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Hepatic Cell Micro RNA-122 (miR-122) can Lower Blood Lipid and Inhibit the Apoptosis of Nerve Cells in Cerebral Infarct by 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR): A Clinical and Laboratory Animal Study
Vol 36, Issue 6, 2022
Abstract
Background: This study aimed to explore the correlation of micro RNA-122 (miR-122) levels with blood lipid and the mechanism of action, and to verify the correlation of 3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) levels with sterol concentration, cerebral infarct (CI) and hyperlipidemia. The study tried to provide a new therapeutic target for the prevention and treatment of brain nerve cell injury and even CI caused by hyperlipidemia. Methods: Clinical cases of hyperlipidemia were retrospectively collected to analyze the correlation of hyperlipidemia with CI using a cohort study. Mice were grouped to construct a mouse model of hyperlipidemia. All mice were injected intraperitoneally with 25 µg/kg saline, miR-122 antagomiR daily. Area with CI in the brain was measured by after 14 days, and the infected tissues were collected. Serum lipid parameters were measured with automatic biochemical analyzer. Grouped culture was conducted with liver cell lines. miR-122 expression in liver tissues and liver cells cultured in vitro was checked for with qRT-PCR. Luciferase reporter gene demonstrated the interaction between miR-122 with HMGCR. HMGCR expression in liver cells cultured in vitro, and caspase3, cleaved caspase3, Bcl-2 and Bax expression in brain tissues were analyzed by Western blot. Results: Hyperlipidemia was a risk factor for CI. Blood lipid detection showed significantly increased blood lipid in mice with hyperlipidemia after modogenesis, and decreased blood lipid after inhibiting miR-122. CI in mice with hyperlipidemia significantly improved after inhibiting miR-122. Luciferase reports and Western blot results showed that miR-122 regulated blood lipid by targeting HMGCR and subsequently improved CI. Conclusions: miR-122 targeting HMGCR plays an important role in the regulation of blood lipids. Inhibition of miR-122 can reduces the expression of HMGCR and then reduce blood lipids and reduce neuronal apoptosis in cerebral infarction.
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Copyright (c) 2022 Shiyuan Xie, Zaihong Lin, Guangping Zhang, Shu Du, Yan Jiang, Jing Liu, Tuantuan Chen, Zenghui Fu, Huili Yu, Yulei Yang, Yan Jin
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Medical Genetics, University of Torino Medical School, Italy
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy