阅读说明：本技术 一种P53抑制剂Pifithrin-α在拮抗心脏纤维化的新用途 (New application of P53 inhibitor Pifithrin- α in antagonizing cardiac fibrosis ) 是由 周浩 胡杰 于 2019-12-12 设计创作，主要内容包括：本发明模拟心脏纤维化的病理过程,构建异丙肾上腺素刺激下的SD大鼠心脏纤维化模型,公开一种可以抑制心脏纤维化的P53抑制剂Pifithrin-α,通过检测血流动力学参数、心脏指数、心肌组织的HE染色、Masson染及心肌胶原容积分数(CVF),确定P53抑制剂Pifithrin-α可以减轻异丙肾上腺素引起的SD大鼠的心脏纤维化。因此提出了通过P53抑制剂Pifithrin-α可调控心脏纤维化的进程,发挥心脏抗纤维化的治疗作用,这对心脏纤维化的治疗具有重要的意义。(The invention simulates the pathological process of cardiac fibrosis, constructs an SD rat cardiac fibrosis model under the stimulation of isoproterenol, discloses a P53 inhibitor Pifithrin- α capable of inhibiting cardiac fibrosis, and determines that the P53 inhibitor Pifithrin- α can relieve the cardiac fibrosis of the SD rat caused by isoproterenol by detecting the hemodynamic parameters, cardiac indexes, HE staining, Masson staining and myocardial Collagen Volume Fraction (CVF).)

1. A new use of P53 inhibitor Pifithrin- α in antagonizing cardiac fibrosis is provided.

2. The use according to claim 1, wherein the P53 inhibitor Pifithrin- α is capable of improving isoproterenol-induced SD rat myocardial fibrosis.

3. The use according to claim 2, wherein the treatment with isoproterenol alters the hemodynamic parameters of SD rats and the further addition of the P53 inhibitor Pifithrin- α improves the hemodynamic parameters of SD rats treated with isoproterenol, the treatment with isoproterenol increases the cardiac index of SD rats and the further addition of the P53 inhibitor Pifithrin- α reduces the cardiac index of SD rats treated with isoproterenol, the treatment with isoproterenol causes myocardial fibrosis in SD rats and the further addition of the P53 inhibitor Pifithrin- α improves the myocardial fibrosis in SD rats treated with isoproterenol, the treatment with isoproterenol increases the myocardial collagen volume fraction in SD rats and the further addition of the P53 inhibitor Pifithrin- α reduces the myocardial collagen volume fraction in SD rats treated with isoproterenol.

Technical Field

The invention belongs to the technical field of new application of bioactive substances, and particularly relates to new application of a bioactive preparation in antagonism and intervention on cardiac fibrosis.

Background

For a long time, clinicians and researchers have tended to consider cardiac fibrosis as an inevitable "ultimate common pathway" after damage to cardiac tissue from a variety of causes. In the process, the scar tissue is greatly proliferated, wherein the myocardial extracellular matrix is deposited in the interstitium, the normal myocardial structure is damaged, the morphology of the heart is changed, and the diastolic dysfunction of the heart is caused, so that a series of structural functions such as cardiac sclerosis, myocardial cell atrophy, arrhythmia and the like are changed. Therefore, in the treatment of heart diseases, how to block this process by bioactive agents becomes an alternative to antagonizing cardiac fibrosis.

Pifithrin- α, linear fraction thereofSub-formula is C₁₆H₁₉BrN₂OS. the bioactive preparation mainly inhibits the transcriptional activity of P53 to prevent apoptosis, and the research of in vitro level shows that Pifithrin- α can inhibit glucose oxidase to promote the dissolution of P53 protein in cells, meanwhile, Pifithrin- α can inhibit the decomposition of glucose oxidase to bcl-2 protein to strengthen the anti-apoptosis effect of bcl-2 protein, however, the mechanism of inhibiting apoptosis of P53 dependent pathway of Pifithrin- α is not clear at present, furthermore, Pifithrin- α is used as receptor (AhR) agonist of aryl hydrocarbon, the capability of Pifithrin-OS. depends on the capability of binding AhR, Pifithrin- α can induce the formation of DNA binding complex to enhance the activity of receptor by combining with AhR, and the classical target gene CYP1A1 is up-regulated to play a biological role.

Sprague-Dawley (SD) rat is an important model organism, and is widely used as a research object in the research of physiology, heredity, molecular mechanism, pathology, toxicology and the like. The SD rat has the characteristics of strong behavioral homogeneity, short experimental period, strong reproductive capacity, clear genetic background, mature molecular operation, obvious character characterization and the like, so the SD rat is an experimental material which is widely accepted and has strong accurate characterization capacity. The experimental evidence in the technical scheme disclosed by the invention is obtained by taking SD rats as experimental materials.

Disclosure of Invention

The invention aims to provide a new application of P53 inhibitor Pifiturin- α in antagonizing cardiac fibrosis.

The invention provides a new application of P53 inhibitor Pifithrin- α in antagonizing cardiac fibrosis.

Further, the P53 inhibitor Pifithrin- α can improve isoproterenol-induced SD rat myocardial fibrosis.

Further, isoproterenol treatment altered the hemodynamic parameters of SD rats, while further addition of the P53 inhibitor Pifithrin- α improved the hemodynamic parameters of isoproterenol treated SD rats, isoproterenol treatment increased the cardiac index of SD rats, while further addition of the P53 inhibitor Pifithrin- α decreased the cardiac index of isoproterenol treated SD rats, isoproterenol treatment resulted in myocardial fibrosis in SD rats, while further addition of the P53 inhibitor Pifithrin- α improved myocardial fibrosis in isoproterenol treated SD rats, isoproterenol treatment increased the myocardial collagen volume fraction of SD rats, while further addition of the P53 inhibitor Pifithrin- α decreased the myocardial collagen volume fraction of isoproterenol treated SD rats.

Compared with the prior art, the technical scheme provided by the invention has the following advantages:

the P53 inhibitor Pifitrin- α is applied to antagonize isoproterenol-treated SD rat myocardial fibrosis for the first time, and is a new application of the P53 inhibitor Pifitrin- α in function, and the P53 inhibitor Pifitrin- α is never applied to the improvement of cardiac fibrosis, so that the technical effect of the P53 inhibitor Pifitrin- α on the myocardial fibrosis, myocardial Collagen Volume Fraction (CVF), hemodynamic parameters, cardiac index and other indexes of SD rats is remarkable and difficult to expect.

Drawings

FIG. 1 is a graph of paraffin section HE staining of three groups of animal myocardial tissue samples of example 1;

figure 2 is a Masson stain of paraffin sections and myocardial Collagen Volume Fraction (CVF) statistical plot of three groups of animal myocardial tissue samples from example 2.

Detailed Description

The present invention is further illustrated by the following examples, which are not intended to limit the invention to these embodiments. It will be appreciated by those skilled in the art that the present invention encompasses all alternatives, modifications and equivalents as may be included within the scope of the claims.