代小艳-广州医科大学药学院

代小艳，女，教授。2009年进入北京大学医学部，师从著名心血管专家王宪教授攻读博士学位。2012年博士毕业后前往美国奥克拉荷马大学医学部和佐治亚州立大学分子和转化医学中心，跟随美国医学科学院院士、国际心血管及代谢疾病领域知名专家邹明辉教授从事博士后研究。长期致力于从巨噬细胞及炎症因子角度研究血管性疾病的病理机制，包括①动脉粥样硬化（Atherosclerosis, As）、②血管钙化、③胰岛素抵抗、④脓毒症的免疫及炎性机制。自2012年以来，申请者以第一作者或共同作者在Circ Res、Diabetes、Kidney Int、Nat Med、Circulation等国际一流杂志发表论文15篇。其中，第一作者5篇，并列第一作者2篇。经美国Web of Science数据库检索，申请者发表的15篇论文被引总次数为237，他引次数为231。主持完成美国心脏协会（American Heart Association）课题一项。

联系邮箱：xdai@gzhmu.edu.cn

研究方向：心血管药理

主要科研项目及成果：

申请者长期致力于从巨噬细胞及炎症因子角度研究血管性疾病的病理机制，包括①动脉粥样硬化（Atherosclerosis, As）、②血管钙化、③胰岛素抵抗、④脓毒症的免疫及炎性机制，成果如下：1）揭示腺苷酸活化蛋白激酶（AMPK）具有抑制As易损斑块形成的新作用。探索了AMPK作为治疗As潜在靶点的新可能性；提出了AMPK是As斑块稳定性保护因素的新观点；主持完成美国心脏协会（American Heart Association, AHA）课题-- Regulation of CHOP by AMPK（14POST18690055）；以第一作者发表论文1篇（Circ Res），后即被Circ Res以及Cell子刊Trends in Endocrinology & Metabolism正面引用。2）阐明内源性活性多肽中介素、亮氨酸抑制As形成的作用及机制。此研究丰富了中介素和亮氨酸对心血管的保护作用。证明中介素通过CRLR-cAMP-PKA信号通路降低CD36和SR-A表达，减少巨噬细胞源性泡沫细胞形成，抑制As发生发展。亮氨酸促进ABCG5/ABCG8介导的胆固醇从肝脏流出，抑制全身性炎症，改善ApoE^-/-小鼠的血浆脂质谱，从而减轻As病变。以第一作者或并列第一作者发表学术论文3篇（Cardiovasc Res、J Mol Cell Cardiol和Acta Pharmacol Sin）。3）发现自噬对高磷诱导的血管钙化具有保护作用。确立自噬是高磷酸盐诱导的血管钙化中的新适应性保护机制；以第一作者发表论文1篇（Kidney Int），并获述评（Kidney Int）（见附件6）。4）确立巨噬细胞Neuropilin 1（Nrp1）是对抗胰岛素抵抗和脓毒症的新分子。此研究发现巨噬细胞Nrp1在胰岛素抵抗中的保护性作用（第一作者Diabetes）和在脓毒症中的新型抗炎作用（第一作者FASEB J），为治疗胰岛素抵抗和脓毒症提供了新的潜在靶点。

所获荣誉和奖励：

1. 代小艳 (1/1)，第十一届海峡两岸心血管科学研讨会青年优秀论文报告，二等奖，2017。奖励

2. 代小艳(1/1)，北京大学医学部通用电气教育奖项，2011。奖励

3. 代小艳(1/1)，北京大学医学部二等奖学金，2011，2010，2009。奖励

4. 代小艳(1/1)，湖南省优秀毕业论文，2009。奖励

5. 代小艳(1/1)，第九次全国动脉硬化性疾病学术会议青年优秀论文评选，一等奖，2007。奖励

6. 代小艳，唐志晗，动脉粥样硬化研究的形态学方法和技术，科学出版社，1410千字，2017。专著

主要论文及著作：

1.Dai X, Okon I, Liu Z, Bedarida T, Wang Q, Ramprasath T, Zhang M, Song P, Zou MH ^(*). Ablation of Neuropilin 1 in Myeloid Cells Exacerbates High-Fat Diet-Induced Insulin Resistance Through Nlrp3 Inflammasome In Vivo. Diabetes. 2017 Sep; 66(9):2424-2435.

2.Dai X, Okon I, Liu Z, Wu Y, Zhu H, Song P, Zou MH^(*). A novel role for myeloid cell-specific neuropilin 1 in mitigating sepsis. FASEB J. 2017 Jul; 31(7):2881-2892.

3.Dai X, Ding Y, Liu Z, Zhang W, Zou MH^(*). Phosphorylation of CHOP (C/EBP Homologous Protein) by the AMP-Activated Protein Kinase Alpha 1 in Macrophages Promotes CHOP Degradation and Reduces Injury-Induced Neointimal Disruption In Vivo. Circ Res. 2016 Oct 28; 119(10):1089-1100.

4.Dai XY, Cai Y, Sun W, Ding Y, Wang W, Kong W, Tang C, Zhu Y, Xu MJ ^(*), Wang X. Intermedin inhibits macrophage foam-cell formation via tristetraprolin-mediated decay of CD36 mRNA. Cardiovasc Res. 2014 Feb 1; 101(2):297-305.

