研究室資料

專長領域

1. 腎臟生理與病理

2. 腸–肝–腎軸整合性生理調控

3. 肥胖與代謝性脂肪肝（MAFLD）

研究主題

本實驗室聚焦於代謝性疾病與慢性發炎相關之生理與病理機轉研究，特別關注腸–肝–腎軸的整合性調控與腎臟功能惡化、代謝重編程、發炎免疫失衡之交互作用。本實驗室結合分子藥理學、免疫代謝學與微生物體學等跨領域方法，建立多種疾病模型（如高脂高糖飲食、膽管結紮、DSS 與 LPS 誘導）進行系統性探討，目標在於發掘關鍵訊號節點與具轉譯潛力的治療策略。

一、 腎臟生理與病理機制

本實驗室探索粒線體功能障礙與自噬失衡在腎損傷進展中的角色。聚焦於FXR 與 SIRT1等調控分子，解析其對腎功能維持與病理逆轉的潛力，作為未來精準介入策略的基礎。

二、腸–肝–腎軸訊號調控

研究腸道菌相與代謝物(如膽汁酸)於肝腎功能調節中的橋接角色，並驗證 FXR–Klotho–FGF 路徑於腸屏障保護與腫瘤環境調控中的作用，並探討具有調節腸道–肝臟–腎臟互通軸潛力的功能性介入策略。

三、肥胖與 MAFLD 之代謝調控

本實驗室聚焦於解析高脂高糖飲食造成的肝臟脂質毒性、粒線體失能與免疫代謝失衡等關鍵機轉，進一步探討其在代謝性脂肪肝疾病（MAFLD）進展中的系統性調控網絡。近期研究指出，Losartan 可藉由對 HIF-1α、巨噬細胞極化與粒線體功能的調節作用，為代謝性脂肪肝治療策略提供機轉依據。並建立整合性評估平台，以發掘具轉譯潛力之治療靶點。

四、腸道屏障與結腸炎調控

論文著作

1. Yang CW, Liu HM, Chang ZY, Liu GH, Chang HH, Huang PY, Lee TY. Puerarin Modulates Hepatic Farnesoid X Receptor and Gut Microbiota in High-Fat Diet-Induced Obese Mice. Int J Mol Sci. 2024 May 12;25(10):5274. doi: 10.3390/ijms25105274.

2. Liu HM, Chang ZY, Yang CW, Chang HH, Lee TY. Farnesoid X Receptor Agonist GW4064 Protects Lipopolysaccharide-Induced Intestinal Epithelial Barrier Function and Colorectal Tumorigenesis Signaling through the αKlotho/βKlotho/FGFs Pathways in Mice. Int J Mol Sci. 2023 Nov 29;24(23):16932. doi: 10.3390/ijms242316932.

3. Huang PY, Liu HM, Ko YR, Chang ZY, Lee TY. Electroacupuncture relieves portal hypertension by improving vascular angiogenesis and linking gut microbiota in bile duct ligation rats. Front Microbiol. 2023 Jul 11;14:1207137. doi: 10.3389/fmicb.2023.1207137.

4. Wang CH, Liu HM, Chang ZY, Lee MC, Hsu CH, Lee TY. Antioxidants Rich Herbal Formula Ger-Gen-Chyn-Lian-Tang Protects Lipotoxicity and Ameliorates Inflammation Signaling through Regulation of Mitochondrial Biogenesis and Mitophagy in Nonalcoholic Fatty Liver Disease Mice. Front Biosci (Landmark Ed). 2022 Aug 15;27(8):242. doi: 10.31083/j.fbl2708242.

5. Chou YT, Liu TT, Yang UC, Huang CC, Liu CW, Huang SF, Li TH, Liu HM, Lin MW, Yang YY, Lee TY, Huang YH, Hou MC, Lin HC. Intestinal SIRT1 Deficiency-Related Intestinal Inflammation and Dysbiosis Aggravate TNFα-Mediated Renal Dysfunction in Cirrhotic Ascitic Mice. Int J Mol Sci. 2021 Jan 27;22(3):1233. doi: 10.3390/ijms22031233.

6. Wang CH, Liu HM, Chang ZY, Huang TH, Lee TY. Losartan Prevents Hepatic Steatosis and Macrophage Polarization by Inhibiting HIF-1α in a Murine Model of NAFLD. Int J Mol Sci. 2021 Jul 22;22(15):7841. doi: 10.3390/ijms22157841.

