischemic diseases by activating this pathway to promote vascular endothelial cell neovascularization and to improve ischemia symptoms. This article reviews recent studies on the roles of JAK2-STAT3 signaling pathway in heart, brain, peripheral blood vessels and other ischemic diseases.
JAK2-STAT3 is an important signaling pathway which is involved in the differentiation, invasion, metabolism and angiogenesis in human body. A variety of factors and drugs are widely used in the research on ischemic diseases by activating this pathway to promote vascular endothelial cell neovascularization and to improve ischemia symptoms. This article reviews recent studies on the roles of JAK2-STAT3 signaling pathway in heart, brain, peripheral blood vessels and other ischemic diseases.
引文
1.Fuglesteg BN,Suleman N,Tiron C,et al.Signal transducer and activator of transcription 3 is involved in the cardioprotective signalling pathway activated by insulin therapy at reperfusion[J].Basic Res Cardiol,2008,103(5):444-453.
2.Cai B,Cai JP,Luo YL,et al.The specific roles of JAK/STAT signaling pathway in sepsis[J].Inflammation,2015,38(4):1599-1608.
3.Musso T,Johnston JA,Linnekin D,et al.Regulation of JAK3 expression in human monocytes:phosphorylation in response to interleukins 2,4,and 7[J].J Exp Med,1995,181(4):1425-1431.
4.Ikezoe T,Kojima S,Furihata M,et al.Expression of p-JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia[J].Int J Cancer,2011,129(10):2512-2521.
5.Kacimi R,Giffard RG,Yenari MA.Endotoxin-activated microglia injure brain derived endothelial cells via NF-κB,JAK-STAT and JNK stress kinase pathways[J].J Inflamm(Lond),2011,8:7.
6.Meyer SC,Keller MD,Chiu S,et al.CHZ868,a type II JAK2 inhibitor,reverses type I JAK inhibitor persistence and demonstrates e?cacy in myeloproliferative neoplasms[J].Cancer Cell,2015,28(1):15-28.
7.赵亚玲,刘贵敏,张丽军,等.JAK2/STAT信号通路抑制剂与恶性血液病[J].中国实验血液学杂志,2016,24(4):1275-1279.ZHAO Yaling,LIU Guimin,ZHANG Lijun,et al.Inhibitors of JAK2/STAT signaling pathway and hematologic malignancies-review[J].Journal of Experimental Hematology,2016,24(4):1275-1279.
8.Levy DE,Darnel JE Jr.Stats:transcriptional control and biological impact[J].Nat Rev Mol Cell Biol,2002,3(9):651-662.
9.Mitchell TJ,John S.Signal transducer and activator of transcription(STAT)signaling and T-cell lymphomas[J].Immunology,2005,114(3):301-312.
10.Schindler C,Plumlee C.Interferons pen the JAK-STAT pathway[J].Semin Cell Dev Biol,2008,19(4):311-318.
11.Guerriero ML,Dudka A,Underhill-Day N,et al.Narrative-based computational modeling of theGp130/JAK/STAT signaling pathway[J].BMC Syst Biol,2009,3:40.
12.Yang E,Henriksen MA,Schaefer O,et al.Dissociation time from DNAdetermines transcriptional function in a STAT1 linker mutant[J].J Biol Chem,2002,277(16):13455-13462.
13.Hung MH,Tai W T,Shiau CW,et al.Downregulation of signal transducer and activator of transcription 3 by sorafenib:a novel mechanism for hepatocellular carcinoma therapy[J].World JGastroenterol,2014,20(41):15269-15274.
14.Qi J,Xia G,Huang CR,et al.JSI-124(cucurbitacin i)inhibits tumor angiogenesis of human breast cancer through reduction of STAT3phosphorylation[J].Am J Chin Med,2015,43(2):337-347.
15.Su JC,Tseng PH,Wu SH,et al.SC-2001 overcomes STAT3-mediated sorafenib resistance through RFX-1/SHP-1 activation in hepatocellular carcinoma[J].Neoplasia,2014,16(7):595-605.
