Innovative Pharmacology Research, LLC, Tomsk, Russia.
Siberian State Medical University, Ministry of Health of the Russian Federation, Tomsk, Russia.
Bull Exp Biol Med. 2023 Jan;174(3):333-336. doi: 10.1007/s10517-023-05703-7. Epub 2023 Feb 1.
We studied the effect of an indolinone derivative GRS on the development of experimental atherosclerosis in C57BL/6 mice. Atherosclerosis was modeled by intraperitoneal administration of endothelial lipoprotein lipase inhibitor Kolliphor P 407 micro Geismar over 5 months. GRS was administered orally in a dose of 10 mg/kg once a day throughout the experiment. In 5 months, the levels of total cholesterol, LDL, and triglycerides in blood serum, as well as histological composition of the ascending aorta were studied. In mice with experimental atherosclerosis, we observed pronounced dyslipidemia with an increase in serum cholesterol, LDL, and triglycerides and accumulation of xanthoma cells in the aorta wall. Repeat administration of GRS did not eliminate dyslipidemia, but prevented an increase in the number of xanthoma cells in the aorta wall (p<0.05). The stimulator of soluble guanylate cyclase GRS did not exhibit hypolipidemic activity, but restored impaired endothelial function in the atherosclerosis model and prevented atherosclerotic damage to blood vessels and vascular wall remodeling.
我们研究了吲唑酮衍生物 GRS 对 C57BL/6 小鼠实验性动脉粥样硬化发展的影响。通过腹腔内给予内皮脂蛋白脂肪酶抑制剂 Kolliphor P 407 micro Geismar，5 个月内建立动脉粥样硬化模型。GRS 以 10mg/kg 的剂量每天口服一次，整个实验过程中给予。在 5 个月时，研究了血清总胆固醇、LDL 和甘油三酯水平以及升主动脉的组织学组成。在实验性动脉粥样硬化的小鼠中，我们观察到明显的血脂异常，血清胆固醇、LDL 和甘油三酯升高，主动脉壁中黄瘤细胞堆积。重复给予 GRS 并没有消除血脂异常，但防止了主动脉壁中黄瘤细胞数量的增加（p<0.05）。可溶性鸟苷酸环化酶刺激剂 GRS 没有表现出降低血脂的活性，但恢复了动脉粥样硬化模型中受损的内皮功能，并防止了血管粥样硬化损伤和血管壁重塑。
