CN109839507A - A kind of biomarker detecting ultraviolet light injury and its application - Google Patents
A kind of biomarker detecting ultraviolet light injury and its application Download PDFInfo
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Abstract
The present invention provides a kind of Novel marker Keratin 1s or its degradation product for diagnosing or detecting ultraviolet damage, wherein when cell or tissue is after ultraviolet light, content, the structure of Keratin 1 or its degradation product in tissue can change, and this variation is positively correlated with tissue damage.The present invention also provides another diagnosis or the methods for detecting ultraviolet damage, calculate or predict skin injury degree by the change rate of Keratin 1 or its degradation product before and after comparison tissue damage.
Description
Technical field
The present invention relates to the biomarkers for predicting and detecting UV light-induced skin injury, specifically based on detection skin
Middle Keratin 1 content and structure of variation, the detection side as the biomarker for predicting and detecting UV light-induced skin injury
Method and its application.
Background technique
Ultraviolet light in sunlight is the main reason for skin of people is damaged by ultraviolet radiation, and ultraviolet radiation is for skin
Skin can generate a variety of pathological effects, such as red swelling of the skin, decortication, inflammation, fester and a variety of skin diseases etc., and can generate
A large amount of activating oxides cause the DNA damage of subcutaneous cell, accelerate skin aging.In fact, the original of human skin aging 90%
Because being since ultraviolet light irradiates, and the disease of the most serious of ultraviolet induction is cutaneum carcinoma, and existing research proves, 90% or more
Cutaneum carcinoma be as in sunlight ultraviolet light irradiation caused by.40% in cutaneum carcinoma patient Zhan Suoyou cancer patient, the whole world
There are more than 300 Wan Xinfa skin cancer cases every year, and Skin Cancer Foundation also indicates that, 1/5th American is in life certain
A stage can obtain cutaneum carcinoma.With the progress of human industryization, it is responsible for that the ozone layer of ultraviolet light is stopped constantly to become in atmosphere
It is thin, there is expert once to predict, ozone thickness reduces 1%, and ultraviolet radiation intensity increases by 2%.Therefore, line loss ultraviolet for skin
The detection of wound improves people the generation of the general level of the health of skin, the great skin disease such as prevent cutaneum carcinoma, suffers from great
Social and economic significance and clinical value.
And in China, since population pressure is huge, diagnosis and difficulty of seeing a doctor, ultraviolet skin injury is not yet received enough heavy
Depending on often many skins are wound patient only by just Office visits after especially strong skin lesion, and make in recent years, and China is
Gradually increase as skin disease caused by the ultraviolet wound in the whole world and cutaneum carcinoma patient populations.Therefore, the ultraviolet damage of effective skin
The detection method and means of wound, and the portable ultraviolet damage detection device of low cost, monitoring, skin for skin health
The diagnosing and treating of disease especially cutaneum carcinoma is significant.
Based on clinically the diagnosis of skin ultraviolet injury is estimated with dermatologist now, to the experience dependence of doctor
By force, and more serious skin injury can only be assessed, cannot achieve the accumulation property skin injury caused by ultraviolet light, especially
It is the early diagnosis of skin canceration.Existing skin injury detecting instrument, can only be by ultraviolet light during organizational communication
Difference is absorbed, a very "ball-park" estimate is realized to the subcutaneous catoptric imaging that carries out.Its principle is: ultraviolet light irradiation skin, inspection
The light that skin reflex is returned is surveyed, since the absorption coefficient of normal skin tissue and affected area to light is different, by reflection or is dissipated
It is emitted back towards the light come to be imaged, does one so as to the content to melanin in skin, moisture, lipid and very rough estimate
Meter.Since the propagation of laser in the tissue is very sensitive for scattering, and according to Rayleigh scattering and more scattering principle, photon is scattered
The biquadratic of the amount of penetrating and wavelength is inversely proportional, for ultrashort wavelength this for ultraviolet light, skin histology propagation by dissipate
The interference penetrated highly significant, while absorption of the ultraviolet light in normal cell is also strongly, therefore, this catoptric imaging
It will receive very multifactor interference, accuracy rate and repeatability are all very low.Personally for same one, in different tissues,
Or the measurement under the different muscular states in same tissue, the result difference that may be measured with it is ultraviolet it is impaired caused by difference
Quite.Therefore, this quasi-instrument clarity, poor sensitivity, can not detect early stage skin injury caused by ultraviolet light, to skin injury
And further the early detection of skin disease and prevention have no directive significance, clinically almost without application.Particularly, right
In Dermatology Outpatient Department, often light experiment can only be used to do a qualitative evaluation to the ultraviolet-sensitive of skin, method is, one
A non-light-exposed skin area, as back one piece of skin on carry out ultraviolet light, then by this block skin occur erythema
Area evaluates the skin ultraviolet-sensitive of patient, both inaccurate, the direct detection that can not be also damaged.
