CN104721842B - Application of the honey in the long time-histories near-infrared targeted imaging reagent of inflammation part dynamic - Google Patents
Application of the honey in the long time-histories near-infrared targeted imaging reagent of inflammation part dynamic Download PDFInfo
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Abstract
The invention discloses application of the honey in the long time-histories near-infrared targeted imaging reagent of inflammation part dynamic, the reagent is made of the excellent honey of biocompatibility, propolis and royal jelly, any one or arbitrary two kinds of mixtures formed with arbitrary proportion therein, and fast imaging label is precisely targeted to inflammation correlation lesions position by the effect of biology in situ fixed point；It can realize the highly sensitive quick tracer and monitoring of the real-time long time-histories of dynamic of non-intrusion type, and inanimate object toxic side effect, detection method are simple and easy to do.Such reagent may be implemented, to the real-time of inflammation part, dynamic, long time-histories, near-infrared targeted imaging and related multi-modality imaging, have wide medical application foreground.
Description
Technical field
The present invention relates to application of the honey in the long time-histories near-infrared targeted imaging reagent of inflammation part dynamic, these reagents
Be made of the excellent honey of biocompatibility, propolis and royal jelly, it is therein any one or it is arbitrary two kinds with arbitrary proportion group
At mixture, the near infrared imaging of Fast Labeling precisely targets inflammation correlation lesions position by the effect of biology in situ fixed point
And its relevant multi-modality imaging, the highly sensitive quick tracer and monitoring of the real-time long time-histories of dynamic of non-intrusion type may be implemented,
And inanimate object toxic side effect, detection method are simple and easy to do.
Background technology
Inflammation refers to the defense reaction that there is the living tissue of vascular system damage factor to be occurred.It is exactly usually people
Described " inflammation ", it is a kind of extremely common and important pathologic process, is a kind of defense reaction of the body for stimulation,
Show as red, swollen, hot, pain.Vascular reaction is the key link of inflammatory process.Under normal circumstances, inflammation is beneficial, is human body
Automatic defense reaction.But in some cases, inflammation is also harmful, because it causes the attack to human body autologous tissue.
Common inflammation related disease type is various, includes mainly：Cardiovascular and cerebrovascular disease, eye disease, liver disease, pulmonary disease,
Stomach trouble, duodenal ulcer, ephritis, diabetes, arthritis and rheumatism, trauma infection contamination and various other communicable diseases
And therefore Deng there are common laws of inflammatory disorders to have different pathogeny to cause since disease is happened at Different Organs for they,
Show respectively special rule.
Any the reason of capable of causing the factor of tissue damage that can all become inflammation, i.e. pro-inflammatory cytokine.It can be summarized as following
Several classes：(1) biological factors bacterium, virus, Richettsia, mycoplasma, fungi, conveyor screw and parasite etc. are that inflammation is most normal
The reason of seeing.(2) physics sex factor high temperature, low temperature, radioactive substance and ultraviolet light etc. and mechanical damage.(3) chemically because
Sub- xenobiotics such as strong acid, highly basic and turpentine oil, mustard gas etc..The decomposition of endogenous cytotoxic substance such as slough is produced
Object and internal metabolite such as urea is piled up under certain pathological conditions etc..(4) foreign matter enters human body by all means
Foreign matter, such as various metals, wood chips, dust granules and sutures can cause difference since its antigenicity is different
The inflammatory reaction of degree.(5) reasons such as slough ischemic or anoxic can cause tissue necrosis, tissue necrosis to be potentially to cause
The scorching factor.(6) allergy can cause inappropriate or excessive immune response, cause when organism immune response abnormal state
Tissue and cellular damage and lead to inflammation.Tissue damage caused by immune response is most commonly in various types of hypersensitivity.
Above-mentioned common various inflammation related diseases bring great pain to individual invariably, are brought to family very heavy
Burden, brings prodigious influence, and prodigious pressure is all brought to entire society to daily life and work.
