Use of staphylococcus epidermidis h62-3 live bacterial preparation in the preparation of a medicament for the prevention or treatment of psoriasis

Abstract

The application belongs to the technical field of microorganisms and particularly relates to application of a staphylococcus epidermidis H62-3 live bacterial preparation in preparation of a medicine for preventing or treating psoriasis. Experimental results show that the staphylococcus epidermidis H62-3 live bacterial preparation improves the skin erythema and scurf symptoms of a psoriasis mouse model, significantly reduces the skin lesion thickness, and reduces the mRNA expression level of cytokines related to psoriasis at the skin lesion of the psoriasis mouse model, the cytokines including interleukin-17A, interleukin-17F and interleukin-23. Therefore, the staphylococcus epidermidis H62-3 live bacterial preparation has a prospect of being developed into a medicine for preventing or treating psoriasis.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of microbial technology, and particularly relates to application of a Staphylococcus epidermidis H62-3 live bacterial preparation in preparation of a medicine for preventing or treating psoriasis. BACKGROUND

[0002] Psoriasis is a chronic inflammatory skin disease characterized by erythema, localized scaly papules and plaques. Psoriasis can cause itching, irritation, burning and stinging, and its pathogenesis is very complex, which is considered to be the result of the combined action of genetics, epigenetics and environmental factors. The most common type of psoriasis is psoriasis vulgaris, accounting for nearly 85-90% of all psoriasis cases. Histopathologically, psoriasis is characterized by excessive proliferation and abnormal differentiation of keratinocytes, dilation of new capillaries, and inflammatory infiltration of the dermis. Clinically, psoriasis is characterized by repeated occurrence of multiple layers of silver-white dry scales, with extensive infiltrative erythema and bleeding points distributed under the scales, and can be accompanied by pruritus.

[0003] Currently, the treatment of psoriasis is mainly divided into traditional therapy and biological target therapy according to the drug type. The effect of traditional therapy can only achieve short-term clinical efficacy, and it is difficult to cure, and most of them are accompanied by varying degrees of adverse reactions. Biological target therapy has higher efficacy and better safety than traditional therapy, but some patients have poor treatment effect or adverse reactions, and in addition, some biological agents are expensive. At present, psoriasis cannot be cured, but management should aim to minimize physical and psychological harm by treating patients early in the disease process, identifying and preventing related comorbidities, changing lifestyle, and adopting individualized treatment methods. For the treatment of psoriasis patients, it is of great significance to develop new safe, efficient and economical psoriasis treatment drugs.

[0004] Bacteria, fungi and viruses colonized on the skin surface form the skin microbiome, also known as skin flora. Recent studies have shown that the skin flora of normal people interacts with the host, and a healthy skin flora is essential for maintaining skin barrier function. There is a relative balance between pathogenic bacteria and beneficial bacteria on the surface of healthy skin, and once the balance is broken, it can cause skin inflammation, itching and even disease. For example, when the sebaceous glands secrete excessively and the sebaceous glands are blocked, the microorganisms in the hair follicles, especially Propionibacterium acnes, will multiply rapidly. It secretes lipase, protease and hyaluronidase, which destroys tissues and causes infection, forming abscesses and acne, and further affecting personal appearance and life. At the same time, there are also a large number of beneficial bacteria on healthy skin. For example, Staphylococcus epidermidis, as a representative of beneficial bacteria, can secrete antibacterial peptides, decompose sebum to generate short-chain fatty acids and other metabolites, and has functions such as antibiosis, immune regulation and promotion of barrier repair.

[0005] Studies have found that patients with psoriasis have severe skin microbiota imbalance. Psoriasis-associated flora shows higher diversity and heterogeneity than healthy skin bacterial communities, and specific microbial characteristics are associated with psoriatic lesion skin, psoriatic non-lesion skin, and healthy skin. Staphylococcus aureus is more abundant in both non-lesion and lesion skin of psoriasis, while Staphylococcus epidermidis and Propionibacterium acnes have lower incidence in psoriatic lesions than in healthy skin, and Proteobacteria are overabundant in psoriatic skin. Based on the close relationship between skin flora and inflammatory skin diseases such as psoriasis, potential therapeutic probiotics for external use are selected, and drug ointments or creams containing specific probiotics are prepared to antagonize the growth of other harmful bacteria or interact with the immune system to enhance its ability to repair lesions and maintain skin health. SUMMARY

[0006] In view of the deficiencies of the prior art, the purpose of the present application is to provide a use of Staphylococcus epidermidis H62-3 live bacterial preparation in the preparation of a drug for preventing or treating psoriasis, providing a new idea for the effective treatment of psoriasis with skin external probiotic strains or external drugs.

[0007] To achieve the purpose of the present application, the following technical solutions are used:

[0008] In a first aspect, the present application provides a use of Staphylococcus epidermidis H62-3 in the preparation of a drug for preventing or treating psoriasis.

[0009] The present application first collects the skin flora of the face of healthy people at different ages, and isolates the functional Staphylococcus epidermidis strain H62-3 through culture omics. The taxonomic name of the Staphylococcus epidermidis is Staphylococcus epidermidis (Staphylococcus epidermidis) Staphylococcus epidermidis ), which was deposited with the China General Microbiological Culture Collection Center (CGMCC) on February 21, 2023, at the address of the Institute of Microbiology, Chinese Academy of Sciences, No. 1, Beichen West Road, Chaoyang District, Beijing, China, with the accession number CGMCC No. 26640. For more information, see CN116286543A.

[0010] The strain is gram-positive, with white and small colonies on TSA plates, forming smooth and opaque round protrusions. Under a microscope, it is spherical, non-motile, and does not produce spores. Its optimal growth temperature is 32-38℃, and it grows rapidly in TSB liquid medium, entering the logarithmic phase in about 2h and the stationary phase in about 12h.

[0011] In some embodiments of the present application, the Staphylococcus epidermidis H62-3 improves the symptoms of skin erythema and scaling in a psoriasis mouse model and significantly reduces lesion thickness.

[0012] In some embodiments of the present application, the Staphylococcus epidermidis H62-3 is used to reduce the expression level of the mRNA of the cytokines related to psoriasis at the damaged skin.

[0013] In some embodiments of the present application, the cytokines include interleukin-17A, interleukin-17F, and interleukin-23.

[0014] In some embodiments of the present application, the psoriasis is at least one of psoriasis vulgaris, psoriasis erythroderma, psoriasis arthropathica, or pustular psoriasis.

[0015] In a second aspect, the present application provides a use of a Staphylococcus epidermidis H62-3 live bacterial preparation in the preparation of a medicament for preventing or treating psoriasis, wherein the Staphylococcus epidermidis H62-3 live bacterial preparation is prepared from the Staphylococcus epidermidis H62-3 of the above-mentioned first aspect.

[0016] In some embodiments of the present application, the Staphylococcus epidermidis H62-3 live bacterial preparation improves the symptoms of skin erythema and scaling of the psoriasis mouse model, and significantly reduces the thickness of the skin lesions.

[0017] In some embodiments of the present application, the Staphylococcus epidermidis H62-3 live bacterial preparation is used to reduce the expression level of the mRNA of the cytokines related to psoriasis at the damaged skin.

[0018] In some embodiments of the present application, the cytokines include interleukin-17A, interleukin-17F, and interleukin-23.

[0019] In some embodiments of the present application, the psoriasis is at least one of psoriasis vulgaris, psoriasis erythroderma, psoriasis arthropathica, or pustular psoriasis.

[0020] In some embodiments of the present application, the preparation method of the Staphylococcus epidermidis H62-3 live bacterial preparation comprises the following steps: picking a single colony of the activated Staphylococcus epidermidis strain H62-3 and inoculating it into a TSB liquid medium, and placing it in a 32-38℃ shaker for 14-18h of shaking culture as a seed liquid; inoculating the seed liquid into the TSB liquid medium at a volume fraction of 3%-5% of the inoculation amount, and placing it in a 32-38℃ shaker for 14-18h of shaking culture to obtain a fermentation liquid; centrifuging the fermentation liquid, resuspending the bacterial pellet with the TSB liquid medium, and preparing a Staphylococcus epidermidis live bacterial preparation with a concentration of 1x10 9 CFU / mL.

[0021] The application firstly collects the facial skin flora of healthy people at different ages, separates single strains through culture omics, and performs efficacy strain screening and verification, so that the Staphylococcus epidermidis H62-3 live bacterial preparation can improve the symptoms such as skin erythema and scales of a psoriasis mouse model, significantly reduce the lesion thickness, and reduce the mRNA expression level of cytokines related to psoriasis at the lesion of the psoriasis mouse model, including interleukin-17A, interleukin-17F and interleukin-23, and the Staphylococcus epidermidis H62-3 live bacterial preparation has the prospect of developing into a drug for preventing or treating psoriasis.

[0022] The application has the following beneficial effects:

[0023] (1) The application provides an application of a Staphylococcus epidermidis H62-3 live bacterial preparation in the preparation of a drug for preventing or treating psoriasis, the Staphylococcus epidermidis H62-3 live bacterial preparation can improve the symptoms such as skin erythema and scales of a psoriasis mouse model, significantly reduce the lesion thickness, and reduce the mRNA expression level of cytokines related to psoriasis at the lesion of the psoriasis mouse model, including interleukin-17A, interleukin-17F and interleukin-23, and the Staphylococcus epidermidis H62-3 live bacterial preparation has the prospect of developing into a drug for preventing or treating psoriasis.

[0024] (2) The application provides an application of Staphylococcus epidermidis H62-3 in the preparation of a drug for preventing or treating psoriasis, which provides a new idea for safely and effectively treating psoriasis by using an external live bacterial treatment and a skin external probiotic strain. BRIEF DESCRIPTION OF DRAWINGS

[0025] The accompanying drawings are included to provide a further understanding of the application and are incorporated in and constitute a part of this specification, illustrate embodiments of the application and together with the description serve to explain the application, and do not limit the application. In the drawings:

[0026] Figure 1 It is the colony morphology of Staphylococcus epidermidis H62-3;

[0027] Figure 2 It is the gram staining of Staphylococcus epidermidis H62-3;

[0028] Figure 3 It is the growth curve of Staphylococcus epidermidis H62-3;

[0029] Figure 4 It is the ANI analysis result of Staphylococcus epidermidis H62-3;

[0030] Figure 5 It is the influence of Staphylococcus epidermidis H62-3 on the psoriasis lesion of C57BL / 6 mice induced by imiquimod;

[0031] Figure 6 Effect of S. epidermidis H62-3 on PASI score of psoriatic lesions in C57BL / 6 mice induced by imiquimod;

[0032] Figure 7 Effect of S. epidermidis H62-3 on pathology of psoriasis-like lesions in C57BL / 6 mice induced by imiquimod;

[0033] Figure 8 Effect of S. epidermidis H62-3 on stratum spinosum thickness of psoriatic lesions in C57BL / 6 mice induced by imiquimod;

[0034] Figure 9 Effect of S. epidermidis H62-3 on spleen index of C57BL / 6 mice induced by imiquimod;

[0035] Figure 10 Effect of S. epidermidis H62-3 on transcriptional level of psoriasis-related cytokines in psoriatic lesions of C57BL / 6 mice induced by imiquimod;

[0036] Figure 11 Effect of S. epidermidis H62-3 on Ki67 protein level in psoriatic lesions of C57BL / 6 mice induced by imiquimod. DETAILED DESCRIPTION

[0037] The scheme of the present application will be explained below in conjunction with examples. Those skilled in the art will understand that the following examples are only for illustration of the present application and should not be regarded as limiting the scope of the present application. If a specific technique or condition is not mentioned in the examples, it is performed according to the technique or condition described in the literature in the art or according to the product manual. If a reagent or instrument is not mentioned by the manufacturer, it is a conventional product that can be obtained by purchase in the market.

[0038] The bacterial culture medium used in the following examples is as follows:

[0039] Trypticase soy broth liquid medium (TSB): trypticase 17.0 g / L, soy peptone 3.0 g / L, sodium chloride 5.0 g / L, potassium phosphate dibasic 2.5 g / L, glucose 2.5 g / L, 121℃ high pressure sterilization for 15 min, ready for use.

[0040] Trypticase soy agar solid medium (TSA): trypticase 17.0 g / L, soy peptone 3.0 g / L, sodium chloride 5.0 g / L, potassium phosphate dibasic 2.5 g / L, glucose 2.5 g / L, agar powder 15 g / L, 121℃ high pressure sterilization for 15 min, pour plate, ready for use.

[0041] Example 1: This example is the isolation, screening and purification of Staphylococcus epidermidis H62-3 according to the present application

[0042] (1) Sample collection

[0043] ①Recruit volunteers with healthy facial skin at different ages (18-90 years old), and require them to have no acne, pustules, no inflammation, no erythema, etc. No oral antibiotic preparations within the past 2 months or no external use of antibiotic preparations within the past 2 weeks. The sample is taken within 12 hours without cleaning or washing the face.

[0044] ②The sampler wears a mask and disposable sterile gloves, and soaks a sterile sampling cotton swab with sterile saline. The cotton swab is 2 cm long, and the sampling site is marked with a 4 cm length. The cotton swab is wiped back and forth 50 times, which takes about 30 seconds, and the area is about 8 cm 2 . After wiping, the cotton swab is placed in a glycerol preservation tube, the lid is tightly sealed, and the number is recorded.

[0045] (2) Skin flora culture, isolation, purification and preservation

[0046] ①Take 0.05 mL of glycerol preservation solution and dilute with 0.15 mL of sterile water. Spread the above diluent on a TSA solid plate and place it in a 37°C incubator for 24 hours.

[0047] ②According to the colony characteristics of Staphylococcus epidermidis, single colonies are picked and separated by four-zone streaking, and placed in a 37°C incubator for 24 hours.

[0048] ③16S rRNA sequencing is performed to determine the single colony of Staphylococcus epidermidis preserved at -80°C.

[0049] (3) Functional bacteria screening

[0050] Extract the whole genome RNA of different strains of Staphylococcus epidermidis, reverse transcribe it into cDNA, and perform qRT-PCR experiment to screen Staphylococcus epidermidis strain H62-3 with high expression of genes closely related to moisturizing efficacy.

[0051] Example 2: This example is the microbiological identification of Staphylococcus epidermidis H62-3

[0052] (1) Colony characteristics

[0053] ①The colony morphology of the strain on TSA plate is shown in Figure 1 . The colony is small and white, forming a smooth and opaque round protrusion without hemolytic ring.

[0054] ②Gram staining is positive, as shown in Figure 2 . The bacterial body is spherical, some arranged in grape-like shape, and some arranged individually, without flagella and spores.

[0055] (2) Cultural characteristics

[0056] ① The optimum growth temperature of the strain is 32-38℃, and the optimum pH is 5.0-8.0.

[0057] ② The activated strain is inoculated into TSB liquid medium and placed in a 32-38℃ shaker for 14-18h as seed liquid; the seed liquid is inoculated into TSB liquid medium at a volume fraction of 3%-5%, and the OD value of the culture liquid is measured at 600nm every 1h in a 37℃ shaker for 24h, and the growth curve of the strain is drawn with OD600 as the vertical axis and time as the horizontal axis, as shown in Figure 3 , it can be found that Staphylococcus epidermidis H62-3 grows rapidly in TSB liquid medium, enters the logarithmic phase after about 2h, and enters the stationary phase after about 12h.

[0058] (3) Genetic characteristics

[0059] The genomic DNA of the strain H62-3 is extracted, and the sample is sequenced by Illumina Hiseq 2000 sequencing platform to obtain second-generation data and PacBio sequencing to obtain third-generation data. After quality control, Denovo assembly is performed, the spliced correction is made into a complete genome, and gene prediction is performed. The predicted gene protein is compared with each database such as NR library, and the species information of the strain is obtained, as shown in Table 1, which can determine that the strain H62-3 is Staphylococcus epidermidis.

[0060] Table 1: Sequence alignment results of Staphylococcus epidermidis H62-3

[0061]

[0062] According to the above colony, cultural, genetic and other characteristics, it is determined that the strain H62-3 is Staphylococcus epidermidis. Since the ANI of Staphylococcus epidermidis H62-3 and Staphylococcus epidermidis model strain CGMCC 1.4260 is 97.1%, as shown in Figure 4 , it can be determined that they are not the same strain. Through single nucleotide polymorphism (SNP) and insertion and deletion (InDel) analysis, it is found that Staphylococcus epidermidis H62-3 has numerous base mutations, additions or deletions, which lead to changes in proteins and affect their biological functions. The strain has been preserved in the China General Microbiological Culture Collection Center (CGMCC) on February 21, 2023, and its preservation number is CGMCC No. 26640.

