CN-121971424-A - Method for regulating and controlling pathological cardiac remodeling of AAC model mice by succinic acid

Abstract

The invention discloses a method for regulating and controlling AAC model mice to manage cardiac remodeling by succinic acid, and belongs to the field of cardiac disease treatment. The method comprises the following steps of selecting 8-week-old male C57BL/6J mice, adaptively feeding the mice into a normal temperature group and a slightly cold exposure group, establishing a cardiac remodeling model through AAC operation, performing 1.5% succinic acid aqueous solution and/or 1mg/mL broad-spectrum antibiotic intervention on the mice for 4 weeks, collecting cardiac tissues, detecting cardiac remodeling related indexes through methods such as Masson staining, WGA staining, qPCR, western blot and the like, and evaluating the intervention effect. According to the invention, succinic acid is used for intervention in a slight cold exposure environment, so that the pathological cardiac remodeling of the AAC model mice is effectively regulated and controlled, and a novel method and thought are provided for the research and treatment of cardiac remodeling diseases.

Inventors

• ZHOU YING
• DUAN QIONG
• WANG XIN
• Cheng Banghong
• XU NUO

Assignees

• 南昌大学第一附属医院

Dates

Publication Date

20260505

Application Date

20260126

Claims (9)

1. 1. A method for succinic acid to regulate pathological cardiac remodeling in an AAC model mouse, comprising the steps of: step one, selecting 8-week-old male C57BL/6J mice, randomly dividing the mice into 6 groups, and placing the mice in normal temperature and slight cold exposure environments for adaptive feeding for 1 week; Step two, carrying out anesthesia treatment on the mice, and establishing a cardiac remodeling model through AAC operation; Step three, performing 1.5% succinic acid aqueous solution and/or 1mg/mL broad-spectrum antibiotic intervention on the mice according to the grouping for 4 weeks; And step four, collecting heart tissues, detecting heart remodeling related indexes, and evaluating the intervention effect.
2. 2. The method of claim 1, wherein in step one, the 6 mice are normal temperature control group, normal temperature succinic acid group, normal temperature succinic acid+broad spectrum antibiotic group, slightly cold exposure control group, slightly cold exposure succinic acid group, slightly cold exposure succinic acid+broad spectrum antibiotic group, respectively.
3. 3. The method according to claim 1, wherein in step two, the anesthetic treatment is performed by injection Zoletil and/or xylazine.
4. 4. The method of claim 1, wherein in step two, the AAC procedure comprises exposing the abdominal aorta using a 27G needle as a stent, knotting the abdominal aorta, and then removing the needle to form a standardized vascular stenosis.
5. 5. The method of claim 1, wherein in step three, 1.5% aqueous succinic acid and/or 1mg/mL broad spectrum antibiotic is administered via drinking water, all being free to drink for 4 weeks.
6. 6. The method of claim 1, wherein in step three, the aqueous succinic acid solution is a sterile aqueous succinic acid salt solution.
7. 7. The method according to claim 1, wherein in step three, the broad-spectrum antibiotic is gentamicin and/or vancomycin.
8. 8. The method according to claim 1, wherein in the fourth step, the detection means comprises Masson's staining for evaluating the degree of myocardial fibrosis, WGA's staining for measuring the surface area of myocardial cells, qPCR for detecting the level of fibrosis-related gene expression, and Western blot for detecting the level of fibrosis-related protein expression.
9. 9. The method of claim 8, wherein the fibrosis-related genes include, but are not limited to ANP, BNP, ANKRD, fn1, and MYH7, and the fibrosis-related proteins include, but are not limited to, ANKRD1, and BNP.

Description

Method for regulating and controlling pathological cardiac remodeling of AAC model mice by succinic acid Technical Field The invention relates to the field of heart disease treatment, in particular to a method for regulating and controlling pathological cardiac remodeling of an AAC model mouse by succinic acid. Background Along with the continuous rising of the incidence rate of cardiovascular diseases, pathological cardiac remodeling has become an important pathological basis of cardiovascular diseases, and an abdominal aortic stenosis (Abdominal Aortic Constriction, AAC) model is a classical animal model for researching pathological cardiac remodeling, and can effectively simulate the increase of cardiac pressure load so as to trigger pathological changes such as myocardial hypertrophy, myocardial fibrosis and the like. The environmental temperature is an important external stress factor, and can regulate and control heart pathological changes by affecting organism metabolism, neuroendocrine and intestinal flora steady state, however, the heart remodeling process and the regulation mechanism of an AAC model mouse have not been fully studied under a slightly cold exposure environment (16+/-1 ℃). Succinic acid has been found in recent years to play an important regulatory role in a variety of physiological pathological processes as a key intermediate of the tricarboxylic acid cycle. There are studies showing that succinic acid participates in various ways such as energy metabolism and immune regulation to affect functions of tissues and organs, but the regulation effect of succinic acid on cardiac remodeling under specific temperature (especially slight cold exposure) and AAC-induced pathological model is not clear, meanwhile, the mediating effect of intestinal flora on metabolic regulation of cardiac pathological changes is gradually focused, but no study has been revealed whether succinic acid reduces the pathological cardiac remodeling of AAC model mice by regulating intestinal flora (such as specific flora abundance), and in intestinal flora study, broad-spectrum antibiotics are often used as intervention means to evaluate the influence of intestinal flora on the regulation process. Therefore, a reliable research method is needed, and a novel experimental model and an action target point are provided for preventing and treating pathological cardiac remodeling by revealing the regulation and control effect of succinic acid on the pathological cardiac remodeling of an AAC model mouse under a slight cold exposure environment and the mediating mechanism of intestinal flora in the process of regulating the pathological cardiac remodeling by succinic acid. Disclosure of Invention In order to solve the technical problems that in the prior art, a clear understanding of a pathological cardiac remodeling mechanism of a succinic acid regulation AAC model mouse is lacking, an action mechanism of the succinic acid regulation AAC model mouse in a slightly cold exposure environment is not yet clarified, a mediating effect of intestinal flora in a metabolite regulation cardiac pathological change is not clear, and meanwhile, the existing research lacks standardized and reproducible experimental models and schemes, the invention provides a method for regulating the pathological cardiac remodeling of the succinic acid regulation AAC model mouse, and the method realizes effective intervention on the pathological cardiac remodeling of the mouse. The technical scheme adopted for solving the technical problems is that the method for regulating and controlling pathological cardiac remodeling of mice with AAC model by succinic acid comprises the following steps: step one, selecting 8-week-old male C57BL/6J mice, randomly dividing the mice into 6 groups, and respectively placing the mice in normal temperature (illustrated by 23+/-1 ℃ in an exemplary manner) and slight cold exposure (illustrated by 16+/-1 ℃ in an exemplary manner) environments for adaptively feeding the mice for 1 week; Step two, carrying out anesthesia treatment on the mice, and establishing a cardiac remodeling model through AAC operation; Step three, performing 1.5% succinic acid aqueous solution and/or 1mg/mL broad-spectrum antibiotic intervention on the mice according to the grouping for 4 weeks; And step four, collecting heart tissues, detecting heart remodeling related indexes, and evaluating the intervention effect. Preferably, in the first step, the 6 groups of mice are respectively a normal temperature control group, a normal temperature succinic acid group, a normal temperature succinic acid+broad-spectrum antibiotic group, a slight cold exposure control group, a slight cold exposure succinic acid group and a slight cold exposure succinic acid+broad-spectrum antibiotic group. Preferably, in the second step, the anesthesia treatment is performed by injection Zoletil (sultai-50, the injection dose is exemplified by 50 mg/kg) and/or xylazine (the injecti