许文燮

胃肠动力及其相关疾病

许文燮 教授，医学博士、现任欧洲杯竞猜平台解剖与生理学系教授、基础欧洲杯竞猜平台课题组长（PI）、教学团队首席教师、博士生导师，兼任中国生理学会理事和消化与营养专业委员会、内分泌与代谢专业委员会委员、中国病理生理学会消化专业委员会委员、上海生理科学会监事、《华人消化病学杂志》编委。1997年9月毕业于韩国国立首尔大学欧洲杯竞猜平台生理系研究生，获博士学位；2000年3月～2001年3月在韩国国立全北大学欧洲杯竞猜平台生理学教研室从事博士后工作；2006年、2016年2次到美国内华达大学生理系从事访问学者工作；2008年获教育部留学基金资助到法国巴黎11大药物研究中心从事访问学者工作。

长期从事消化道平滑肌动力及其动力障碍的机制研究工作。到目前，作为项目负责人完成或承担国家自然科学基金项目8项和教育部项目2项，作为项目组主要成员参加了2项国家自然科学基金重点项目。在“Cell Physiol Biochem”，“Neurogastroenterol Motil”，“Mol Cell Endocrinol”，“Eur J Pharmacol”等学术刊物发表论文100多篇，其中SCI论文共50余篇。作为主编、副主编和编者参加编写统编教材和专著12部。2017年获得宝钢教育优秀教师奖、欧洲杯竞猜平台优秀教师、获得基础欧洲杯竞猜平台杰出员工奖；2016年欧洲杯竞猜平台优秀共产党员/师德标兵；2004、2008年分别以第一完成人获得省部级科技进步二等奖2项。2002年被评为教育部优秀骨干教师。

研究方向与进展

本课题的主要研究方向是消化道平滑肌动力及其动力障碍的机制研究，尤其是肠神经调控胃肠动力的机制、间质细胞Cajal间质细胞（ICC）以及PDGFR               调控胃肠动力的机理。阐明胃肠平滑肌运动调控中肠神经-ICC、PDGFR               -平滑肌网络在胃肠动力调控中的生理学机制及其意义，最终解析在胃肠动力障碍性疾病发病、发展过程中的重要作用。经过多年研究以下几个方面研究进展和研究成果：

1.胃肠运动调控中肠神经的作用非常重要，其中两种间质细胞不仅起动自发节律性运动还介导肠神经调控平滑肌运动的过程。所以损伤间质细胞可以引起各种胃肠动力障碍性疾病，例如糖尿病引起胃轻瘫、糖尿病引起结肠传输性便秘以及炎症性肠病的动力障碍例如便秘或腹泻等。

2.在结肠传输运动调控中肠神经、两种间质细胞（ICC和PDGFR               ）以及平滑肌细胞（smooth muscle）通过缝隙连接形成SIP合胞体,形成骨骼肌类似的运动单位（motor unit），在结肠运动和传输运动调控中起着重要作用。所以，SIP合胞体是结肠运动和传输机制研究的靶点，也是结肠传输功能障碍性疾病机制研究的重要靶点

3.我们发现胃肠黏膜肠嗜铬细胞合成分泌利尿钠肽（natriuretic peptide, NPs）参与胃平滑肌运动调控,也参与糖尿病胃轻瘫发生过程中起着重要的作用。

4.胃平滑肌细胞内两种气体信号分子H₂S和NO共存，这两种气体信号分子对胃平滑肌张力起相反的作用，即H₂S增加平滑肌张力起兴奋作用，而NO抑制平滑肌张力起抑制作用。这两种气体分子在正常生理条件下保持动态平衡共同维持胃平滑肌张力。

5.牵张应变是胃肠重要的生理性刺激。我们阐明了牵张应变调控ICC起搏电流机制并肠梗阻引起的平滑肌细胞肥厚、肥大导致平滑肌细胞K_V增多伴随电流密度降低的现象与K_V通道蛋白磷酸化改变有关，梗阻平滑肌电流密度降低与膜电位去极化有关。

科研项目

代表性论文：

1. Chun-Mei Zhang, Xu Huang, Hong-Li Lub, Xiang-Min Meng, Ni-Na Song, Lu Chenb, Young-Chul Kim, Jie Chen, Wen-Xie Xu* Diabetes-induced damage of gastric nitric oxide neurons mediated by P2X7R in diabetic mice. Eur J Pharmacol, 2019, 851: 151–160.

2. Chen Lu, Hongli Lu, Xu Huang, Shaohua Liu, Jingyu Zang, Yujia Li,1 Jie Chen, and Wenxie Xu*. Colonic Transit Disorder Mediated by Downregulation of Interstitial Cells of Cajal/Anoctamin-1 in Dextran Sodium Sulfate-induced Colitis Mice. J Neurogastroenterol Motil, 2019, 25: 316-331.