[0063] Example 3: This example is an experiment of Staphylococcus epidermidis H62-3 live bacterial preparation improving psoriasis lesions induced by imiquimod in C57BL / 6 mice

[0064] Housing environment: SPF level; Mice: C57BL / 6 female mice, 7 weeks old; Modeling method: After the purchased 7-week-old C57BL / 6 female mice of uniform size were stably fed for one week, the back was depilated 2 cm x 2 cm, and randomly divided into 4 groups, 5 in each group. Each mouse was evenly smeared with 62.5 mg imiquimod on the back every morning for 6 consecutive days. Four treatment methods were set up, with 5 biological replicates for each treatment method. The administration treatment was unified on the modeling day, local administration, modeling every morning, administration 12 hours later, and the treatment methods were as follows:

[0065] ① Treatment 1 (control), normal control mice, without any treatment;

[0066] ② Treatment 2 (imiquimod), 62.5 mg imiquimod was evenly smeared on the back of each mouse every morning, and 12 hours later, the blank matrix of the live bacteria preparation for external use was given, for 6 consecutive days, which was the psoriasis model group;

[0067] ③ Treatment 3 (calcipotriol), 62.5 mg imiquimod was evenly smeared on the back of each mouse every morning, and 12 hours later, 12 mg / 4 cm of calcipotriol ointment for external use was given, for 6 consecutive days, which was the positive control group; 2

[0068] ④ Treatment 4 (H62-3), 62.5 mg imiquimod was evenly smeared on the back of each mouse every morning, and 12 hours later, 2 x 10 8 CFU / 4 cm 2 of Staphylococcus epidermidis H62-3 live bacteria preparation for external use was given, for 6 consecutive days, which was the experimental group.

[0069] The mice in each group were photographed every other day and the PASI score of psoriasis lesions was performed, and on the 7th day, the mice were sacrificed, and the back lesions were taken, and the mouse lesions and pathological HE staining were analyzed. As shown in Figure 5 compared with the normal control mice, imiquimod induced typical psoriasis lesions, which manifested as thickening of the mouse back skin, appearance of erythema and scales. Compared with the psoriasis model mice, the group of external use of Staphylococcus epidermidis H62-3 live bacteria preparation improved the erythema, scales and skin thickening, and the curative effect was equivalent to that of the calcipotriol positive control group, but the mouse body weight of the calcipotriol positive control group was generally reduced, and the side effects were obvious. Therefore, the external use of Staphylococcus epidermidis H62-3 live bacteria preparation for treating psoriasis is a new safe and low-toxicity therapy.

[0070] Example 4: This example is an experiment of Staphylococcus epidermidis H62-3 live bacteria preparation improving the PASI score of imiquimod-induced C57BL / 6 mouse psoriasis lesions

[0071] ​The erythema, scaling and thickening of the back skin lesions were scored according to the mice sacrificed in Example 3. The severity of the back skin lesions was evaluated according to the Psoriasis Area and Severity Index (PASI) scoring system (see Table 2) which assesses the severity of skin lesions including erythema, scaling and thickness of the infiltrate. Each parameter was scored independently on a scale of 0 to 4, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = obvious symptoms, 4 = very obvious symptoms, as shown in Table 2, and the cumulative score represents the statistical results of the severity of the disease. Compared with the normal control mice, the mice developed obvious erythema, scaling and skin thickening after continuous application of imiquimod for 6 days, and the calcipotriol positive control group and the live Staphylococcus epidermidis H62-3 preparation group significantly alleviated the imiquimod-induced erythema, scaling and skin thickening of the back, as shown in Figure 6 .

[0072] Table 2: Details of Psoriasis-like Dermatitis Severity (PASI) Scoring in Mice

[0073]

[0074] Example 5: This example is an experiment for improving imiquimod-induced psoriasis skin lesions in C57BL / 6 mice by live Staphylococcus epidermidis H62-3 preparation

[0075] The skin lesions of the mice sacrificed in Example 3 were subjected to HE staining, and the typical pathological results are shown in Figure 7 . Compared with the normal control mice, the mice developed obvious erythema, scaling and skin thickening after continuous application of imiquimod for 6 days, and the calcipotriol positive control group and the live Staphylococcus epidermidis H62-3 preparation group significantly alleviated the imiquimod-induced erythema, scaling and skin thickening of the back, as shown in Figure 7 .