Summary of the invention
The present invention provides a kind of molecular marked compound in preparation for diagnosing and predicting ultraviolet induction cell and tissue damage
The reagent of wound or the application in kit, wherein the molecular marked compound includes Keratin 1.
In the present invention, the detection of the Keratin 1 is including in gene level, protein level, protein structure variation
It is one or more.Wherein, Keratin 1 is preferably the Keratin 1 segment of lack part amino acid sequence, and also referred to as Keratin 1 drops
Solve object；Keratin 1 can be the blend compositions of above-mentioned segment albumen and overall length Keratin 1, detect above-mentioned albumen or composition
It is not limited to protein level, can also be that the modification such as gene level, including phosphorylation, acetylation is horizontal.
In one embodiment, the Keratin 1 further includes protein structure variation, wherein the protein structure includes angle
Albumen 1 and other albumen such as Keratin 10 are formed by dimeric structure, and wherein Keratin 1 includes lack part amino acid sequence
The Keratin 1 segment of column, i.e., the described protein structure include the Keratin 1 segment and other albumen examples of lack part amino acid sequence
As Keratin 10 is formed by dimeric structure.
Another aspect of the present invention provides the method for a kind of diagnosis and prediction ultraviolet induced skin damage, including following
Step:
(1) after skin is irradiated with ultraviolet radiation damage, detect the Keratin 1 in the skin epidermis of subject content,
At least one of structure；
(2) it detects the subject and is not affected by the content of the Keratin 1 in the skin epidermis under ultraviolet radiation damage, knot
At least one of structure；
(3) content, the structure of the Keratin 1 obtained in step (1) and step (2) are compared, calculates corresponding variation
Rate；
(4) according to the change rate, diagnose or predict the ultraviolet induced skin degree of injury of the subject.
The present invention also provides a kind of non-diagnostic therapeutic purposes to detect the method that ultraviolet induced skin damages, including following
Step:
(1) after the skin of experimental subjects is by the light source irradiation comprising doses ultraviolet light, the experiment pair is detected
As at least one of Keratin 1 degradation product content, structure in the skin by the light source irradiation containing ultraviolet light, wherein described dose
Amount=uv power × irradiation time；
(2) Keratin 1 that the experimental subjects is not affected by the skin epidermis of the light source irradiation containing ultraviolet light is equally detected
At least one of the content of degradation product, structure；
(3) content, the structure of the Keratin 1 degradation product obtained in step (1) and step (2) are compared, is calculated corresponding
Change rate；
(4) according to the change rate, monitor or predict the ultraviolet induced skin degree of injury or skin of the subject
Health status.
In a specific embodiment, the time point of test experience object be skin by certain oxidative stress condition at
Reason or under the influence of 0-30 days in test experience object, in preferably 7 days, in more preferable 3 days.
In the present invention, ultraviolet light includes one of UVB, UBC or a variety of.
In one embodiment, the Keratin 1 includes one of gene level, protein level, protein structure
Or it is a variety of.Wherein, Keratin 1 includes but is not limited to the Keratin 1 of overall length or the angle of Keratin 1 lack part amino acid sequence
The mixing of 1 segment of albumen or the segment albumen and overall length Keratin 1 detects above-mentioned albumen and is not limited to protein level, can be with
It is that the modification such as gene level, including phosphorylation, acetylation is horizontal.