5.Dai XY^(#), Zhao MM^(#), Cai Y, Guan QC, Zhao Y, Guan Y, Kong W, Zhu WG, Xu MJ ^(*), Wang X. Phosphate-induced autophagy counteracts vascular calcification by reducing matrix vesicle release. Kidney Int. 2013 Jun;83(6):1042-51.

6.Dai XY, Cai Y, Mao DD, Qi YF, Tang C, Xu Q, Zhu Y, Xu MJ ^(*), Wang X ^(*). Increased stability of phosphatase and tensin homolog by intermedin leading to scavenger receptor A inhibition of macrophages reduces atherosclerosis in apolipoprotein E-deficient mice. J Mol Cell Cardiol. 2012 Oct; 53(4):509-20.

7.Zhao Y^(#), Dai XY ^(#), Zhou Z, Zhao GX, Wang X, Xu MJ ^(*). Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice. Acta Pharmacol Sin. 2016 Feb; 37(2):196-203.

8.Liu Z, Zhu H, Dai X, Wang C, Ding Y, Song P, Zou MH ^(*). Macrophage Liver Kinase B1 Inhibits Foam Cell Formation and Atherosclerosis. Circ Res. 2017 Oct 13; 121(9):1047-1057.

9.Wang Q, Wu S, Zhu H, Ding Y, Dai X, Ouyang C, Han YM, Xie Z ^(*), Zou MH^(*). Deletion of PRKAA triggers mitochondrial fission by inhibiting the autophagy-dependent degradation of DNM1L. Autophagy. 2017 Jan; 13:1-19.

10.Zhu H, Zhang M, Liu Z, Xing J, Moriasi C, Dai X, Zou MH^(*). AMP-Activated Protein Kinase α1 in Macrophages Promotes Collateral Remodeling and Arteriogenesis in Mice In Vivo. Arterioscler Thromb Vasc Biol. 2016 Sep; 36(9):1868-78.

11.Liu Z, Dai X, Zhu H, Zhang M, Zou MH ^(*). Lipopolysaccharides Promote S-Nitrosylation and Proteasomal Degradation of Liver Kinase B1 (LKB1) in Macrophages in Vivo. J Biol Chem. 2015 Jul 31; 290(31):19011-7.

12.Wu Y, Song P, Zhang W, Liu J, Dai X, Liu Z, Lu Q, Ouyang C, Xie Z, Zhao Z, Zhuo X, Viollet B, Foretz M, Wu J, Yuan Z^(*), Zou MH^(*). Activation of AMPKα2 in adipocytes is essential for nicotine-induced insulin resistance in vivo. Nat Med. 2015 Apr; 21(4):373-82.

13.Zhang W, Wang Q, Wu Y, Moriasi C, Liu Z, Dai X, Wang Q, Liu W, Yuan ZY, Zou MH^(*). Endothelial cell-specific liver kinase B1 deletion causes endothelial dysfunction and hypertension in mice in vivo. Circulation. 2014 Apr 1; 129(13):1428-39.

14.Song P, Zhou Y, Coughlan KA, Dai X, Xu H, Viollet B, Zou MH^(*). Adenosine monophosphate-activated protein kinase-α2 deficiency promotes vascular smooth muscle cell migration via S-phase kinase-associated protein 2 upregulation and E-cadherin downregulation. Arterioscler Thromb Vasc Biol. 2013 Dec; 33(12):2800-9.

15.Zhao G ^(#), Xu MJ ^(#), Zhao MM, Dai XY, Kong W, Wilson GM, Guan Y, Wang CY^(*), Wang X^(*). Activation of nuclear factor-kappa B accelerates vascular calcification by inhibiting ankylosis protein homolog expression. Kidney Int. 2012 Jul; 82(1):34-44.

16.Dai XY, Ou X, Hao XR, Cao DL, Tang YL, Hu YW, Li XX, Tang CK^*. The effect of T0901317 on ATP-binding cassette transporter A1 and Niemann-Pick typeC1 in apoE-/- mice. J Cardiovasc Pharmacol. 2008 May; 51(5):467-75.

17.Ou X^#, Dai X^#, Long Z, Tang Y, Cao D, Hao X, Hu Y, Li X, Tang C^*. Liver X receptor agonist T0901317 reduces atherosclerotic lesions in apoE-/- mice by up-regulating NPC1 expression. Sci China C Life Sci. 2008 May; 51(5):418-29.

18.Dai X, Ou X, Hao X, Cao D, Tang Y, Hu Y, Li X, Tang C^(*). Synthetic liver X receptor agonist T0901317 inhibits semicarbazide-sensitive amine oxidase gene expression and activity in apolipoprotein E knockout mice. Acta Biochim Biophys Sin (Shanghai). 2008 Mar; 40(3):261-8.

19.Dai X, Ou X, Hao X, Cao D, Tang Y, Hu Y, Li X, Tang C^(*). Effect of T0901317 on hepatic proinflammatory gene expression in apoE-/- mice fed a high-fat/high-cholesterol diet. Inflammation. 2007 Aug;30(3-4):105-17.

20.Dai X, Okon I, Zou MH. Myeloid cell neuropilin 1 ameliorates high-fat diet-induced insulin resistance via suppression of Nlrp3 inflammasome. Macrophage (Houst). 2017;4. pii: e1594.