[0076] Example 6: This example is an experiment for improving imiquimod-induced psoriasis skin lesions in C57BL / 6 mice by live Staphylococcus epidermidis H62-3 preparation

[0077] The mouse skin lesions in Example 3 were taken for HE staining, observed under a microscope and scanned for photography, and histopathological analysis was performed, and the index of stratum spinosum hypertrophy and dermal inflammatory cell infiltration was quantified. The quantification method of stratum spinosum hypertrophy is to select a field of view under the scanning graph of HE staining under a microscope, fix the magnification (x20), and select all epidermis regions in the field of view using Adobe Photoshop 2023 software under the field of view, and the pixel area of the epidermis region is obtained, and the stratum spinosum hypertrophy degree = epidermis pixel / total pixel of the field of view. The quantification method of dermal inflammatory cell infiltration is to select a field of view under the scanning graph of HE staining, fix the magnification (x20), and randomly select 5 non-overlapping square regions (fixed side length of 1 unit) in the dermis region under the field of view using Adobe Photoshop 2023 software, and use the counting tool to calculate the number of inflammatory cells in each region, then the dermal inflammatory cell infiltration = average unit area inflammatory cell count. Compared with the normal control mice, after continuous application of imiquimod for 6 days, the stratum spinosum hypertrophy and dermal inflammatory cell infiltration of the model group mice can be effectively relieved by the calcipotriol positive control group and the Staphylococcus epidermidis H62-3 live bacterial preparation group, as shown in Figure 8 .

[0078] Example 7: This example is a Staphylococcus epidermidis H62-3 live bacterial preparation experiment for improving the spleen index of C57BL / 6 mice with psoriasis induced by imiquimod

[0079] The spleen of the mouse killed in Example 3 was taken, and the mouse body weight and spleen size were statistically analyzed. Compared with the normal control mice, after continuous application of imiquimod for 6 days, the mouse spleen index was significantly increased, and the calcipotriol positive control group and the Staphylococcus epidermidis H62-3 live bacterial preparation group can slightly relieve the increase of the mouse spleen index induced by imiquimod, as shown in Figure 9 .

[0080] Example 8: This example is a Staphylococcus epidermidis H62-3 live bacterial preparation experiment for improving the transcription level expression of cytokines related to psoriasis lesions in C57BL / 6 mice with psoriasis induced by imiquimod

[0081] The skin lesion tissues of the mice killed in Example 3 were taken, and total RNA was extracted by using the Trizol method, and then the total RNA was reversely transcribed into cDNA, and then qPCR was performed to detect the expression of three kinds of inflammatory factor genes. Compared with the normal control mice, after being continuously smeared with imiquimod for 6 days, the mice can be induced to have psoriasis-like dermatitis, which is related to the release of cytokines and cell infiltration in the skin lesion tissues. Compared with the normal control mice, the content of the cytokines IL-17A, IL-17F and IL-23 related to psoriasis in the skin lesion tissues of the mice in the imiquimod modeling group is significantly increased, and the positive control group of calcipotriol and the live bacterial preparation group of Staphylococcus epidermidis H62-3 can reduce the transcription level of the above-mentioned cytokines to different degrees, as shown in Table 1. Figure 10 As shown in Table 1, the inhibition rates of IL-17A, IL-17F and IL-23 in the positive control group of calcipotriol can reach 70.8%, 67.5% and 67.2% respectively after local administration. The inhibition rates of IL-17A, IL-17F and IL-23 in the live bacterial preparation group of Staphylococcus epidermidis H62-3 can reach 55.9%, 55.0% and 53.2% respectively after local administration.

