許文燮

胃腸動(dòng)力及其相關(guān)疾病

許文燮 教授,，醫(yī)學(xué)博士,、現(xiàn)任上海交通大學(xué)醫(yī)學(xué)院解剖與生理學(xué)系教授,、基礎(chǔ)醫(yī)學(xué)院課題組長(zhǎng)（PI）、教學(xué)團(tuán)隊(duì)首席教師,、博士生導(dǎo)師，兼任中國(guó)生理學(xué)會(huì)理事和消化與營(yíng)養(yǎng)專業(yè)委員會(huì)、內(nèi)分泌與代謝專業(yè)委員會(huì)委員,、中國(guó)病理生理學(xué)會(huì)消化專業(yè)委員會(huì)委員、上海生理科學(xué)會(huì)監(jiān)事,、《華人消化病學(xué)雜志》編委,。1997年9月畢業(yè)于韓國(guó)國(guó)立首爾大學(xué)醫(yī)學(xué)院生理系研究生，獲博士學(xué)位,；2000年3月～2001年3月在韓國(guó)國(guó)立全北大學(xué)醫(yī)學(xué)院生理學(xué)教研室從事博士后工作,；2006年、2016年2次到美國(guó)內(nèi)華達(dá)大學(xué)生理系從事訪問學(xué)者工作,；2008年獲教育部留學(xué)基金資助到法國(guó)巴黎11大藥物研究中心從事訪問學(xué)者工作,。

長(zhǎng)期從事消化道平滑肌動(dòng)力及其動(dòng)力障礙的機(jī)制研究工作。到目前,，作為項(xiàng)目負(fù)責(zé)人完成或承擔(dān)國(guó)家自然科學(xué)基金項(xiàng)目8項(xiàng)和教育部項(xiàng)目2項(xiàng),，作為項(xiàng)目組主要成員參加了2項(xiàng)國(guó)家自然科學(xué)基金重點(diǎn)項(xiàng)目。在“Cell Physiol Biochem”,，“Neurogastroenterol Motil”,，“Mol Cell Endocrinol”，“Eur J Pharmacol”等學(xué)術(shù)刊物發(fā)表論文100多篇,，其中SCI論文共50余篇,。作為主編、副主編和編者參加編寫統(tǒng)編教材和專著12部,。2017年獲得寶鋼教育優(yōu)秀教師獎(jiǎng),、上海交通大學(xué)優(yōu)秀教師、獲得基礎(chǔ)醫(yī)學(xué)院杰出員工獎(jiǎng),；2016年上海交通大學(xué)醫(yī)學(xué)院優(yōu)秀共產(chǎn)黨員/師德標(biāo)兵,；2004、2008年分別以第一完成人獲得省部級(jí)科技進(jìn)步二等獎(jiǎng)2項(xiàng),。2002年被評(píng)為教育部?jī)?yōu)秀骨干教師,。

研究方向與進(jìn)展

本課題的主要研究方向是消化道平滑肌動(dòng)力及其動(dòng)力障礙的機(jī)制研究，尤其是腸神經(jīng)調(diào)控胃腸動(dòng)力的機(jī)制、間質(zhì)細(xì)胞Cajal間質(zhì)細(xì)胞（ICC）以及PDGFR               調(diào)控胃腸動(dòng)力的機(jī)理,。闡明胃腸平滑肌運(yùn)動(dòng)調(diào)控中腸神經(jīng)-ICC,、PDGFR               -平滑肌網(wǎng)絡(luò)在胃腸動(dòng)力調(diào)控中的生理學(xué)機(jī)制及其意義，最終解析在胃腸動(dòng)力障礙性疾病發(fā)病,、發(fā)展過程中的重要作用,。經(jīng)過多年研究以下幾個(gè)方面研究進(jìn)展和研究成果：

1.胃腸運(yùn)動(dòng)調(diào)控中腸神經(jīng)的作用非常重要，其中兩種間質(zhì)細(xì)胞不僅起動(dòng)自發(fā)節(jié)律性運(yùn)動(dòng)還介導(dǎo)腸神經(jīng)調(diào)控平滑肌運(yùn)動(dòng)的過程,。所以損傷間質(zhì)細(xì)胞可以引起各種胃腸動(dòng)力障礙性疾病,，例如糖尿病引起胃輕癱、糖尿病引起結(jié)腸傳輸性便秘以及炎癥性腸病的動(dòng)力障礙例如便秘或腹瀉等,。

2.在結(jié)腸傳輸運(yùn)動(dòng)調(diào)控中腸神經(jīng),、兩種間質(zhì)細(xì)胞（ICC和PDGFR               ）以及平滑肌細(xì)胞（smooth muscle）通過縫隙連接形成SIP合胞體,形成骨骼肌類似的運(yùn)動(dòng)單位（motor unit），在結(jié)腸運(yùn)動(dòng)和傳輸運(yùn)動(dòng)調(diào)控中起著重要作用,。所以,，SIP合胞體是結(jié)腸運(yùn)動(dòng)和傳輸機(jī)制研究的靶點(diǎn)，也是結(jié)腸傳輸功能障礙性疾病機(jī)制研究的重要靶點(diǎn)

3.我們發(fā)現(xiàn)胃腸黏膜腸嗜鉻細(xì)胞合成分泌利尿鈉肽（natriuretic peptide, NPs）參與胃平滑肌運(yùn)動(dòng)調(diào)控,也參與糖尿病胃輕癱發(fā)生過程中起著重要的作用,。

4.胃平滑肌細(xì)胞內(nèi)兩種氣體信號(hào)分子H₂S和NO共存,，這兩種氣體信號(hào)分子對(duì)胃平滑肌張力起相反的作用，即H₂S增加平滑肌張力起興奮作用,，而NO抑制平滑肌張力起抑制作用,。這兩種氣體分子在正常生理?xiàng)l件下保持動(dòng)態(tài)平衡共同維持胃平滑肌張力。

5.牽張應(yīng)變是胃腸重要的生理性刺激,。我們闡明了牽張應(yīng)變調(diào)控ICC起搏電流機(jī)制并腸梗阻引起的平滑肌細(xì)胞肥厚,、肥大導(dǎo)致平滑肌細(xì)胞K_V增多伴隨電流密度降低的現(xiàn)象與K_V通道蛋白磷酸化改變有關(guān)，梗阻平滑肌電流密度降低與膜電位去極化有關(guān),。

科研項(xiàng)目

代表性論文：

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.

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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.

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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.

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    團(tuán)隊(duì)介紹：

        團(tuán)隊(duì)成員共3人,，其中教授1人,、副教授1人、助理研究員1人,。目前團(tuán)隊(duì)的成員均承擔(dān)過國(guó)家和上海市的科研課題，順利完成了研究任務(wù)，在研的研究項(xiàng)目順利進(jìn)展,。他們已經(jīng)具備了獨(dú)立進(jìn)行科學(xué)研究能力并且可以配合PI指導(dǎo)研究生研究生,，同時(shí)較強(qiáng)的管理實(shí)驗(yàn)室能力。他們?cè)诮虒W(xué)中各自參與教學(xué)團(tuán)隊(duì),，成為教學(xué)骨干,，可以獨(dú)立負(fù)責(zé)課程建設(shè)項(xiàng)目，曾在學(xué)院和全國(guó)教學(xué)比賽中獲得獎(jiǎng)項(xiàng),。