7. Liu GH, Zhuo XC, Huang YH, Liu HM, Wu RC, Kuo CJ, Chen NH, Chuang LP, Lin SW, Chen YL, Yang HY, Lee TY. Alterations in Gut Microbiota and Upregulations of VPAC2 and Intestinal Tight Junctions Correlate with Anti-Inflammatory Effects of Electroacupuncture in Colitis Mice with Sleep Fragmentation. Biology (Basel). 2022 Jun 25;11(7):962. doi: 10.3390/biology11070962.

8. Chang ZY, Liu HM, Leu YL, Hsu CH, Lee TY. Modulation of Gut Microbiota Combined with Upregulation of Intestinal Tight Junction Explains Anti-Inflammatory Effect of Corylin on Colitis-Associated Cancer in Mice. Int J Mol Sci. 2022 Feb 28;23(5):2667. doi: 10.3390/ijms23052667.

9. Liu HM, Wang CH, Chang ZY, Huang TH, Lee TY. Losartan Attenuates Insulin Resistance and Regulates Browning Phenomenon of White Adipose Tissue in ob/ob Mice. Curr Issues Mol Biol. 2021 Oct 28;43(3):1828-1843. doi: 10.3390/cimb43030128.

10. Yeh CC, Liu HM, Lee MC, Leu YL, Chiang WH, Chang HH, Lee TY. Phytochemical‑rich herbal formula ATG‑125 protects against sucrose‑induced gastrocnemius muscle atrophy by rescuing Akt signaling and improving mitochondrial dysfunction in young adult mice. Mol Med Rep. 2022 Feb;25(2):57. doi: 10.3892/mmr.2021.12572.

11. Chen YS, Liu HM, Lee TY. Ursodeoxycholic Acid Regulates Hepatic Energy Homeostasis and White Adipose Tissue Macrophages Polarization in Leptin-Deficiency Obese Mice. Cells. 2019 Mar 16;8(3):253. doi: 10.3390/cells8030253.

12. Chang ZY, Chen CC, Liu HM, Yeh YC, Lin TY, Lee TY, Huang TH. Positive Effects of Ger-Gen-Chyn-Lian-Tang on Cholestatic Liver Fibrosis in Bile Duct Ligation-Challenged Mice. Int J Mol Sci. 2019 Aug 26;20(17):4181. doi: 10.3390/ijms20174181.

13. Huang TH, Chen CC, Liu HM, Lee TY, Shieh SH. Resveratrol Pretreatment Attenuates Concanavalin A-induced Hepatitis through Reverse of Aberration in the Immune Response and Regenerative Capacity in Aged Mice. Sci Rep. 2017 Jun 2;7(1):2705. doi: 10.1038/s41598-017-02881-z.

14. Liu HM, Liao JF, Lee TY. Farnesoid X receptor agonist GW4064 ameliorates lipopolysaccharide-induced ileocolitis through TLR4/MyD88 pathway related mitochondrial dysfunction in mice. Biochem Biophys Res Commun. 2017 Aug 26;490(3):841-848. doi: 10.1016/j.bbrc.2017.06.129.

15. Liu GH, Liu HM, Chen YS, Lee TY. Effect of Electroacupuncture in Mice with Dextran Sulfate Sodium-Induced Colitis and the Influence of Gut Microbiota. Evid Based Complement Alternat Med. 2020 Apr 27;2020:2087903. doi: 10.1155/2020/2087903.

16. Tsai YL, Liu CW, Hsu CF, Huang CC, Lin MW, Huang SF, Li TH, Lee KC, Hsieh YC, Yang YY, Lee TY, Liu HM, Huang YH, Hou MC, Lin HC. Obeticholic acid ameliorates hepatorenal syndrome in ascitic cirrhotic rats by down-regulating the renal 8-iso-PGF2α-activated COX-TXA2 pathway. Clin Sci (Lond). 2020 Aug 14;134(15):2055-2073. doi: 10.1042/CS20200452.

17. Li TH, Tsai YL, Hsu CF, Liu CW, Huang CC, Yang YY, Tsai HC, Huang SF, Hsieh YC, Liu HM, Lee TY, Hou MC, Tsai CY, Lin HC. Propranolol Is Associated with Lower Risk of Incidence of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Tertiary-Center Study and Indirect Comparison with Meta-Analysis. Gastroenterol Res Pract. 2020 Apr 9;2020:1892584. doi: 10.1155/2020/1892584.

18. Liu HM, Lee TY, Liao JF. GW4064 attenuates lipopolysaccharide‑induced hepatic inflammation and apoptosis through inhibition of the Toll‑like receptor 4‑mediated p38 mitogen‑activated protein kinase signaling pathway in mice. Int J Mol Med. 2018 Mar;41(3):1455-1462. doi: 10.3892/ijmm.2018.3366.