Application of nuclear receptor ROR alpha in preparation of anti-heart failure drugs

A heart failure and nuclear receptor technology, applied in the field of biomedicine, can solve the problems of poor efficacy of drugs for the treatment and prevention of heart failure

Inactive Publication Date: 2018-12-07
RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] The object of the present invention is to provide a nuclear receptor RORα in the preparation of anti-heart failure drugs, the application of the nuclear receptor RORα in t

Method used

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  • Application of nuclear receptor ROR alpha in preparation of anti-heart failure drugs
  • Application of nuclear receptor ROR alpha in preparation of anti-heart failure drugs
  • Application of nuclear receptor ROR alpha in preparation of anti-heart failure drugs

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Experimental program
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Effect test

Embodiment 1

[0028] The establishment of embodiment 1 mouse myocardial pathological hypertrophy model

[0029] 10-12-week-old mice were put into an anesthesia tank, and anesthetized by continuous inhalation of 2% isoflurane through an anesthesia machine (ventilation rate 2 L / min). The endotracheal tube was connected to a ventilator to maintain breathing. The surgical area was cleaned, and a median anterior chest incision was made to open the thoracotomy to the second rib, the thymus was separated, and the aortic arch was exposed. Use a 27G pad needle to prick, and use 7-0 nylon surgical suture to ligate the aorta and pad needle together. After the ligation is confirmed, pull out the pad needle, close the chest layer by layer, and sew the skin. After the spontaneous breathing of the mice recovered, the tracheal intubation was removed, and the mice were placed on a constant temperature heating blanket until they woke up from anesthesia. The aortic arch ligation was not performed in the sha...

Embodiment 2

[0033] Small animal echocardiographic evaluation:

[0034] The mice were anesthetized by continuous inhalation of 2% isoflurane and fixed in the supine position on the ultrasonic examination table with built-in heating function. A 30MHz high-frequency probe collects parasternal long-axis views and apical four-chamber views on the chest wall, records electrocardiograms, and measures heart rate. Two-dimensional ultrasonographic images were obtained at the level of the papillary muscle under the mitral valve in the parasternal left ventricular short-axis view, and left ventricular end systolic internal diameters (LVIDs), left ventricular end diastolic internal diameters (LVIDd), left ventricular ejection fraction (LVEF) and left ventricular ejection fraction (LVEF) were measured. Shortened Fraction (LVFS). The instrument parameter settings for mouse examination in each group remained the same, and the image acquisition and calculation were performed by the same person, and the a...

Embodiment 3

[0038] The full-length cDNA sequence of mouse RORα was integrated downstream of the mouse α-myosin heavy chain promoter to construct cardiomyocyte-specific RORα overexpressing mice (TG) in C57BL / 6J background. 10-12 weeks old SPF grade RORα-TG mice and their control mice (NTG) were randomly divided into TAC group and Sham group. A series of related tests were carried out 8 weeks after TAC, and it was found that the cross-section of cardiomyocytes in RORα-TG mice was reduced, the weight of the heart was significantly reduced, and the heart function was improved ( image 3 ).

[0039] in image 3 A is the representative HE staining picture of each group; image 3 B is the quantitative result of the cross-sectional area of ​​cardiomyocytes in each group; image 3 C is the statistical result of heart weight and body weight ratio; image 3 D is the fraction of left ventricle shortening measured by echocardiography of small animals in each experimental group.

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Abstract

The invention provides application of a nuclear receptor ROR alpha in the preparation of anti-heart failure drugs. The nuclear receptor ROR alpha is a nuclear receptor ROR alpha 1 subtype; the gene sequence of the nuclear receptor ROR alpha 1 is as shown in SEQ ID NO. 1; and the amino acid sequence of the nuclear receptor ROR alpha 1 is as shown in SEQ ID NO. 2. Experiments find that the expression of the nuclear receptor ROR alpha provided by the invention in hypertrophic and failing myocardial tissues is down-regulated, and the loss of ROR alpha can aggravate cardiac hypertrophy and cardiacfailure. The overexpression of myocardial-specific ROR alpha can alleviate TAC-induced myocardial interstitial fibrosis and improve the cardiac hypertrophy and cardiac failure. The nuclear receptor ROR alpha has an effect against cardiac hypertrophy and cardiac failure.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to cardiovascular drugs, in particular to the application of a nuclear receptor RORα in the preparation of anti-heart failure drugs. Background technique [0002] Heart failure is the severe and terminal stage of various heart diseases, with a high incidence rate, and is one of the most important cardiovascular diseases today. Heart failure is the leading cause of mortality in industrialized countries and caused an estimated $108 billion in global economic losses in 2012 alone. Heart failure refers to a group of complex clinical syndromes with impaired ventricular filling or ejection ability due to any structural or functional abnormality of the heart at rest or under stress, the main clinical manifestations of which are dyspnea and fatigue (exercise tolerance limitation), and fluid retention (pulmonary congestion and peripheral edema). [0003] One of the main pathogenesis ...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61P9/04
CPCA61K38/1783A61P9/04
Inventor 卜军徐龙伟苏园园袁安彩
Owner RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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