In one embodiment, the Keratin 1 further includes protein structure variation, wherein the protein structure includes angle
Albumen 1 and other albumen such as Keratin 10 are formed by dimeric structure, and wherein Keratin 1 includes its lack part amino acid
The Keratin 1 segment of sequence, i.e., the described protein structure include the Keratin 1 segment and other albumen of lack part amino acid sequence
Such as Keratin 10 is formed by dimeric structure.
In the present invention, the Keratin 1 segment of lack part amino acid sequence is also referred to as Keratin 1 degradation product, is selected from
The Keratin 1 segment of any several amino acid, the missing can be the missing of the N-terminal of Keratin 1 between missing 1 to 644, can also
Be Keratin 1 C-terminal missing, can also be the combined missing of arbitrary amino acid in Keratin 1 complete sequence.Such as it lacks
1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、 19、20、21、22、23、24、25、26、27、28、
29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、 51、52、53、
54、55、56、57、58、59、60、61、62、63、64、65、66、 67、68、69、70、71、72、73、74、75、76、77、78、
79、80、81、82、 83、84、85、86、87、88、89、90、91、92、93、94、95、96、97、98、 99、100、101、102、
103、104、105、106、107、108、109、110、111、 112、113、114、115、116、117、118、119、120、121、
122、123、124、 125、126、127、128、129、130、131、132、133、134、135、136、137、 138、139、
140、141、142、143、144、145、146、147、148、149、150、 151、152、153、154、155、156、157、158、
159、160、161、162、163、 164、165、166、167、168、169、170、171、172、173、174、175、176、
177、178、179、180、181、182、183、184、185、186、187、188、189、 190、191、192、193、194、195、
196、197、198、199、200、201、202、 203、204、205、206、207、208、209、210、211、212、213、214、
215、 216、217、218、219、220、221、222、223、224、225、226、227、228、 229、230、231、232、
233、234、235、236、237、238、239、240、241、 242、243、244、245、246、247、248、249、250、251、
252、253、254、 255、256、257、258、259、260、261、262、263、264、265、266、267、 268、269、
270、271、272、273、274、275、276、277、278、279、280、 281、282、283、284、285、286、287、288、
289、290、291、292、293、 294、295、296、297、298、299、300、301、302、303、304、305、306、
307、308、309、310、311、312、313、314、315、316、317、318、319、 320、321、322、323、324、325、
326、327、328、329、330、331、332、 333、334、335、336、337、338、339、340、341、342、343、344、
345、 346、347、348、349、350、351、352、353、354、355、356、357、358、 359、360、361、362、
363、364、365、366、367、368、369、370、371、 372、373、374、375、376、377、378、379、380、381、
382、383、384、 385、386、387、388、389、390、391、392、393、394、395、396、397、 398、399、
400、401、402、403、404、405、406、407、408、409、410、 411、412、413、414、415、416、417、418、
419、420、421、422、423、424、425、426、427、428、429、430、431、432、433、434、435、436、 437、
438、439、440、441、442、443、444、445、446、447、448、449、 450、451、452、453、454、455、456、
457、458、459、460、461、462、 463、464、465、466、467、468、469、470、471、472、473、474、475、
476、477、478、479、480、481、482、483、484、485、486、487、488、 489、490、491、492、493、494、
495、496、497、498、499、500、501、 502、503、504、505、506、507、508、509、510、511、512、513、
514、 515、516、517、518、519、520、521、522、523、524、525、526、527、 528、529、530、531、
532、533、534、535、536、537、538、539、540、 541、542、543、544、545、546、547、548、549、550、
551、552、553、 554、555、556、557、558、559、560、561、562、563、564、565、566、 567、568、
569、570、571、572、573、574、575、576、577、578、579、 580、581、582、583、584、585、586、587、
588、589、590、591、592、 593、594、595、596、597、598、599、600、601、602、603、604、605、
606、607、608、609、610、611、612、613、614、615、616、617、618、 619、620、621、622、623、624、
625、626、627、628、629、630、631、 632、633、634、635、636、637、638、639、640、641、642、643、
One or more of the Keratin 1 segment of 644 amino acid.