16.Kim DJ,Tremblay ML,Digiovanni J.Protein tyrosine phosphatases,TC-PTP,SHP1,and SHP2,cooperate in rapid dephosphorylation of Stat3 in keratinocytes following UVB irradiation[J].PLoS One,2010,5(4):e10290.
17.Okada S.Conditional ablation of stat3/socs3 discloses the dual role for reactive astrocytes after spinal cord injury[J].Nat Med,2006,12(7):829.
18.杨柳,陈蓓蕾,于海龙,等.JAK2/STAT3信号通路与脑缺血-再灌注损伤相关性的研究进展[J].东南大学学报:医学版,2018,37(1):169-173.YANG Liu,CHEN Beilei,YU Hailong,et al.Research progress of JAK2-STAT3 signal pathway and cerebra ischemia-reperfusion injury[J].Journal of Southeast University.Medical Edition,2018,37(1):169-173.
19.Brooks AJ,Dai W,O’Mara ML,et al.Mechanism of activation of protein kinase JAK2 by the growth hormone receptor[J].Science,2014,344(6185):1249783.
20.Aggarwal BB,Kunnumakkara AB,Harikumarmr KB,et al.Sigal transducer and activator of transcription-3,inflammation,and cancer:how intimate is the relationship[J].Ann N Y Acad Sci,2009,1171:59-76.
21.Gri?th LG,Naughton G.Tissue engineering-current challenges and expanding opportunities[J].Science,2002,295(5557):1009-1014.
22.Nomi M,Atala A,Coppi PD,et al.Principals of neovascularization for tissue engineering[J].Mol Aspects Med,2002,23(6):463-483.
23.Anagnostou A,Liu Z,Steiner M,et al.Erythropoietin receptor mRNAexpression in human endothelial cells[J].Proc Natl Acad Sci U S A,1994,91(9):3974-3978.
24.Nak ano M,Satoh K,Fukumoto Y,et al.Impor tant role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice[J].Circ Res,2007,100(5):662-669.
25.Ribatti D,Presta M,Vacca A,et al.Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo[J].Blood,1999,93(8):2627-2636.
26.Lloyd-Jones D,Adams RJ,Brown TM,et al.Executive summary:heart disease and stroke statistics-2010 update:a report from the American Heart Association[J].Circulation,2010,121(7):948-954.
27.Ch en YC,Wu J,Yang,ST,e t a l.St ro ke,ang i o gen es i s an d phytochemicals[J].Front Biosci(Schol Ed),2012,4:599-610.
28.Zhang J,Chopp M.Cell-based therapy for ischemic stroke[J].Expert Opin Biol Ther,2013,13(9):1229-1240.
29.Juul S.Erythropoietin in the central nervous system,and its use to prevent hypoxic-ischemic brain damage[J].Acta Paediatr Suppl,2002,91(438):36-42.
30.Sola A,Rogido M,Lee BH,et al.Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats[J].Pediatr Res,2005,57(4):481-487.
31.Raible DJ,Frey LC,Brooks-Kayal AR.Effects of JAK2-STAT3 signaling after cerebral insults[J].JAKSTAT,2014,3:e29510.
32.Dong W,Xian Y,Yuan W,et al.Catalpol stimulates VEGF production via the JAK2-STAT3 pathway to improve angiogenesis in rats’stroke model[J].J Ethnopharmacol,2016,191:169-179.
33.Zhao J,Li G,Zhang Y,et al.The potential role of JAK2-STAT3 pathway on the anti-apoptotic effect of recombinant human erythropoietin(rhEPO)after experimental traumatic brain injury of rats[J].Cytokine,2011,56(2):343-350.
34.Liu J,Naasimhan P,Yu F,et al.Neuroprotection by hy pox ic preconditioning involves oxidative stress-mediated expression of hypoxia-inducible factor and erythropoietin[J].Stroke,2005,36(6):1264-1269.
35.Li L,Li H,Li M.Curcumin protects against cerebral ischemiareperfusion injury by activating JAK2-STAT3 signaling pathway in rats[J].Int J Clin Exp Med,2015,8(9):14985.