[0082] Example 9: This example is an experiment for improving the expression level of Ki67 protein in the psoriasis skin lesion of C57BL / 6 mice induced by imiquimod by using the live bacterial preparation of Staphylococcus epidermidis H62-3

[0083] The skin lesion of the mice killed in Example 3 was taken, fixed, paraffin-embedded, sliced, and then subjected to Ki67 immunohistochemical staining, and then observed and scanned under a microscope and photographed. Compared with the normal control mice, the expression level of Ki67 in the skin lesion tissues of the mice in the imiquimod modeling group is significantly increased, and the positive control group of calcipotriol and the live bacterial preparation group of Staphylococcus epidermidis H62-3 can effectively reduce the expression level of Ki67, as shown in Table 2. Figure 11

[0084] The application provides an application of the live bacterial preparation of Staphylococcus epidermidis H62-3 in the preparation of a medicine for treating psoriasis. The live bacterial preparation of Staphylococcus epidermidis H62-3 can improve the symptoms such as skin erythema and scales of a psoriasis mouse model, significantly reduce the thickness of a skin lesion, and reduce the expression level of the mRNA of cytokines related to psoriasis in the skin lesion of a psoriasis mouse model, and the inflammatory factors include interleukin-17A, interleukin-17F and interleukin-23. The live bacterial preparation of Staphylococcus epidermidis H62-3 has the prospect of being developed into a medicine for treating psoriasis. The application provides an application of the live bacterial preparation of Staphylococcus epidermidis H62-3 in the preparation of a medicine for treating psoriasis, and provides a new idea for treating psoriasis by using an external live bacterium and safely and effectively treating psoriasis by using an external probiotic strain.

[0085] ​Although the embodiments of the present application have been shown and described above, it is understood that the above-described embodiments are exemplary and are not to be construed as limiting the present application, and that variations, modifications, substitutions and changes can be made by those skilled in the art without departing from the scope of the present application.

Claims

1. A Staphylococcus epidermidis H62 3. The use of live bacteria in the preparation of drugs for the prevention or treatment of psoriasis, wherein the Staphylococcus epidermidis H62 3. To reduce the expression levels of psoriasis-associated cytokine mRNAs in damaged skin, said cytokines including interleukins. 17A, Interleukin 17F, interleukin 23. The psoriasis mentioned is psoriasis vulgaris.

2. The Staphylococcus epidermidis H62 as described in claim 1 3. Its application in the preparation of drugs for the prevention or treatment of psoriasis, characterized in that, Staphylococcus epidermidis H62 3. Improved skin erythema and scaling symptoms in a mouse model of psoriasis and significantly reduced skin lesion thickness.

3. A Staphylococcus epidermidis H62 strain 3. The application of live bacterial preparations in the preparation of drugs for the prevention or treatment of psoriasis, characterized in that, Staphylococcus epidermidis H62 3. The live bacterial preparation is made from Staphylococcus epidermidis H62 as described in claim 1.

3. The prepared Staphylococcus epidermidis H62 was obtained.

3. Live bacterial preparations are used to reduce the expression levels of psoriasis-associated cytokine mRNAs in damaged skin, including interleukins. 17A, Interleukin 17F, interleukin 23; The psoriasis mentioned is psoriasis vulgaris.

4. Staphylococcus epidermidis H62 as described in claim 3 3. The application of live bacterial preparations in the preparation of drugs for the prevention or treatment of psoriasis, characterized in that, Staphylococcus epidermidis H62 3. Live bacterial preparations improved skin erythema and scaling symptoms in a mouse model of psoriasis and significantly reduced the thickness of skin lesions.

5. As claimed in claim 3 4. Staphylococcus epidermidis H62 as described in any one of claims 3. The application of live bacterial preparations in the preparation of drugs for the prevention or treatment of psoriasis, characterized in that, Staphylococcus epidermidis H62 3. The preparation method of live bacterial preparation includes the following steps: activating Staphylococcus epidermidis strain H62...

3. Pick a single colony and inoculate it into TSB liquid medium, then incubate at 32°C. Cultured in a shaker at 38°C for 14 days. 18h, as seed solution; with a volume fraction of 3% A 5% inoculum was inoculated into TSB liquid medium, and 32 Cultured in a shaker at 38°C for 14 days After 18 hours, the fermentation broth was obtained; the fermentation broth was centrifuged, and the bacterial precipitate was resuspended in TSB liquid medium to prepare 1×10⁻⁶ cells / mL. 9 CFU / mL live Staphylococcus epidermidis preparation.

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