In one embodiment, the detection Keratin 1 or Keratin 1 degradation product content, the method for structure include immune
Trace, immunohistochemistry, immunofluorescence, fluorescence spectrum, Raman spectrum, optical detection or physical property detect one or more.
Another aspect of the present invention additionally provides a kind of model, which is used for the inhibition of ultraviolet induced skin damage
Or the screening of exciting drug, which is characterized in that construct the screening model using method of the present invention.
Invention further provides the model in preparation for treating in the drug that ultraviolet induced skin damages
Using.
Detailed description of the invention
Fig. 1 shows UVB and handles in 6 hours, KRT1 content decline figure.
Fig. 2 shows UVB to handle in 7 days, and HE dyes epidermal shape variation diagram.
Fig. 3 shows UVB and handles in 7 days, and HE dyes ear metamorphosis figure.
Fig. 4 shows UVC and handles in 1 hour, KRT1 content decline figure, the constant figure of KRT10 content.
Fig. 5 shows UVC and handles in 3 days, and HE dyes epidermal shape variation diagram.
Fig. 6 shows UVC and handles in 3 days, and HE dyes ear metamorphosis figure.
Specific embodiment
Below will be by specifically describing, the present invention is further illustrated.
Unless otherwise defined, all technical and scientific terms used herein have and the technical field of the invention
Those of ordinary skill be generally understood identical meaning.
As used herein, " Keratin 1 ", " keratin 1 ", " KRT1 " are interchangeable, and being includes being able to use Keratin 1
The keratin of antibody recognition detection, can be single substance, be also possible to mixture；In the present invention, Keratin 1 includes it
The Keratin 1 segment of lack part amino acid sequence, the Keratin 1 segment of the lack part amino acid sequence are Keratin 1
The end N or C-terminal lack any Keratin 1 segment or combinations thereof in 1 to 644 amino acid.
As used herein, " the Keratin 1 segment of lack part amino acid sequence ", " Keratin 1 degradation product ", " degradation
Object " is interchangeable, refer to the N-terminal of Keratin 1 or C-terminal lack in 1 to 644 amino acid any Keratin 1 segment or its
Combination.
The variation of subcutaneous fluorescence after embodiment 1UVB irradiation
Hypotype is numerous in keratin family, and Various Functions.In epithelial cell, keratin participates in a variety of important function
Can, the formation including intermediate filament, inflammatory reaction, cellular signal transduction etc..And the albumen with keratin interaction, quantity is just more
Add it is huge, it is close hundreds of, and this number is being continuously increased also as discovery of scientific research, thus keratin family and and this
The marker with detection and accurate prediction skin injury is found in a little albumen in interaction protein, it is significant.The present invention
The Keratin 1 of middle discovery have clarify a diagnosis and predict it is ultraviolet caused by skin injury ability, have good medical value.
According to the present invention, using male C57 mouse, the mice weights of UVB irradiation are between 18-25g range.Radiation is completed
Afterwards, mouse is raised in animal house, and condition is 22-24 DEG C, 12 hours light/dark circulations, and can ad lib water intaking.
Thereafter 2 hours, 6 hours sacrifice mouse took damage skin to carry out immune protein Blot experiment, measure Keratin 1
Content.Mouse is sacrificed after one day or five days, takes injured cutaneous tissue, carries out H&E (Hematoxylin & Eosin dyeing) detection.
The storage of skin histology: it after skin takes out, takes out appropriate tissue and is soaked in 4% paraformaldehyde, for making paraffin
Slice, remaining tissue is wrapped with aluminium-foil paper, using liquid nitrogen frozen, is transferred to -80 DEG C of refrigerator long-term preservations later.
Skin histology paraffin section: skin histology is impregnated into 4% paraformaldehyde solution for 24 hours, then according to paraffin section
Production method successively soaks tap water, distilled water, graded ethanol, dimethylbenzene, paraffin, is fabricated to paraffin section.
