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Application of histone deacetylase inhibitor in treating atherosclerosis

A technology of atherosclerosis and sirtuin, which is applied in the direction of drug combination, amide active ingredients, medical preparations containing active ingredients, etc., and can solve the problems that the regulatory mechanism needs to be further clarified

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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The mechanism of positive cholesterol transport regulated by LDLR was first revealed, and the mechanism related to the reverse cholesterol transport process has only been revealed in recent years, and there are still many regulatory mechanisms to be further elucidated

Method used

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  • Application of histone deacetylase inhibitor in treating atherosclerosis
  • Application of histone deacetylase inhibitor in treating atherosclerosis
  • Application of histone deacetylase inhibitor in treating atherosclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0076] Example 2 Screening model for up-regulators of high-density lipoprotein receptor expression Determination of 9179A and trichostatin A standard substances up-regulate high-density lipoprotein receptor expression activity

[0077] A) Construction of recombinant expression plasmid pGL3-CLAP

[0078] Strains and cell lines

[0079] E. coli DH5α was used for genetic manipulation of plasmid DNA. The human liver cancer cell line HepG2 (purchased from Shanghai Wuli Biotechnology Co., Ltd.) was used to construct a screening model for up-regulators of human high-density lipoprotein receptor expression.

[0080] plasmid

[0081] pGEM-T (purchased from Promega) was used for cloning of PCR products. pGL3-Basic (purchased from Promega Company) is a reporter gene vector containing a firefly (Photinus pyralis) luciferase coding gene without a promoter, and is used for cloning of human high-density lipoprotein receptor regulatory sequence.

[0082] pGL3-control (purchased from Prome...

Embodiment 3

[0109] Example 3: Effect of trichostatin A on high-density lipoprotein receptor CLA-1 in liver cancer cells HepG2

[0110] A) HepG2 cell culture

[0111] MEM-EBSS medium (Hyclone Company) (containing 10% standard fetal bovine serum ) was used for the cultivation of liver cancer cell HepG2.

[0112] B) Using real-time quantitative RT-PCR to study the effect of trichostatin A on the transcription level of CLA-1

[0113] (1) Extraction of total cellular RNA

[0114] Human hepatoma cells HepG2 at 5×10 5 Inoculate 60mm cell culture plates at 37°C, 5% CO 2 After culturing for 24 hours under the same conditions, the cells were rinsed twice with ice-cold PBS, and serum-free MEM-EBSS medium containing 0.03, 0.3, 0.6 μM (DMSO content: 0.1%) trichostatin A was added respectively. The corresponding medium containing 0.1% DMSO was added to the control plate. 37°C, 5% CO 2 After culturing for 24 hours under the condition, the total cellular RNA was extracted with Trizol reagent (Invit...

Embodiment 4

[0142]Example 4 Effect of trichostatin A on high-density lipoprotein receptor SR-BI in RAW 264.7 cells

[0143] A) Culture of RAW 264.7 cells

[0144] DMEM-high glucose medium (Hyclone Company) (containing 10% standard fetal bovine serum ) was used for culturing mouse macrophage RAW 264.7.

[0145] B) Real-time PCR determination of the effect of trichostatin A on the level of SR-BI mRNA in RAW 264.7 cells

[0146] As described in A) in embodiment 3, experimental result sees attached Figure 7 , Trichostatin A can dose-dependently up-regulate the level of SR-BI gene mRNA in RAW 264.7 cells, and the up-regulation rates of 0.3μM and 0.6μM Trichostatin A were 45.0% and 64.8%, respectively.

[0147] C) Western blot method to determine the effect of trichostatin A on SR-BI protein level in RAW 264.7 cells

[0148] (1) Preparation of protein samples

[0149] Mouse macrophage RAW 264.7 in 7×10 5 Cells / ml inoculated on 60mm cell culture plate, 37°C, 5% CO 2 After culturing under ...

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Abstract

The invention relates to application of a histone deacetylase inhibitor compound in preparing a medicament for treating and / or preventing atherosclerosis by strengthening a reverse cholesterol transport mechanism, wherein a histone deacetylase inhibitor is trichostatin A shown in a formula 1 or suberoylanilide hydroxamic acid shown in a formula 2.

Description

field of invention [0001] The invention relates to histone deacetylase inhibitor compounds trichostatin A (Trichostatin A, TSA) and suberoylanilide hydroxamic acid (Sueroylanilidehydroxamicacid, SAHA) for the preparation of therapeutic and / or the use of drugs for preventing atherosclerosis, wherein the drugs for treating and / or preventing atherosclerosis by enhancing the cholesterol reverse transport mechanism include drugs for up-regulating the expression activity of high-density lipoprotein receptor CLA-1 / SR-BI and drugs that upregulate the expression activity of the ATP-binding cassette transporter ABCA1. Background of the invention [0002] Cardiovascular disease has become a common disease that threatens human life in today's world, and atherosclerosis (AS) is its main pathological basis. Epidemiological and clinical studies have shown that the concentration of cholesterol in plasma and its metabolism in the body are closely related to the occurrence and development o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/167A61K31/16A61K31/4439A61P9/10
Inventor 洪斌司书毅杨媛鲍羿王丽高磊姜威王丽非
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