36.Xuan YT,Guo Y,Han H,et al.An essential role of the JAK-STATpathway in ischemic preconditioning[J].Proc Natl Acad Sci U S A,2001,98(16):9050-9055.
37.Xie XJ,Fan DM,Xi K,et al.Suppression of microRNA-135b-5p protects against myocardial ischemia/reperfusion injury by activating JAK2-STAT3 signaling pathway in mice during sevoflurane anesthesia[J].Biosci Rep,2017,37(3):186-196.
38.Zhao ZQ,Corvera JS,Halkos ME,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Circ Physiol,2003,285(2):H579-H588.
39.夏大川,田轶魁,吴志浩,等.JAK2-STAT3通路介导缺血后处理心肌保护作用的初步研究[J].天津医药,2010,38(1):43-45.XIA Dachuan,TIAN Yikui,WU Zhihao,et al.Role of the JAK2-STAT3 pathway mediates the cardioprotection of ischemic postconditioning[J].Tianjin Medical Journal,2010,38(1):43-45.
40.Negoro S,Kunisada K,Fujio Y,et al.Activation of signal transducer and activator of transcription 3 protects cardiomyocytes from hy pox ia/reoxygenation-induced ox idative stress through the upregulation of manganese superoxide dismutase[J].Circulation,2001,104(9):979-981.
41.Kalka C,Masuda H,Takahashi T,et al.Vascular endothelial growth factor(165)gene transfer augments circulating endothelial progenitor cells in human subjects[J].Circ Res,2000,86(12):1198-1202.
42.Arras M,Ito WD,Scholz D,et al.Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb[J].J Clin Invest,1998,101(1):40-50.
43.黄伟彬,吕磊,张岚.JAK/STAT信号通路在动脉粥样硬化中的作用[J].上海交通大学学报:医学版,2013,33(4):506-509.HUANG Weibin,LüLei,ZHANG Lan.Effect of JAK/STAT pathway in atherosclerosis[J].Journal of Shanghai Jiao Tong University.Medical Science,2013,33(4):506-509.
44.Neeli I,Liu Z,Dronadula N,et al.An essential role of the Jak-2/STAT-3/cytosolic phospholipase A(2)axis in platelet-derived growth factor BB-induced vascular smooth muscle cell motility[J].J Biol Chem,2004,279(44):46122-46128.
45.Zhang C,Zhao YX,Zhang YH,et al.Angiotensin-converting enzyme2 attenuates atherosclerotic lesions by targeting vascular cells[J].Proc Natl Acad Sci U S A,2010,107(36):15886-15891.
46.Jay DB,Papaharalambus CA,Seidel-Rogol B,et al.Nox5 mediates PDGF-induced proliferation in human aortic smooth muscle cells[J].Free Radic Biol Med,2008,45(3):329-335.
47.朱彬蔚,卞蓉蓉,陈冬平,等.HIPK2基因对缺氧复氧诱导的NRK-52E肾小管上皮细胞活力和凋亡及JAK2/STAT3信号通路的影响[J].中国病理生理杂志,2018,34(6):1075-1080.ZHU Binwei,BIAN Rongrong,CHEN Dongping,et al.Effect of HIPK2 gene on viability,apoptosis and JAK2/STAT3 signaling pathway in NRK-52E renal tubular epithelial cells induced by hypoxia and reoxygenation[J].Chinese Journal of Pathophysiology,2018,34(6):1075-1080.
48.Fan Y,Wang N,Chuang P,et al.Role of HIPK2 in kidney fibrosis[J].Kidney Int Suppl(2011),2014,4(1):97-101.
49.吕娟,曹兰秀.当归黄芪汤对糖尿病大鼠肾组织JAK2STAT3信号通路的影响[J].中国药业,2018,27(15):9-11.LüJuan,CAO Lanxiu.Effect of Danggui Huangqi Decoction on JAK2-STAT3 signaling pathway in renal tissue of diabetic rats[J].China Pharmaceuticals,2018,27(15):9-11.
50.严栋梁,邵伟斌,葛创,等.川芎嗪对刀豆蛋白A诱导的小鼠肝纤维化JAK2/STAT3信号通路的影响[J].肝脏,2018,23(3):255-259.YAN Dongliang,SHAO Weibin,GE Chuang,et al.Effect of tetramethyl pyrazine on JAK2-STAT3 signaling pathway induced by concanavalin Ain liver fibrosis in rats[J].Chinese Hepatology,2018,23(3):255-259.
2.Cai B,Cai JP,Luo YL,et al.The specific roles of JAK/STAT signaling pathway in sepsis[J].Inflammation,2015,38(4):1599-1608.
3.Musso T,Johnston JA,Linnekin D,et al.Regulation of JAK3 expression in human monocytes:phosphorylation in response to interleukins 2,4,and 7[J].J Exp Med,1995,181(4):1425-1431.
4.Ikezoe T,Kojima S,Furihata M,et al.Expression of p-JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia[J].Int J Cancer,2011,129(10):2512-2521.
5.Kacimi R,Giffard RG,Yenari MA.Endotoxin-activated microglia injure brain derived endothelial cells via NF-κB,JAK-STAT and JNK stress kinase pathways[J].J Inflamm(Lond),2011,8:7.
6.Meyer SC,Keller MD,Chiu S,et al.CHZ868,a type II JAK2 inhibitor,reverses type I JAK inhibitor persistence and demonstrates e?cacy in myeloproliferative neoplasms[J].Cancer Cell,2015,28(1):15-28.
7.赵亚玲,刘贵敏,张丽军,等.JAK2/STAT信号通路抑制剂与恶性血液病[J].中国实验血液学杂志,2016,24(4):1275-1279.ZHAO Yaling,LIU Guimin,ZHANG Lijun,et al.Inhibitors of JAK2/STAT signaling pathway and hematologic malignancies-review[J].Journal of Experimental Hematology,2016,24(4):1275-1279.
8.Levy DE,Darnel JE Jr.Stats:transcriptional control and biological impact[J].Nat Rev Mol Cell Biol,2002,3(9):651-662.
9.Mitchell TJ,John S.Signal transducer and activator of transcription(STAT)signaling and T-cell lymphomas[J].Immunology,2005,114(3):301-312.
10.Schindler C,Plumlee C.Interferons pen the JAK-STAT pathway[J].Semin Cell Dev Biol,2008,19(4):311-318.
11.Guerriero ML,Dudka A,Underhill-Day N,et al.Narrative-based computational modeling of theGp130/JAK/STAT signaling pathway[J].BMC Syst Biol,2009,3:40.
12.Yang E,Henriksen MA,Schaefer O,et al.Dissociation time from DNAdetermines transcriptional function in a STAT1 linker mutant[J].J Biol Chem,2002,277(16):13455-13462.
13.Hung MH,Tai W T,Shiau CW,et al.Downregulation of signal transducer and activator of transcription 3 by sorafenib:a novel mechanism for hepatocellular carcinoma therapy[J].World JGastroenterol,2014,20(41):15269-15274.
14.Qi J,Xia G,Huang CR,et al.JSI-124(cucurbitacin i)inhibits tumor angiogenesis of human breast cancer through reduction of STAT3phosphorylation[J].Am J Chin Med,2015,43(2):337-347.
15.Su JC,Tseng PH,Wu SH,et al.SC-2001 overcomes STAT3-mediated sorafenib resistance through RFX-1/SHP-1 activation in hepatocellular carcinoma[J].Neoplasia,2014,16(7):595-605.
16.Kim DJ,Tremblay ML,Digiovanni J.Protein tyrosine phosphatases,TC-PTP,SHP1,and SHP2,cooperate in rapid dephosphorylation of Stat3 in keratinocytes following UVB irradiation[J].PLoS One,2010,5(4):e10290.
17.Okada S.Conditional ablation of stat3/socs3 discloses the dual role for reactive astrocytes after spinal cord injury[J].Nat Med,2006,12(7):829.
