Application of M2 pyruvate kinase as drug target in preparation of drugs for prevention and treatment of psoriasis

A technology of pyruvate kinase and psoriasis, applied in the field of medicine, can solve the problems of poor treatment effect and large side effects

Inactive Publication Date: 2018-10-16
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The present invention aims to solve the above-mentioned problems of large side effects and poor therapeutic effect of existing drugs for treatin

Method used

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  • Application of M2 pyruvate kinase as drug target in preparation of drugs for prevention and treatment of psoriasis
  • Application of M2 pyruvate kinase as drug target in preparation of drugs for prevention and treatment of psoriasis
  • Application of M2 pyruvate kinase as drug target in preparation of drugs for prevention and treatment of psoriasis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Detection of PKM2 in normal skin tissue and psoriatic skin lesions.

[0025] The detection method comprises the following steps:

[0026] In step S1-1, the normal skin tissue and the psoriasis lesion tissue are thoroughly rinsed with saline, and then fixed with 4% paraformaldehyde solution by volume.

[0027] Step S1-2, routine preparation and immunohistochemical staining of fixed normal skin tissue and psoriatic lesion tissue: that is, rinsing, dehydration, clearing, paraffin immersion and embedding of the fixed tissue block , with a slice width of 5 μm. After the sections were dewaxed to water, the antigen was retrieved by microwave treatment with sodium citrate buffer, washed twice with phosphate buffer, and then blocked with normal goat serum for 15 minutes. Then drop the primary antibody (PKM2 antibody, Cell Signaling Technology Company, product number 4053, use the primary antibody diluent (Beiyuntian) to dilute, the dilution ratio is 1:100; PKM1 antibody, produ...

Embodiment 2

[0036]Detection of PKM2 in normal mouse skin tissues and imiquimod mouse skin lesions.

[0037] The detection method comprises the following steps:

[0038] Step S2-1, the back of the female Balb / c mouse was shaved, and the hair was depilated with Veet depilatory cream, and then the topical drug imiquimod (Adara, 3M Health Care Limited) was applied to the skin preparation area at a dosage of 62.5mg / The imiquimod psoriasis model was prepared by applying the drug continuously for 5 days, and the imiquimod psoriasis mice were obtained. The skin preparation area of ​​normal mice was smeared with petroleum jelly at a dosage of 62.5 mg / mouse for 5 consecutive days.

[0039] In step S2-2, the same steps 1 to 7 as in Example 1 were used to detect the expression levels of PKM1 and PKM2 in normal mouse skin tissue and imiquimod mouse skin lesion tissue.

[0040] figure 2 It is the comparison chart of immunohistochemistry and western blot of PKM2 and PKM1 in the skin tissues of imiq...

Embodiment 3

[0043] Use of 1-piperidine dithiocarboxylate (1,4-dihydro-3-methyl-1,4-dioxo-2-naphthyl)methyl ester, a PKM2-specific inhibitor Mott-induced murine psoriasis for treatment.

[0044] The treatment method includes the following steps:

[0045] Step S3-1, take 18 female BALB / c mice aged 6-8 weeks (Shanghai Xipuer-Bikay Experimental Animal Co., Ltd.) and divide them into three groups, 6 in each group, respectively blank control group, model group and With PKM2 inhibitor (Compound 3k, 1-piperidine dithiocarboxylate (1,4-dihydro-3-methyl-1,4-dioxo-2-naphthyl) methyl ester, CAS: 94164- 88-2 Shanghai Chaolan Chemical Technology Center) model + PKM2 inhibitor group after treatment of the model group. After 18 mice were anesthetized, their backs were shaved. The shaved area was 2cm*3cm, and then the hair in the corresponding area was removed with Veet depilatory cream.

[0046] Step S3-2, use the method of step 1 in Example 2 to induce psoriasis in mice by topical application of imiq...

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Abstract

Disclosed is an application of M2 pyruvate kinase as drug target in the preparation of drugs for prevention and treatment of psoriasis.

Description

technical field [0001] The invention belongs to the field of medicine. Background technique [0002] Psoriasis is an inflammatory proliferative skin disease with a genetic predisposition, and its histopathological features are mainly acanthosis of the epidermis with parakeratosis, and telangiectasia in the dermis with lymphocyte infiltration. According to the data of the World Health Organization, there are at least 100 million psoriasis patients worldwide, and there are about 5-8 million patients in China. Psoriasis is easy to relapse and difficult to cure, which greatly reduces the quality of life of patients and brings a heavy economic burden to the society. The pathogenesis of psoriasis is not yet clear, currently it is believed that the excessive proliferation of epidermal cells, excessive inflammation and neovascularization are three important links in the pathogenesis of psoriasis. At present, the treatment of psoriasis can only alleviate the clinical symptoms, and ...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/4453A61P17/06
Inventor 刘韵资陈基快朱江波蒋春雷
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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