Newsletter No. 475

8 475 • 4.4.2016 ’ 口談實錄 Viva Voce 本刊由香港中文大學資訊處出版，每月出版兩期。截稿日期及稿例載於 www.iso.cuhk.edu.hk/chinese/newsletter/ 。 The CUHK Newsletter is published by the Information Services Office, CUHK, on a fortnightly basis. Submission guidelines and deadlines can be found at www.iso.cuhk.edu.hk/english/newsletter/ . 藍輝耀教授 Prof. Lan Hui-yao • 卓敏生物醫學講座教授 • 以「慢性腎臟病進展的機制及臨床防治研究」 獲頒2015年中華醫學科技獎一等獎 • Choh-Ming Li Professor of Biomedical Sciences • Awarded First Prize in Chinese Medical Science and Technology Award for his project entitled ‘Research into the Mechanism and Control of Clinical Progression of Chronic Kidney Diseases’ 請簡介你得獎的研究。 當人體組織纖維化，即有傷疤，會令組織結構受損，逐步喪失 功能，繼而器官衰竭，如心、肺、肝及腎衰竭。我經多年研究， 發現TGF-β1/Smad信號傳遞在形成傷疤組織起了關鍵作 用。是次研究是與南方醫科大學、東南大學、山東大學、中國 科學院昆明植物研究所及復旦大學合作，深入而系統化找出 導致腎纖維化的機制，期能對症下藥。 研究確定在TGF-β1/Smad信號傳遞中一個名為Smad3蛋白分 子過多，是引致纖維化的原因，而本用以抵抗纖維化的Smad7 蛋白分子則丟失了。套用中醫理論來說，是陽（Smad3）盛 陰（Smad7）衰所致。我們又發現存於常見柑橘類果皮的柚 皮素能有效抑制Smad3，常用的陳皮就含有柚皮素；而積雪 草酸則可刺激Smad7的產生，中醫就以積雪草來活血消腫。 把兩者結合入藥，可望成為治療慢性腎病的新法。 怎樣想到應用中醫理論來治療？ 根據我從事病理學研究多年的心得，「失衡」是致病主因。 中醫理論基礎是強調陰陽平衡，五臟六腑和諧協調，最切合 用於治療「失衡」上。 相關研究去年也獲國家教育部頒發高等學校科學研究優 秀成果獎，再次獲獎，有甚麼感想？ 研究既無止境，也無捷徑。愈是研究，愈發現更多問題。獲獎 不過是代表研究工作一個階段的總結，而非終點，反倒是一 股動力，鞭策我開展下一階段的研究。去年獲得的優秀成果 獎，是校內團隊的研究。今年獲中華醫學科技獎，則結合了中 大和內地多間大學研究團隊的努力。 那麼下一步的工作是甚麼？ 我們計劃把研究成果轉為臨床應用，研發抗纖維化的藥物和 療法，主力研究柚皮素和積雪草複方。研究過程中，我們亦發 現了TGF-β1/Smad信號傳遞的失衡是導致喪失抗腫瘤能力 的主因，揭示一個新研究方向─TGF-β1/Smad信號傳遞在 腫瘤微環境中的作用和機制。 甚麼原因促使你專注腎臟疾病的研究？ 我在廣州中山醫學院畢業之時，腎臟科在內地還未發展為專 科，我應邀參與建立和發展腎臟科，由此從事腎臟病病理研 究。再說，腎病是威脅人類健康的主要疾病之一，晚期患者更 需要血液透析（俗稱洗腎）或腎移植以延續生命，不容輕視。 唸醫科的你，為何不行醫而以研究和教育為志業？ 我在臨床實踐中，發現慢性疾病總是帶有傷疤組織，可是，這 些傷疤如何形成，卻仍然是一個謎。是以，我轉戰研究工作， 矢志要破解箇中奧秘，以期研發有效的療法。畢業後便開始 教書，深深了解到通過教學，才能把想法和理念傳承下去，發 揚光大。故我定下「重研重教」為人生宗旨。我的研究團隊成 員以研究生為主，從澳洲、美國至香港，二十多年來，已培育了 八十多位博士生及博士後研究生，當中不少已在世界各地的 專科領域中擔任領導者角色。過往的研究取得佳績，都是要 歸功他們。看到他們的卓越成長，令我倍感欣慰，也是人生的 最大樂趣。 Please briefly introduce your award-winning research project. When fibrosis occurs in human tissues, the scarring that ensues can damage the tissues, causing them to gradually lose their functions. This is followed by organ failure, such as that of the heart, lungs, liver and kidneys. Through my years of research, I have found that TGF- β 1/Smad signalling pathway plays a critical role in tissues scar formation. This research project marks our collaboration with Southern Medical University, Southeast University, Shandong University, Kunming Institute of Botany of the Chinese Academy of Sciences and Fudan University. Together, we conducted an in-depth and systematic study to find out the mechanism of renal fibrosis, with the aim of finding the right treatment. Our research discovered that the cause of fibrosis is due to excessive Smad3 molecules in the TGF- β 1/Smad signalling pathway, while Smad7 molecules, a protector from fibrosis, are missing. From a traditional Chinese medicine (TCM) perspective, the cause can be attributed to an imbalance of a strong yang (Smad3) and a weak yin (Smad7). We also found that Smad3 can be inhibited by naringenin, commonly found in citrus peel. Asiatic acid, used by TCM practitioners to facilitate blood circulation and reduce inflammation, can stimulate Smad7 production. Combining these two in medicine can be expected