Liraglutide作為長(zhǎng)效GLP-1R激動(dòng)劑在代謝及纖維化研究中的應(yīng)用

Liraglutide（利拉魯肽，AbMole，M45167）是一種長(zhǎng)效的人源化GLP-1類似物，通過激活GLP-1受體（GLP-1R），調(diào)節(jié)cAMP-PKA路徑影響代謝，如激活A(yù)MPK信號(hào)以改善能量代謝和抑制細(xì)胞凋亡。在細(xì)胞實(shí)驗(yàn)中，Liraglutide（CAS No.：204656-20-2）在SH-SY5Y人神經(jīng)母細(xì)胞瘤細(xì)胞（10-100nM）中減輕β-淀粉樣蛋白引起的毒性并逆轉(zhuǎn)胰島素抵抗[1]，Liraglutide在MC3T3-E1小鼠成骨細(xì)胞（100 nM）中促進(jìn)成骨分化和增加堿性磷酸酶活性[2]，在HepG2人肝癌細(xì)胞（以1-1000 nM的濃度進(jìn)行實(shí)驗(yàn)）抑制細(xì)胞增殖和誘導(dǎo)G1/S期停滯[3]。Liraglutide（利拉魯肽）還能抑制βTC-6小鼠β細(xì)胞由血清剝奪誘導(dǎo)的細(xì)胞凋亡。Liraglutide還是研究動(dòng)物代謝的重要工具。

Liraglutide能用于C57BL/6J小鼠肥胖模型（1mg/kg劑量）并改善高脂飲食誘導(dǎo)的代謝紊亂以及調(diào)節(jié)腸道菌群[4]，Liraglutide還在大鼠糖尿病模型（Alloxan 或Streptozotocin（STZ）誘導(dǎo)）減輕了體重和改善血糖控制[5-7]。Liraglutide還能在Sprague Dawley大鼠心肌梗死模型改善心臟功能和減少心肌纖維化[8]。并且Liraglutide在Sprague Dawley大鼠肌肉萎縮模型（200μg/kg/day皮下注射）中成功激活cAMP信號(hào)抑制萎縮[9]。Liraglutide還具有一定的抗纖維化活性，在大鼠肺纖維化模型（Bleomycin誘導(dǎo)）中成功減少了膠原表達(dá)[10]。

參考文獻(xiàn)及鳴謝
[1] Jantrapirom, S.; Nimlamool, W.; Chattipakorn, N.; et al. Liraglutide Suppresses Tau Hyperphosphorylation, Amyloid Beta Accumulation through Regulating Neuronal Insulin Signaling and BACE-1 Activity. International journal of molecular sciences 2020, 21 (5).
[2] Sun, Y.; Liang, Y.; Li, Z.; et al. Liraglutide Promotes Osteoblastic Differentiation in MC3T3-E1 Cells by ERK5 Pathway. International journal of endocrinology 2020, 2020, 8821077.
[3] Kapodistria, K.; Tsilibary, E. P.; Kotsopoulou, E.; et al. Liraglutide, a human glucagon-like peptide-1 analogue, stimulates AKT-dependent survival signalling and inhibits pancreatic beta-cell apoptosis. Journal of cellular and molecular medicine 2018, 22 (6), 2970-2980.
[4] Zhao, L.; Chen, Y.; Xia, F.; et al. A Glucagon-Like Peptide-1 Receptor Agonist Lowers Weight by Modulating the Structure of Gut Microbiota. Frontiers in endocrinology 2018, 9, 233.
[5] Mathieu, C.; Zinman, B.; Hemmingsson, J. U.; et al. Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial. Diabetes care 2016, 39 (10), 1702-1710.
[6] Cai, H.; Zhou, L.; Liu, J.; et al. Independent and combined effects of liraglutide and aerobic interval training on glycemic control and cardiac protection in diabetic cardiomyopathy rats. Biochemical and biophysical research communications 2022, 629, 112-120.
[7] Zhao, X. Y.; Yu, T. T.; Liu, S.; et al. Effect of liraglutide on endoplasmic reticulum stress in the renal tissue of type 2 diabetic rats. World journal of diabetes 2020, 11 (12), 611-621.
[8] Huang, D. D.; Huang, H. F.; Yang, Q.; et al. Liraglutide improves myocardial fibrosis after myocardial infarction through inhibition of CTGF by activating cAMP in mice. European review for medical and pharmacological sciences 2018, 22 (14), 4648-4656.
[9] Gurjar, A. A.; Kushwaha, S.; Chattopadhyay, S.; et al. Long acting GLP-1 analog liraglutide ameliorates skeletal muscle atrophy in rodents. Metabolism: clinical and experimental 2020, 103, 154044.
[10] Yang, X.; Ma, X.; Don, O.; et al. Mesenchymal stem cells combined with liraglutide relieve acute lung injury through apoptotic signaling restrained by PKA/beta-catenin. Stem cell research & therapy 2020, 11 (1), 182.