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Application of iron sucrose to preparation of drug for treating angiosteosis induced by hyperphosphatemia

A technology for hyperphosphatemia and vascular calcification, which is applied in the application field of vascular calcification drugs, can solve the problems of lack of prevention and treatment methods for vascular calcification, and achieve the effects of improving the quality of life, reducing the incidence rate, and reducing the cost

Active Publication Date: 2020-10-16
荆门市第一人民医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is also a lack of effective prevention and treatment methods for vascular calcification induced by hyperphosphatemia.

Method used

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  • Application of iron sucrose to preparation of drug for treating angiosteosis induced by hyperphosphatemia
  • Application of iron sucrose to preparation of drug for treating angiosteosis induced by hyperphosphatemia
  • Application of iron sucrose to preparation of drug for treating angiosteosis induced by hyperphosphatemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Male SD (Sprague-Dawley) rats were adaptively fed for 1 week and then euthanized. The aortic rings were taken and placed in each experimental group for 14 days. The grouping situation is: CNT, normal control group (conventional medium); HP, high phosphorus group (conventional medium + 2.5mM PO 4 3- ); HPLFe, high phosphorus and low iron group (conventional medium + 2.5mM PO 4 3- +2μg / ml iron sucrose); HPMFe, high phosphorus medium iron group (conventional medium +2.5mM PO 4 3- +5μg / ml iron sucrose); HPHFe, high phosphorus and high iron group (conventional medium +2.5mMPO 4 3- +10 μg / ml iron sucrose).

[0033] Among them, the composition of conventional medium is: conventional DMEM medium (dulbecco's modified eagle medium) + 10% FBS (fetal bovine serum) + 1% double antibody (penicillin and streptomycin mixture).

[0034] The vascular rings of each experimental group were stained for calcium (Von Kossa staining) and iron (Perls' Prussianblue staining), and the calc...

Embodiment 2

[0052] The vascular rings of each experimental group in Example 1 were stained with reactive oxygen species (ROS) fluorescent probe DHE, MDA and SOD were detected.

[0053] DHE staining steps:

[0054] 1. Dissolve DHE (Dihydroethidium) in DMSO (Dimethyl sulfoxide) to a 5 mM solution, and store it away from light for later use.

[0055] 2. Dilute the solution at a ratio of 1:1000 before use.

[0056] 3. After the animals were sacrificed, the blood vessel rings were taken out, washed with PBS, and frozen.

[0057] 4. Section the frozen vascular ring with a cryostat.

[0058] 5. After making slices, add the diluted probe solution to the tissue dropwise. Incubate at 37°C for 30min.

[0059] 6. Wash off the excess probe solution with PBS, and seal the slide with anti-fluorescence quenching agent.

[0060] 7. Observe and take pictures with a fluorescent microscope.

[0061] Test results such as figure 2 as shown, figure 2 Content A is the staining of vascular ring ROS (rea...

Embodiment 3

[0066] RT-qPCR method was used to detect the gene expressions of ɑ-SMA, Runx2, Pit1 and FGF23 in the vascular rings of each experimental group in Example 1; the protein expressions of ɑ-SMA, Runx2, Pit1 and FGF23 were detected by Western blot method to investigate different concentrations The effect of iron sucrose on the phenotypic transformation of vascular smooth muscle cells stimulated by high phosphorus, the results are as follows image 3 shown.

[0067] image 3 Content A is the gene expression (RT-qPCR) of α-SMA, Runx2, Pit1 and FGF23 in the vascular ring of each experimental group; content B and Figure 4 Protein expression of α-SMA, Runx2, Pit1 and FGF23 in vascular ring (Western blot). ɑ-SMA is ɑ-smooth muscle actin, the lower the value, the more obvious the phenotypic transformation; Runx2 is Runt-related transcription factor 2, the higher the phenotype transformation is; Pit1 is the type III sodium-phosphate symporter 1, The higher it is, the more obvious the p...

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Abstract

The invention belongs to the technical field of angiosteosis treatment and particularly relates to an application of iron sucrose to preparation of a drug for treating angiosteosis induced by hyperphosphatemia. Hyperphosphatemia causes an oxidative stress injury in a vascular smooth muscle cell to induce phenotypic transformation from the vascular smooth muscle cell into an osteoblast and to finally develop into angiosteosis. In experiments of the invention, it is found that the iron sucrose can interfere with the transmembrane transport of inorganic phosphorus in blood, inhibit the expressionof a phosphorus transmembrane transporter and antagonize the oxidative stress injury induced by the hyperphosphatemia, so as to play a role in treating, relieving or inhibiting the angiosteosis induced by the hyperphosphatemia.

Description

technical field [0001] The invention belongs to the technical field of vascular calcification treatment, and more specifically relates to the application of iron sucrose in the preparation of medicaments for treating vascular calcification induced by hyperphosphatemia. Background technique [0002] Vascular calcification is mainly manifested as increased stiffness of the vessel wall, decreased compliance, and brittle and thinner vessel walls, making vessels easily ruptured. Vascular calcification has a high incidence and great harm in patients with chronic kidney disease. However, the pathogenesis of vascular calcification has not been fully elucidated, and there is still a lack of effective prevention and treatment methods in clinical practice. [0003] Hyperphosphatemia is a common complication in patients with chronic kidney disease and an important cause of vascular calcification. Hyperphosphatemia induces oxidative stress damage in vascular smooth muscle cells, which i...

Claims

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Application Information

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IPC IPC(8): A61K33/26A61K31/7016A61P9/14A61P3/12A61P39/06
CPCA61K33/26A61K31/7016A61K9/0019A61P9/14A61P3/12A61P39/06A61K2300/00
Inventor 汪平彭丹杨举红胡宁任慧敏郭成坤全正莉宋艳潘慧陈望善
Owner 荆门市第一人民医院
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