3. Ling TONG, Jun-Ping AO, Hong-Li LU, Xu HUANG, Jing-Yu ZANG, Shao-Hua LIU, Ni-Na SONG, Shi-Qi HUANG, Chen Lu, Jie CHEN, Wen-Xie XU. Tyrosine Kinase Pyk2 is Involved in Colonic Smooth Muscle Contraction via the RhoA/ROCK Pathway. Physiol. Res. 2019, 68: 89-98

4. Chen Lu, Xu Huang, Hong-Li Lu, Shao-Hua Liu, Jing-Yu Zang, Yu-Jia Li, Jie Chen, Wen-Xie Xu. Different distributions of interstitial cells of Cajal and platelet-derived growth factor receptor-α positive cells in colonic smooth muscle cell/interstitial cell of Cajal/plateletderived growth factor receptor-α positive cell syncytium in mice. World J Gastroenterol, 2018, 24: 4989-5004

5. Song NN, Lu HL, Lu C, Tong L, Huang SQ, Huang X，Chen J, Kim YC, Xu WX. Diabetes-induced colonic slow transit mediated by the up-regulation of PDGFRα+ cells/SK3 in streptozotocin-induced diabetic mice. Neurogastroenterol Motil, 2018, DOI: 10.1111/nmo.13326.

6. Lu HL, Zhang CM, Song NN, Lu C, Tong L, Huang X, Kim YC, Chen J, Xu WX. Colonic PDGFRα Overexpression Accompanied Forkhead Transcription Factor FOXO3 Up-Regulation in STZ-Induced Diabetic Mice. Cell Physiol Biochem, 2017, 43:158-171.

7. Mao YL, Shen CL, Zhou T, Ma BT, Tang LY, Wu WT, Zhang HX, Lu HL, Xu WX, Wang ZG. Ablation of Tacr2 in mice leads to gastric emptying disturbance. Neurogastroenterol Motil, 2017, doi: 10.1111/nmo.13117.

8. Meng XM, Huang X, Lu HL, Zhang CM, Kim YC, Chen J, Xu WX. H2 S-induced gastric fundus smooth muscle tension potentiation is mediated by the phosphoinositide 3-kinase/Akt/endothelial nitric oxide synthase pathway. Exp Physiol, 2017, 102: 779-790.

9. Peng Zhang, Yue Han, Hong-Li Lu, Chun-Mei Zhang, Ni-Na Song, Ying-Xin Qi, Wen-Xie Xu, Zong-Lai Jiang. Aortic vascular reactivity to angiotension II is modulated by down-regulation of TRPC in renal hypertensive rats. Int J Clin Exp Pathol, 2016, 9:11003-11013.

10. Song NN, XU WX. Physiological and pathophysiological meanings of gastrointestinal smooth muscle motor unit SIP syncytium. Acta Physiologica Sinica, 2016, 68: 621–627.

11. Hong SH, Kyeong KS, Kim CH, Kim YC, Choi W, Yoo RY, Kim HS, Park YJ,Ji IW, Jeong EH, Kim HS, Xu WX and Lee SJ. Regulation of myometrial contraction by ATP-sensitive potassium (KATP) channel via ctivation of SUR2B and Kir 6.2 in mouse. J Vet Med Sci, 2016,78: 1153–1159.

12. Zhang CM, Huang X, Lu HL, Meng XM, Liu DH, Kim YC, Xu WX. Up-regulation of the Ang II/AT1 receptor may compensate for the loss of gastric antrum ICC via the PI3k/Akt signaling pathway in STZ-induced diabetic mice. Mol Cell Endocrinol, 2016, 423: 77-86.

1. Meng XM, Huang X, Zhang CM, Liu DX, Lu HL, Xu WX. Hydrogen sulfide-induced enhancement of gastric fundus smooth muscle tone is mediated by voltage-dependent potassium and calcium channels in mice. World J Gastroenterol, 2015, 21: 4840-4851.

2. Huang X and Xu WX. Synthesis of H2S in the Gastrointestinal Tract. Gastroenterol Hepatol Res, 2015, 4: 1459-1464.

3. Wang ZY, Huang X, Liu DH, Lu HL, Kim YC, Xu WX. Involvement of Actin Microfilament in Regulation of Pacemaking Activity Increased by Hypotonic Stress in Cultured ICCs of Murine Intestine. Physiol Res, 2015, 64: 397-405.

4. Liu DH，Huang X，Meng XM, Zhang CM, Lu HL, Kim YC, Xu WX. Exogenous H 2 S enhances mice gastric smooth muscle tension through S-sulfhydration of K V 4.3, mediating the inhibition of the voltage-dependent potassium current. Neurogastroenterol Motil, 2014, 26: 1705–1716.

5. Liu DH, Huang X, Guo X, Meng XM, Wu YS, Lu HL, Zhang CM, Kim YC, Xu WX. Voltage Dependent Potassium Channel Remodeling in Murine Intestinal Smooth Muscle Hypertrophy Induced by Partial Obstruction. Plos One, 2014, 9(2): e86109. doi:10.1371.