The H&E of skin paraffin section is dyed: by paraffin section leaching dimethylbenzene dewaxing, being then successively dipped in graded ethanol, is steamed
Distilled water, haematoxylin dyeing 10 minutes, tap water flowing water rinsed 30 minutes, and distilled water immersion 30 seconds, 95% ethyl alcohol 10s, Yihong was multiple
Dye 30 seconds, 70% ethanol wash 2 times successively soak graded ethanol, dimethylbenzene, resinene mounting.
It takes pictures, quantify to coloration result: taking pictures to above two dyeing.And it is directed to epidermal cornified thickness, epidermis
The indexs such as thickness are quantified.
Statistical analysis: all data provide in the way of mean+SD, and data use one-way analysis of variance
It is assessed, P value is considered statistically significant less than 0.05.
Immune protein Blot experiment (western blot)
1. prepared by protein sample
After chloraldurate excess anesthetized animal, ear tissue is taken, is put into the EP pipe of weighing, lysate is added, is placed in
On ice, it grinds, lysate is added, -80 degree refrigerators are stored in after the packing of centrifuging and taking supernatant.
2. determination of protein concentration
According to the specification of BCA kit, normal concentration albumen is prepared.
3.SDS polyacrylamide gel electrophoresis
Prepared gel is fixed in electrophoretic apparatus, protein sample is added respectively.Electrophoresis, transferring film, milk room temperature
Primary antibody is added after closing, TBST washing to stay overnight.The secondary antibody of HRP label is added in TBST after washing.Finally with developing solution to cellulose nitrate
Film develops the color, and exposure is taken pictures in imaging systems.
Experimental result is as shown below:
Treated the 2nd hour by UVB, after 6 hours, it is found that the content of Keratin 1 is remarkably decreased.And positive is presented with the time
Pass trend (Fig. 1).Figure 1A is that protein immunoblot represents figure, and Figure 1B is quantization figure.Ear does not observe that skin damages at this time
Wound.
Then, at the 1st, 3,7 day of UVB processing, by finding skin epidermis in UVB to epidermal tissue's slice HE dyeing
When treated the 1st day, obviously do not thicken.When treated the 3rd day by UVB, presentation is significantly thickened.In UVB, treated
It significantly thickens within 7th day, and degree is higher than 3 days.Epidermis, which thickens, to be represented UVB and causes skin injury (Fig. 2A and 2B).
More obviously, UVB is handled 1,3,7 day, and slice HE dyeing, finding the ear of mouse, treated the 1st day in UVB
When, obviously do not thicken.When treated the 3rd day, presentation significantly thickens UVB.Treated the 7th day significantly thickens by UVB, and journey
Degree is higher than 3 days.Wherein, ear, which thickens, represents UVB and causes skin injury (Fig. 3 A and 3B).
It can be concluded that, after ultraviolet light (UVB) irradiation, Keratin 1 content changes skin by testing above,
The reason is that because foring the degradation product of Keratin 1.And the variation of Keratin 1 (including its degradation product) and skin injury are in positive
It closes.Therefore, the variation prediction skin injury degree of Keratin 1 (including its degradation product) content can be used.
Inventor also found that the UVB processing of various dose has obtained above-mentioned similar as a result, i.e. skin shines by UVB
After penetrating, the content of the Keratin 1 in skin epidermis tissue declines, and produces Keratin 1 degradation product, the molecular weight of the degradation product is small
In overall length keratin molecule amount.In addition, inventor is counted through a large number of experiments it has been found that detecting Keratin 1 after UVB processing
Content declines 5% or more (such as 5%, 10%, 15%, 20%, 30%, 50% or more), or detects the degradation of Keratin 1
When object, after detecting the after Keratin 1 the 2nd day time point (such as detection Keratin 1 after the 2nd day, the 3rd day, the 4th day,
5th day, the 6th day, the 7th day or one week or more, such as 2 weeks or more, 1 month with first-class) it can be observed that dermal tissue insult.
