阅读说明：本技术 田蓟苷在制备提高LXR-α的表达的药物中的应用 (Application of tilianin in preparation of medicine for improving expression of LXR-alpha ) 是由 于宁 郑瑞芳 邢建国 都研文 迪力努尔·艾力阿吉 热孜亚木·吾甫尔 于 2020-07-03 设计创作，主要内容包括：本发明公开了田蓟苷在制备提高LXR-α的表达的药物中的应用,属于医药技术领域,以H9c2心肌细胞缺氧/复氧(H/R)损伤为模型,以LXR-α作为分子靶标,确定了田蓟苷在LXR-α表达中的调控,为寻找开发有效地防治心脑血管疾病的药物提供了依据。(The invention discloses an application of tilianin in preparation of a drug for improving expression of LXR-alpha, belongs to the technical field of medicines, and provides a basis for searching and developing a drug for effectively preventing and treating cardiovascular and cerebrovascular diseases by taking H9c2 myocardial cell hypoxia/reoxygenation (H/R) injury as a model and LXR-alpha as a molecular target, determining regulation and control of tilianin in LXR-alpha expression.)

1. Application of tilianin in preparing medicine for improving expression of LXR-alpha is provided.

2. The use according to claim 1, wherein the use of tilianin or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising any of them for the manufacture of a medicament for increasing the expression of LXR- α.

Technical Field

The invention relates to a new application of tilianin, in particular to an application of tilianin in preparing a medicament for improving expression of LXR-alpha, belonging to the technical field of medicaments.

Background

Tilianin (Tilianin) is the main active ingredient of Dracocephalus moldavica L, a Uygur medicinal material in Xinjiang, and belongs to flavonoid compounds with the chemical name: acacetin-7-O-glucoside, molecular formula is C₂₂H₂₂O₁₀Molecular weight of 446.40, and structural formula as follows:

studies find that the tilianin has obvious protective effect on myocardial ischemia/reperfusion injury of rats and has obvious improvement effect on pathological states of atherosclerosis and the like of the rats.

Ischemic heart disease is the primary disease endangering human health, and although clinical treatment can improve the survival rate of patients by means of thrombolysis, interventional therapy, coronary artery bypass graft and the like, the subsequent ischemia/reperfusion injury (MIRI) aggravates myocardial injury and cardiac dysfunction, and obviously reduces the curative effect of coronary recanalization or perfusion reconstruction. Therefore, exploring an effective target point for resisting ischemia/reperfusion injury and developing a novel high-efficiency low-toxicity prevention and treatment medicine become the most active hot points in cardiovascular medicine research and development and clinical cardiology.

Liver X Receptors (LXRs) are members of the nuclear receptor family, and mainly have the effects of inhibiting cell inflammation and apoptosis, regulating fat metabolism and carbohydrate metabolism in vivo and the like. In the research of cardiovascular aspect, LXRs are found to be closely related to ischemia/reperfusion injury, reverse cholesterol transport, atherosclerosis, myocardial hypertrophy and the like.

LXRs include two homologous subtypes, LXR-alpha and LXR-beta. LXR-alpha and LXR-beta are both expressed in normal myocardial tissue, but LXR-alpha is significantly upregulated during ischemia/reperfusion, while LXR-beta is unchanged. Recent studies have shown that LXRs agonists administered can significantly reduce apoptosis and infarct size and improve contractile function. The research on action mechanism shows that LXRs can be activated to obviously improve the oxidative stress, the nitrification stress and the inflammatory response of myocardial tissues in the myocardial ischemia/reperfusion process, and inhibit endoplasmic reticulum stress and a mitochondrion-mediated endogenous apoptosis program by reducing the phosphorylation of p38MAPK and increasing the phosphorylation signal paths of Akt and ERK for promoting cell survival.

Further studies have found that LXR- α inhibits endoplasmic reticulum stress and mitochondrially mediated endogenous apoptotic programs during myocardial ischemia/reperfusion injury through antioxidant/nitrification stress and anti-inflammatory effects. Therefore, LXR-alpha is an important defense factor of an organism against myocardial ischemia/reperfusion injury, and can become a novel molecular target for treating ischemic heart disease. Therefore, targeting the LXR-alpha signal transduction pathway provides an effective target and a key pathway for the research of the medicine for resisting myocardial ischemia/reperfusion injury.

In this context, it is of great interest to find compounds that are modulators of LXRs receptor activity.

Disclosure of Invention

In view of the above, the invention provides the application of tilianin in the preparation of the drug for improving the expression of LXR-alpha, the regulation and control of tilianin in LXR-alpha expression are determined by taking H9c2 myocardial cell hypoxia/reoxygenation (H/R) injury as a model and LXR-alpha as a molecular target, and a basis is provided for the search and development of the drug for effectively preventing and treating cardiovascular and cerebrovascular diseases.

In order to achieve the purpose, the technical scheme of the invention is as follows:

application of tilianin in preparing medicine for improving expression of LXR-alpha is provided.

In particular to application of tilianin or pharmaceutically acceptable salts thereof or a pharmaceutical composition containing any one of them in preparing a medicament for improving expression of LXR-alpha.

Drawings

FIG. 1 is a diagram of the morphology of cells observed by an inverted fluorescence microscope in example 1 of the present invention;

FIG. 2 is a graph showing the effect of tilianin on H9c2 cell survival rate of H/R after GSK2033 stem prognosis in example 2 of the present invention;

FIG. 3 is a graph showing the results of the inhibition of H9c2 apoptosis of H/R after GSK2033 stem prognosis by tilianin in example 3 of the present invention;

FIG. 4 is a graph showing the effect of qRT-PCR detection of different drug interventions on the expression level of LXR alpha mRNA of H9c2 cells in example 4 of the present invention;

FIG. 5 is a graph showing the effect of different pharmacological interventions on the levels of LXR-alpha protein in H9c2 cells in accordance with example 5 of the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.