6. Lu HL, Xu Huang, Yi-Song Wu, Chun-Mei Zhang, Xiang-Min Meng, Dong-Hai Liu, Young-chul Kim, Wen-Xie Xu. Gastric nNOS reduction accompanied by natriuretic peptides signaling pathway upregulation in diabetic mice. World J Gastroenterol, 2014, 20: 4626-4635.

7. Xu Huang, Xiang-Min Meng, Dong-Hai Liu, Yi-Song Wu, Xin Guo, Hong-Li Lu, Xue-Yan Zhuang , Young-chul Kim, Wen-Xie Xu. Different regulatory effects of hydrogen sulfide and nitric oxide on gastric motility in mice. Eur J Pharmacol, 2013, 720: 276-285.

8. Wu YS, Lu HL, Huang X, Liu DH, Meng XM, Guo X, Kim YC, Xu WX*. Diabetes-induced loss of gastric ICC accompanied by up-regulation of natriuretic peptide signaling pathways in STZ-induced diabetic mice. Peptides. 2013, 40: 104-111.

9. Ying-Lan Cai, Qian Sun, Xu Huang, Jing-Zhi Jiang, Mo-Han Zhang, Li-Hua Piao, Zheng Jin, Wen-Xie Xu. cGMP–PDE3–cAMP signal pathway involved in the inhibitory effect of CNP on gastric motility in rat. Regulatory Peptides, 2013, 180: 43–49.

10. Xin Guo, Xu Huang, Yi-song Wu, Dong-hai Liu, Hong-li Lu, Yong-chul Kim, Wen-xie Xu. Down-regulation of hydrogen sulfide biosynthesis accompanies murine interstitial cells of Cajal dysfunction in partial ileal obstruction. Plos One, 2012, 7(11) e48249. doi:10.1371.

11. Lu HL, Wang ZY, Huang X, Han YF, Wu YS, Guo X, Kim YC, Xu WX. Excitatory regulation of angiotensin II on gastric motility and its mechanism in guinea pig. Regul Pept. 2011, 167：170-176.

12. Yan-fei Han, Xu Huang, Xin Guo , Yi-song Wu, Dong-hai Liu , Hong-li Lu, Young-chul Kim , Wen-xie Xu. Evidence that endogenous hydrogen sulfide exerts an excitatory effect on gastric motility in mice. Eur J Pharmacol, 2011, 673: 85–95

13. Wang ZY, Han YR, Huang Xu, Peng Zhao, Lu HL, Guo X, Kim YC, Xu WX. Pacemaking activity is regulated by membrane stretch via the CICR pathway in cultured interstitial cells of Cajal from murine intestine. Biomechanics, 2010, 43：2214–2220.

14. Xu Huang，Wen Xie Xu. The pacemaker functions of visceral interstitial cells of Cajal. Acta Physiol Sin, 2010, 62: 387-397.

15. Huang X, Zhao D, Wang ZY, Zhang ML, Yan ZQ, Han YF, Xu WX, Jiang ZL.The properties of spontaneous transient inward currents of interstitial cells in rabbit portal vein. Eur J Pharmacol. 2010, 643: 63–69

16. Huang X, Zhao D, Wang ZY, Zhang ML, Yan ZQ, Han YF, Lu HL, Xu WX, Jiang ZL. Spontaneous rhythmic inward currents recorded in interstitial cells of rabbit portal vein. Cell Biochem Biophys. 2010，57: 77-85.

17. Wang ZY, Han YF, Huang X, Lu HL, Guo X, Kim YC, Xu WX. Actin microfilament involved in regulation of pacemaking activity in cultured interstitial cells of Cajal from murine intestine. Membr Biol., 2010, 234:217-25.

18. Qiu ZX, Mei B, Wu YS, Huang X, Wang ZY, Han YF, Lu HL, Kim YC, Xu WX. Atrial natriuretic peptide signal pathway upregulated in stomach of streptozotocin-induced diabetic mice. World J Gastroenterol, 2010, 16: 48-55.

19. Zhao P Xu H Wang ZW Qiu ZX Han YF Lu HL Kim YC Xu WX. Dual effect of exogenous hydrogen sulfide on the spontaneous contraction of gastric smooth muscle in guinea-pig. Eu J Pharmacol, 2009. 616: 223–228.

20. Xu HY, Huang X, Yang M, Sun JB, Piao LH, Zhang Y, Gao L, Xu WX. The Effect of C-Type Natriuretic peptide on Delayed Rectifier Potassium Currents in Gastric Antral Circular Myocytes of the Guinea-Pig. Physiol Res. 2008;57:55-62.

     

    团队介绍：

        团队成员共3人，其中教授1人、副教授1人、助理研究员1人。目前团队的成员均承担过国家和上海市的科研课题，顺利完成了研究任务，在研的研究项目顺利进展。他们已经具备了独立进行科学研究能力并且可以配合PI指导研究生研究生，同时较强的管理实验室能力。他们在教学中各自参与教学团队，成为教学骨干，可以独立负责课程建设项目，曾在学院和全国教学比赛中获得奖项。