18.杨柳,陈蓓蕾,于海龙,等.JAK2/STAT3信号通路与脑缺血-再灌注损伤相关性的研究进展[J].东南大学学报:医学版,2018,37(1):169-173.YANG Liu,CHEN Beilei,YU Hailong,et al.Research progress of JAK2-STAT3 signal pathway and cerebra ischemia-reperfusion injury[J].Journal of Southeast University.Medical Edition,2018,37(1):169-173.
19.Brooks AJ,Dai W,O’Mara ML,et al.Mechanism of activation of protein kinase JAK2 by the growth hormone receptor[J].Science,2014,344(6185):1249783.
20.Aggarwal BB,Kunnumakkara AB,Harikumarmr KB,et al.Sigal transducer and activator of transcription-3,inflammation,and cancer:how intimate is the relationship[J].Ann N Y Acad Sci,2009,1171:59-76.
21.Gri?th LG,Naughton G.Tissue engineering-current challenges and expanding opportunities[J].Science,2002,295(5557):1009-1014.
22.Nomi M,Atala A,Coppi PD,et al.Principals of neovascularization for tissue engineering[J].Mol Aspects Med,2002,23(6):463-483.
23.Anagnostou A,Liu Z,Steiner M,et al.Erythropoietin receptor mRNAexpression in human endothelial cells[J].Proc Natl Acad Sci U S A,1994,91(9):3974-3978.
24.Nak ano M,Satoh K,Fukumoto Y,et al.Impor tant role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice[J].Circ Res,2007,100(5):662-669.
25.Ribatti D,Presta M,Vacca A,et al.Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo[J].Blood,1999,93(8):2627-2636.
26.Lloyd-Jones D,Adams RJ,Brown TM,et al.Executive summary:heart disease and stroke statistics-2010 update:a report from the American Heart Association[J].Circulation,2010,121(7):948-954.
27.Ch en YC,Wu J,Yang,ST,e t a l.St ro ke,ang i o gen es i s an d phytochemicals[J].Front Biosci(Schol Ed),2012,4:599-610.
28.Zhang J,Chopp M.Cell-based therapy for ischemic stroke[J].Expert Opin Biol Ther,2013,13(9):1229-1240.
29.Juul S.Erythropoietin in the central nervous system,and its use to prevent hypoxic-ischemic brain damage[J].Acta Paediatr Suppl,2002,91(438):36-42.
30.Sola A,Rogido M,Lee BH,et al.Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats[J].Pediatr Res,2005,57(4):481-487.
31.Raible DJ,Frey LC,Brooks-Kayal AR.Effects of JAK2-STAT3 signaling after cerebral insults[J].JAKSTAT,2014,3:e29510.
32.Dong W,Xian Y,Yuan W,et al.Catalpol stimulates VEGF production via the JAK2-STAT3 pathway to improve angiogenesis in rats’stroke model[J].J Ethnopharmacol,2016,191:169-179.
33.Zhao J,Li G,Zhang Y,et al.The potential role of JAK2-STAT3 pathway on the anti-apoptotic effect of recombinant human erythropoietin(rhEPO)after experimental traumatic brain injury of rats[J].Cytokine,2011,56(2):343-350.
34.Liu J,Naasimhan P,Yu F,et al.Neuroprotection by hy pox ic preconditioning involves oxidative stress-mediated expression of hypoxia-inducible factor and erythropoietin[J].Stroke,2005,36(6):1264-1269.
35.Li L,Li H,Li M.Curcumin protects against cerebral ischemiareperfusion injury by activating JAK2-STAT3 signaling pathway in rats[J].Int J Clin Exp Med,2015,8(9):14985.
36.Xuan YT,Guo Y,Han H,et al.An essential role of the JAK-STATpathway in ischemic preconditioning[J].Proc Natl Acad Sci U S A,2001,98(16):9050-9055.
37.Xie XJ,Fan DM,Xi K,et al.Suppression of microRNA-135b-5p protects against myocardial ischemia/reperfusion injury by activating JAK2-STAT3 signaling pathway in mice during sevoflurane anesthesia[J].Biosci Rep,2017,37(3):186-196.
38.Zhao ZQ,Corvera JS,Halkos ME,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion:comparison with ischemic preconditioning[J].Am J Physiol Heart Circ Physiol,2003,285(2):H579-H588.
39.夏大川,田轶魁,吴志浩,等.JAK2-STAT3通路介导缺血后处理心肌保护作用的初步研究[J].天津医药,2010,38(1):43-45.XIA Dachuan,TIAN Yikui,WU Zhihao,et al.Role of the JAK2-STAT3 pathway mediates the cardioprotection of ischemic postconditioning[J].Tianjin Medical Journal,2010,38(1):43-45.
40.Negoro S,Kunisada K,Fujio Y,et al.Activation of signal transducer and activator of transcription 3 protects cardiomyocytes from hy pox ia/reoxygenation-induced ox idative stress through the upregulation of manganese superoxide dismutase[J].Circulation,2001,104(9):979-981.
41.Kalka C,Masuda H,Takahashi T,et al.Vascular endothelial growth factor(165)gene transfer augments circulating endothelial progenitor cells in human subjects[J].Circ Res,2000,86(12):1198-1202.
42.Arras M,Ito WD,Scholz D,et al.Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb[J].J Clin Invest,1998,101(1):40-50.
43.黄伟彬,吕磊,张岚.JAK/STAT信号通路在动脉粥样硬化中的作用[J].上海交通大学学报:医学版,2013,33(4):506-509.HUANG Weibin,LüLei,ZHANG Lan.Effect of JAK/STAT pathway in atherosclerosis[J].Journal of Shanghai Jiao Tong University.Medical Science,2013,33(4):506-509.
44.Neeli I,Liu Z,Dronadula N,et al.An essential role of the Jak-2/STAT-3/cytosolic phospholipase A(2)axis in platelet-derived growth factor BB-induced vascular smooth muscle cell motility[J].J Biol Chem,2004,279(44):46122-46128.
45.Zhang C,Zhao YX,Zhang YH,et al.Angiotensin-converting enzyme2 attenuates atherosclerotic lesions by targeting vascular cells[J].Proc Natl Acad Sci U S A,2010,107(36):15886-15891.
46.Jay DB,Papaharalambus CA,Seidel-Rogol B,et al.Nox5 mediates PDGF-induced proliferation in human aortic smooth muscle cells[J].Free Radic Biol Med,2008,45(3):329-335.
47.朱彬蔚,卞蓉蓉,陈冬平,等.HIPK2基因对缺氧复氧诱导的NRK-52E肾小管上皮细胞活力和凋亡及JAK2/STAT3信号通路的影响[J].中国病理生理杂志,2018,34(6):1075-1080.ZHU Binwei,BIAN Rongrong,CHEN Dongping,et al.Effect of HIPK2 gene on viability,apoptosis and JAK2/STAT3 signaling pathway in NRK-52E renal tubular epithelial cells induced by hypoxia and reoxygenation[J].Chinese Journal of Pathophysiology,2018,34(6):1075-1080.
48.Fan Y,Wang N,Chuang P,et al.Role of HIPK2 in kidney fibrosis[J].Kidney Int Suppl(2011),2014,4(1):97-101.
49.吕娟,曹兰秀.当归黄芪汤对糖尿病大鼠肾组织JAK2STAT3信号通路的影响[J].中国药业,2018,27(15):9-11.LüJuan,CAO Lanxiu.Effect of Danggui Huangqi Decoction on JAK2-STAT3 signaling pathway in renal tissue of diabetic rats[J].China Pharmaceuticals,2018,27(15):9-11.
50.严栋梁,邵伟斌,葛创,等.川芎嗪对刀豆蛋白A诱导的小鼠肝纤维化JAK2/STAT3信号通路的影响[J].肝脏,2018,23(3):255-259.YAN Dongliang,SHAO Weibin,GE Chuang,et al.Effect of tetramethyl pyrazine on JAK2-STAT3 signaling pathway induced by concanavalin Ain liver fibrosis in rats[J].Chinese Hepatology,2018,23(3):255-259.