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Application of lovastatin in preparing medicament for restraining apoptosis of mesenchymal stem cell between medullas

A technology of bone marrow mesenchyme and lovastatin, which is applied in the direction of drug combinations, pharmaceutical formulas, and medical preparations containing active ingredients, etc., and can solve problems such as low survival rate and poor therapeutic effect

Inactive Publication Date: 2008-02-27
FUWAI HOSPITAL OF CARDIOVASCULAR DESEASE CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The purpose of the present invention is to provide a medicine that can improve the survival rate of bone marrow mesenchymal stem cell transplantation and improve its therapeutic effect against the shortcomings of low survival rate and poor therapeutic effect of bone marrow mesenchymal stem cell transplantation

Method used

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  • Application of lovastatin in preparing medicament for restraining apoptosis of mesenchymal stem cell between medullas
  • Application of lovastatin in preparing medicament for restraining apoptosis of mesenchymal stem cell between medullas
  • Application of lovastatin in preparing medicament for restraining apoptosis of mesenchymal stem cell between medullas

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1. In vitro test of lovastatin inhibiting bone marrow mesenchymal stem cell apoptosis

[0040] (1), MSCs isolation and culture

[0041] Sprague-Dawley rats, male or female, were taken, anesthetized intraperitoneally with ketamine hydrochloride (80 mg / kg), soaked in 75% alcohol for 3-5 minutes for disinfection. Cut the rat femur and tibia in the ultra-clean bench, rinse the bone marrow cavity several times with complete medium (IMDM+15% FBS), repeatedly suck and blow the bone marrow with a micropipette, form a dispersed single-cell suspension, and inoculate it in a culture bottle in 37°C, 5% CO 2 Cell culture incubator. After 4 to 5 days, the cells can grow to more than 80% confluence, and are passaged at a ratio of 1:3 (0.25% trypsin+0.04% EDTA). Take the well-grown first-generation cells for experiments.

[0042] (2), experimental grouping and processing

[0043] Normal control group: cultured with complete medium (IMDM+15%FBS); apoptosis model group: trea...

Embodiment 2

[0048] Example 2. Detection of apoptosis rate of bone marrow mesenchymal stem cells and changes in mitochondrial membrane potential by flow cytometry

[0049] Example 1 (2) After drug treatment of each group of cells, according to the instructions of the Annexin V / PI apoptosis detection kit, the cells of each group were digested with trypsin, then washed twice with cold PBS, incubated with Annexin V solution for 30 minutes at room temperature, and then added The PI solution was incubated for 5 minutes, and then flow cytometry was used to detect the apoptosis rate. Annexin-V / PI flow cytometry can distinguish between early apoptosis and late apoptosis. In the early stage of apoptosis, the PS on the cell membrane is everted to the outer layer of the cell membrane, showing Annexin-V positive, but the cell membrane is intact, and PI is negative; in the middle and late stage of apoptosis, the cell membrane ruptures, PI enters the cell, and the DNA binding, showing PI positive. Com...

Embodiment 3

[0050] Embodiment 3, upper flow cytometer detection mitochondrial membrane potential level experiment

[0051] Each group of cells treated according to Example 1 (2) was incubated with 0.1 μM Rhodamine 123 at 37° C. for 30 minutes, and the mitochondrial membrane potential level was detected by flow cytometry. Compared with the apoptosis model group, the mitochondrial membrane potential of the lovastatin (0.01 μM, 0.1 μM, 1 μM.) treatment group cells (see Figure 5 and Figure 6) was significantly increased, indicating that lovastatin inhibits mitochondrial apoptosis (Note: ΔΨm in Figure 5 and Figure 6 represents the mitochondrial membrane potential; where control represents the normal control group, Hypoxia / SD represents the apoptosis model group, Hypoxia / SD+0.01μM, Hypoxia / SD+0.1μM and Hypoxia / SD+1μM represent Luo Vastatin concentration treatment group).

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Abstract

The invention discloses a new application of Luovastatin, in particular to an application to prepare the drug to inhibit stem cell death among bone marrow, which is characterized by the following: treating ischemic heart disease and other limb ischemic disease; accelerating the existence of cell; improving the treating effect of the transplanted stem cell.

Description

technical field [0001] The invention relates to a drug lovastatin, in particular to a new application of lovastatin. Background technique [0002] Lovastatin (English name: Lovastatin) is an HMG-CoA reductase inhibitor, is an effective drug for the treatment of hyperlipidemia, can reduce the level of total cholesterol and LDL in serum, and is widely used in the treatment of abnormal lipid metabolism and Atherosclerosis (Calabro et al.. Curr Opin Cardiol. 2005;20:541-6). The chemical name of lovastatin is: (S)-2-methylbutanoic acid-(1S,3S,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-3,7- Dimethyl-8-[2-[(2R,4R)-4-hydroxy-6-oxo-2-tetrahydropyranyl]-ethyl]-1-naphthyl ester [0003] Its structural formula is: [0004] [0005] The molecular formula is: C 24 h 36 o 5 Molecular weight: 404.55 [0006] In addition to lipid-lowering effects, statins also have many non-lipid-lowering effects and play a key role in the prevention and treatment of cardiovascular diseases, including impro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/366A61P9/10
Inventor 徐瑞霞陈曦
Owner FUWAI HOSPITAL OF CARDIOVASCULAR DESEASE CHINESE ACAD OF MEDICAL SCI
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