Treatment for biliary cirrhosis through GLP-1R/GCGR double-target-point agonist polypeptide
A technology of biliary cirrhosis and GLP-1R, applied in the field of biochemistry, can solve the problem of no clinical treatment, and achieve the effect of large safety window, small dosage, and easy to scale up production
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Embodiment 1
[0053] Embodiment 1, the synthesized polypeptide compound structure (Table 1) in the embodiment of the present invention:
[0054]
Embodiment 2
[0055] Example 2. In vitro inhibitory effect of GLP-1R / GCGR dual-target agonist polypeptide on liver fibrosis
[0056] The human hepatic stellate cell line LX-2 was selected to study and observe the effect of different doses of the test substance on the expression of the activation marker α-SMA of LX-2 cells.
[0057] Human hepatic stellate cells LX-2 were plated on a 35mm cell culture dish and cultured with DMEM (high glucose) + 10% FBS + 1% double antibody medium (Thermo Fisher) at 37°C, 5% CO 2 Under the conditions, when the cells grow to 70% confluence, there is no serum overnight, and in the morning of the next day, they are treated with the above-mentioned GLP-1R / GCGR dual agonist polypeptide 1-4 (dissolved in PBS) for 48 hours, and then the cell protein is extracted, and Western Blot is performed, and the β -actin was used as an internal reference, and the expression levels of α-SMA and β-actin were analyzed by Image J 1.50i gray scale. Negative control only added the ...
Embodiment 3
[0063] Example 3, GLP-1R / GCGR dual agonist polypeptides improve therapeutic effect on rat liver fibrosis induced by common bile duct ligation (BDL) (rat model of biliary cirrhosis)
[0064] 1. Test drugs: polypeptide compounds 1, 2, 3, 4 and liraglutide. Storage conditions -20°C.
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