to offer a new treatment for chronic renal disease. What made you think of applying TCM theory for treatment? Based on my pathological research over many years, ‘ imbalance ’ is the primary cause of disease. TCM theory emphasizes a yin-yang balance. Treatment for ‘ imbalance ’ can be achieved through harmonious coordination of the body’s vital organs. This research project received the Higher Education Outstanding Scientific Research Output Awards from the Ministry of Education last year. What does winning another award mean to you? There is no end or shortcut in research. The deeper you probe, the more issues you will uncover. Winning an award doesn’t signify an end in our work but is a driving force impelling us to embark on the next stage of research. The award we received last year was a recognition of the work of our CUHK research team, whereas the award conferred to the project this year honours the combined hard work of CUHK and several universities on the mainland. What will you be working on next? We plan to use our research in clinical practices to develop anti-fibrosis medicine and treatments, with a focus on formulating naringenin and Asiatic acid compound prescriptions. In the process, we discovered that TGF- β 1/ Smad signalling imbalance leads to the loss of the body’s tumour-fighting ability. This pointed to a new research direction—the function and mechanism of TGF β 1/Smad in the tumour microenvironment. What made you specialize in renal disease research? At the time when I graduated from the Zhongshan School of Medicine in Guangzhou, nephrology had not yet developed into a medical speciality on the mainland. Upon invitation, I became involved in setting up and developing the nephrology department and from then on, started to engage in nephrology research. Furthermore, renal disease is one of the major threats to human health. End-stage patients are required to undergo peritoneal dialysis (popularly known as cleansing the abdomen) or kidney transplant to prolong their lives. So this problem merits serious medical attention. As a medical graduate, why did you not choose to practise medicine but take up research and education as your lifelong career? In my clinical practice, I found that chronic diseases are invariably linked to scarred tissues, but how the scars are formed still remains a mystery. Subsequently, I switched to research work to unravel the causes, hoping to produce effective treatments from R&D work. After graduation, I started teaching and it made me realize that through teaching, I could pass on my insights and vision and magnify their impact. This is why I have incorporated a dual emphasis on research and teaching into my lifelong goal. Over the past 20 years, I have groomed over 80 PhD students and post-doctoral fellows in Australia, the US and Hong Kong. Many of them now hold leadership roles in specialist medical disciplines in various parts of the world. They must also be credited for the outstanding research work we produced together in the past. It is gratifying to witness their professional growth and excellent accomplishments and this is the greatest joy of my life. Photo by ISO staff