This illustrates marker of the Keratin 1 as prediction, and sensitivity is very high, can pass through when damage occurs not yet
The formation of changes of contents and Keratin 1 degradation product occurred to predict subsequent insult.
However, (keratin 2,5,10 etc. and interaction protein etc. are close for other keratin hypotypes in addition to Keratin 1
Hundreds of albumen) and correlation marker without discovery not can be used in predict skin injury.Also the special of Keratin 1 is absolutely proved
Property is very high.
The variation of subcutaneous fluorescence after 2 UVC of embodiment irradiation
According to the present invention, using male C57 mouse, the mice weights of UVC irradiation are between 18-25g range.Radiation is completed
Afterwards, mouse is raised in animal house, and condition is 22-24 DEG C, 12 hours light/dark circulations, and can ad lib water intaking.
Thereafter mouse is sacrificed in 1 hour, takes damage skin to carry out immune protein Blot experiment, measures the content of Keratin 1.
Mouse is sacrificed after one day or three days, takes injured cutaneous tissue, carries out H&E (Hematoxylin & Eosin dyeing) detection.
The storage of skin histology: it after skin takes out, takes out appropriate tissue and is soaked in 4% paraformaldehyde, for making paraffin
Slice, remaining tissue is wrapped with aluminium-foil paper, using liquid nitrogen frozen, is transferred to -80 DEG C of refrigerator long-term preservations later.
Skin histology paraffin section: skin histology is impregnated into 4% paraformaldehyde solution for 24 hours, then according to paraffin section
Production method successively soaks tap water, distilled water, graded ethanol, dimethylbenzene, paraffin, is fabricated to paraffin section.
The H&E of skin paraffin section is dyed: by paraffin section leaching dimethylbenzene dewaxing, being then successively dipped in graded ethanol, is steamed
Distilled water, haematoxylin dyeing 10 minutes, tap water flowing water rinsed 30 minutes, and distilled water immersion 30 seconds, 95% ethyl alcohol 10s, Yihong was multiple
Dye 30 seconds, 70% ethanol wash 2 times successively soak graded ethanol, dimethylbenzene, resinene mounting.
It takes pictures, quantify to coloration result: taking pictures to above two dyeing.And it is directed to epidermal cornified thickness, epidermis
The indexs such as thickness are quantified.
Statistical analysis: all data provide in the way of mean+SD, and data use one-way analysis of variance
It is assessed, P value is considered statistically significant less than 0.05.
Immune protein Blot experiment (western blot)
1. prepared by protein sample
After chloraldurate excess anesthetized animal, ear tissue is taken, is put into the EP pipe of weighing, lysate is added, is placed in
On ice, it grinds, lysate is added, -80 degree refrigerators are stored in after the packing of centrifuging and taking supernatant.
2. determination of protein concentration
According to the specification of BCA kit, normal concentration albumen is prepared.
3.SDS polyacrylamide gel electrophoresis
Prepared gel is fixed in electrophoretic apparatus, protein sample is added respectively.Electrophoresis, transferring film, milk room temperature
Primary antibody is added after closing, TBST washing to stay overnight.The secondary antibody of HRP label is added in TBST after washing.Finally with developing solution to cellulose nitrate
Film develops the color, and exposure is taken pictures in imaging systems.
Experimental result is as follows:
UVC was handled in 1 hour, used UVC 0.33J/cm2Processing group, 0.66J/cm2Processing group discovery Keratin 1 contains
Amount is remarkably decreased, and is positively correlated (Fig. 4 A) with the dosage of UVC.However, it is same as the important composition in keratin family it
The content of one Keratin 10 is but without variation (Fig. 4 B)
Fig. 5 show UVC handle the 1st, 3 day, slice HE dyeing, as a result, it has been found that skin epidermis on day 1 when, horn cell
Do not significantly reduce.But when on day 3, horn cell is substantially reduced, and the dosage of degree and UVC are positively correlated.Horn cell
Reduction represents skin injury caused by UVC.
