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Pharmaceutical composition containing miRNA-873 and application thereof

A technology of miRNA-873 and composition, applied in the field of biopharmaceuticals, to achieve the effect of improving injury, improving heart function, and resisting myocardial ischemia-reperfusion injury

Inactive Publication Date: 2016-01-27
QINGDAO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the signaling pathway of cardiomyocyte necrosis is still far from elucidated, and the pathway of miRNA in regulating the process of cardiomyocyte necrosis needs further study. Therefore, it is necessary to search for miRNAs that are specifically expressed in the heart and participate in cardiomyocyte necrosis, and to elucidate their mechanism of action. The diagnosis and treatment of heart disease based on miRNA has great significance and application prospects

Method used

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  • Pharmaceutical composition containing miRNA-873 and application thereof
  • Pharmaceutical composition containing miRNA-873 and application thereof
  • Pharmaceutical composition containing miRNA-873 and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Embodiment 1: myocardial ischemia and H 2 o 2 Detection of miRNA-873 expression during induced cardiomyocyte necrosis

[0016] This embodiment uses the experimental model of myocardial cell necrosis, and adopts the method established in this laboratory to cultivate the primary cardiomyocytes of rat suckling mice (rat suckling mice were purchased from Beijing Medical University, the rat strain is Wistar rats, rat suckling mice The preparation of primary cardiomyocytes can be found in the following documents: W.-Q.Tan, et al, Foxo3aInhibitsCardiomyocyteHypertrophythroughTransactivatingCatalaseJBiolChem.2008October31; 283(44):29730-29739), 500uMH 2 o 2 Treat different times, extract RNA, and detect the expression level of miRNA-873 by real-time fluorescent quantitative PCR technology, such as figure 1 As shown in A, the expression level of miRNA-873 in H 2 o 2 Significantly down-regulated within 8h to 12h of induction.

[0017] In this embodiment, the rats treated wi...

Embodiment 2

[0018] Example 2: Experiment of miRNA-873 inhibiting cardiomyocyte apoptosis

[0019] In this example, primary cultured cardiomyocytes were used as a model. Transfect miRNA-873 pharmaceutical composition, miRNA-873 random sequence is used as control (ie NC), after 24 hours, use H 2 o 2 The cells were induced and treated for 12 hours, and the necrosis of cardiomyocytes was detected; the death of cardiomyocytes was detected by PI staining, and the results showed that overexpression of miRNA-873 could significantly inhibit H 2 o 2 induced cardiomyocyte apoptosis.

Embodiment 3

[0020] Example 3: Experimental verification of miRNA-873 overexpression inhibiting myocardial ischemia injury

[0021]Injection of the miRNA-873 pharmaceutical composition into the mice designed in this example can significantly inhibit myocardial ischemia-reperfusion injury. Taking C57 mice as the experimental subjects, the miRNA-873 pharmaceutical composition and miRNA-873 drug were injected according to the following method Composition negative control (NC), sham-operated mice were used as the control group, and C57 mice were used as the wild type. The mice were weighed and anesthetized, fixed in the supine position, sheared and disinfected with iodine; the trachea was cut midline in the neck and intubated, and the animal ventilator was used for positive pressure ventilation. Open the skin about 3 cm, bluntly separate the subcutaneous tissue and muscles layer by layer, open the chest, carefully lift the pericardium and cut it open to fully expose the heart; put 200 μL of th...

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Abstract

The invention belongs to the technical field of bio-pharmaceuticals and relates to a pharmaceutical composition containing miRNA-873 and application thereof. In a milliliter of the pharmaceutical composition containing miRNA-873, the content of 1,2-dioleoyl-3-trimethylaminepropane is 0.5-25mg, the molar ratio of miRNA-873 to 1,2-dioleoyl-3-trimethylaminepropane is 1:(150-205), the content of DC cholesterol is 0.1-5mg, the content of 1,2-dioleoyl-3-phosphatidyl ethanolamine is 0.1-20mg, the content of polyethylene glycol 2000 is 1-80mg, and the pharmaceutical composition also comprises the balance of phosphate buffer. The pharmaceutical composition is used for treating heart diseases such as myocardial infarction, myocardial ischemial injury, cardiac hypertrophy or myocardial fibrosis; and moreover, the pharmaceutical composition is simple in preparation process, obvious in drug effect, convenient to use and friendly in treatment environment.

Description

Technical field: [0001] The invention belongs to the technical field of biopharmaceuticals, and relates to a new drug of endogenous non-coding small RNA and its application, especially a pharmaceutical composition containing miRNA-873 and its application for preventing or treating heart disease. Background technique: [0002] Cardiovascular disease is a major threat to human health and life, and is the number one killer of human health. Worldwide, more than 17 million people die from cardiovascular disease every year, and its mortality rate is close to the sum of all cancer mortality rates; With the improvement of people's living standards and the change of diet structure, the mortality rate of cardiovascular diseases is on the rise, surpassing cancer as the number one cause of death. According to the latest statistical results recently released by the Ministry of Health, the prevalence of hypertension among residents aged 18 and over in my country is 18.8%, and it is estima...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61P9/10A61P9/00
Inventor 王昆周露玙李培峰
Owner QINGDAO UNIV
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