Fig. 6 has used the 1st, 3 day of UVC processing, and slice HE dyeing does not obviously increase when finding skin ear on day 1
It is thick.At the 3rd day, presentation is significantly thickened.Ear, which thickens, to be represented UVC and causes skin injury.
It can be concluded that, skin is after ultraviolet light (UVC) irradiation, and Keratin 1 content changes, shape by testing above
At the degradation product of Keratin 1.And the variation is positively correlated with skin injury.Therefore, the variation of Keratin 1 and its degradation product content
It can predict skin injury degree.
Those skilled in the art is it should be understood that although for illustrative purposes, this document describes tools of the invention
Body embodiment, but it can be carry out various modifications without departing from the spirit and scope of the present invention.Therefore, of the invention specific
Embodiments and examples should not be considered as limiting the scope of the invention.The present invention is limited only by the appended claims.This Shen
Please in quote all documents be fully incorporated herein by reference.
Claims (12)
1. molecular marked compound is in preparation for diagnosing and predicting the reagent or reagent of the damage of ultraviolet induced skin cell or tissue
Application in box, which is characterized in that the molecular marked compound includes Keratin 1.
2. application as described in claim 1, which is characterized in that the detection of the molecular marked compound includes gene level, albumen
One of matter level and protein structure variation are a variety of.
3. application as claimed in claim 1 or 2, which is characterized in that the molecular marked compound further includes lack part amino acid
The Keratin 1 segment of sequence.
4. a kind of method of diagnosis and prediction ultraviolet induced skin damage, comprising the following steps:
(1) after skin is irradiated with ultraviolet radiation, the content of the Keratin 1 in the skin epidermis of subject is detected, in structure
It is at least one；
(2) it detects the subject and is not affected by the content of the Keratin 1 in the skin epidermis under ultraviolet radiation damage, in structure
At least one；
(3) content, the structure of the Keratin 1 obtained in step (1) and step (2) are compared, calculates corresponding change rate；
(4) according to the change rate, diagnose or predict the ultraviolet induced skin degree of injury of the subject.
5. method as described in claim 4 detects skin table in the method for the prediction ultraviolet induced skin damage
When the time point of the Keratin 1 in skin, skin epidermis, which can't be observed, has damage.
6. a kind of method of non-diagnostic therapeutic purposes detection ultraviolet induced skin damage, comprising the following steps:
(1) after the skin of experimental subjects is by the light source irradiation comprising doses ultraviolet light, the experimental subjects warp is detected
At least one of Keratin 1 content, structure in the skin of the light source irradiation containing ultraviolet light are crossed, wherein the dosage=ultraviolet light
Power x irradiation time；
(2) containing for the Keratin 1 that the experimental subjects is not affected by the skin epidermis of the light source irradiation containing ultraviolet light is equally detected
At least one of amount, structure；
(3) content, the structure of the Keratin 1 obtained in step (1) and step (2) are compared, calculates corresponding change rate；
(4) according to the change rate, monitor or predict the ultraviolet induced skin degree of injury or skin health of the subject
State.
7. the method as described in any one of claim 4 to 6, which is characterized in that the ultraviolet light includes one in UVB, UVC
Kind or more.
8. the method as described in any one of claim 4 to 6, which is characterized in that the detection of the Keratin 1 includes gene water
One of flat, protein level, protein structure switch are a variety of.
9. the method as described in any one of claim 4 to 6, which is characterized in that the Keratin 1 further includes lack part ammonia
The Keratin 1 segment of base acid sequence.
10. such as method described in any one of claims 1 to 6, which is characterized in that the detection Keratin 1 content, structure
Method includes immunoblotting, immunohistochemistry, immunofluorescence, fluorescence spectrum, Raman spectrum, optical detection or physical property detection
It is one or more.
11. a kind of model, which exists for the inhibition of ultraviolet induced skin damage or the screening of exciting drug, feature
In constructing the screening model using method described in any one of claim 4 to 10.
12. model as claimed in claim 11 is in preparation for treating the application in the drug that ultraviolet induced skin damages.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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