With the progress of science and technology, there are many Imaging Methods and biomarker to be applied to clinical diagnosis, existing common
Include mainly MRI (Magnetic resonance imaging), SPE-CT (single photon emission tomographies in diagnosing the Imaging Method of inflammation related disease
Imaging), PET (positron emission tomography), x-ray, electrocardiogram, routine CT (CR scanning) etc. are a variety of, so
And the method for these above-mentioned common diagnosis inflammation diseases has certain limitation, such as：MRI (Magnetic resonance imaging) and
SPE-CT (single photon emission tomographic imaging) lacks specificity, and PET (positron emission tomography) is expensive, limits
Its application.Therefore, a kind of diagnosis and treatment examination that real-time, dynamic, long time-histories, near infrared imaging can be carried out to inflammation related disease is found
Agent is particularly important.However, up to the present, real-time, dynamic, long time-histories, near-infrared can be carried out to inflammation related disease by having not yet to see
The report of imaging agents.
The main ingredient of honey is carbohydrate, and carbohydrate accounts for the 65%~80% of honey gross mass, is secondly protein, dimension life
Element, acids, enzyme, inorganic salts etc..Carbohydrate mainly has glucose, fructose, sucrose, a small amount of maltose, vitamin mainly have B2, B12,
B6, carrotene etc., acids have lactic acid, oxalic acid, malic acid, citric acid etc., enzyme mainly to have amylase, glucose oxidase, mistake
Oxide enzyme etc., inorganic salts mainly have more than 20 kinds of calcium, phosphorus, chlorine, magnesium, potassium, iron, zinc, selenium etc., and have a small amount of fat, auxin etc..
Honey contained substance type is various, determines that honey has unique physical and chemical performance and biological function.
The main active material of two classes is flavonoids and phenolic acid compound in honey.It is many studies have shown that flavonoids and
The healthcare function of phenolic acid compound is mainly manifested in：Interior free yl, vasodilator, anticancer, antiviral, antibacterial is removed to disappear
Inflammation, antiallergy generate cancer cell blood vessel blocking element, stimulation immuning system generating antibody, inhibit phosphatidase, lipoxidase, ring
The activity of the enzymes such as oxygenase, xanthine oxidase.Therefore, the research of honey has been to be concerned by more and more people in recent years.
Propolis and royal jelly chemical composition be mainly organic acid, flavonoids, alkane, alkene, ester, alcohol, aldehyde, terpenoid and
30 various trace elements and minerals etc..Containing a large amount of ingredients with health role in propolis and royal jelly, researches show that bees
Glue and royal jelly all have that antiviral, anti-oxidant, antibacterial, antitumor (such as propolis is to ovarian cancer cell, colon cancer cell, marrow
The growths such as cancer cell, leukaemia cell, breast cancer cell, lymphoma cell have inhibiting effect), anti-corrosive fresh-keeping and anti-inflammatory analgesic
Etc. a variety of effects, and the oxidation resistance of the two is more stronger than honey.
Under normal circumstances, the generation of people's interior free yl and remove in the dynamic equilibrium, when body by certain diseases or
After exogenous material (such as various radioactive ray) invasion, Radical Metabolism will be abnormal, and can lead to cell and histoorgan
Damage induces various different inflammation related diseases, accelerates body aging.It is many to be rich in antioxidant studies have shown that absorbing
Diet can effectively prevent and the relevant a variety of diseases of free radical.Antioxidant in food has safe, without side-effects
The advantages that, therefore the food honey rich in antioxidant, propolis, royal jelly are favored by people always deeply.
Reagent honey of the present invention, propolis, royal jelly good biocompatibility, have no toxic side effect, can be by inflammation
The specific enrichment at relevant diseases position, realize to inflammation related disease carry out in real time, dynamic, long time-histories, near infrared imaging and
Multi-modality imaging has wide medical application foreground.
Invention content
Technical problem：For the defect of current existing detection technique, it is long in inflammation part dynamic that the invention discloses honey
Application in time-histories near-infrared targeted imaging reagent, these reagents are by the excellent honey of biocompatibility, propolis and royal jelly group
At any one or arbitrary two kinds of mixtures formed with arbitrary proportion therein are passed through the effect of biology in situ fixed point and realized pair
Related lesions position precisely targets the near infrared imaging detection of Fast Labeling, and the multi-modality imaging of related lesion and non-may be implemented
Intrusive real-time dynamic highly sensitive quick tracer and monitoring, and inanimate object toxic side effect, detection method are simple and easy to do.
Technical solution：In order to solve the above-mentioned technical problem, a kind of honey of the invention is close in the long time-histories of inflammation part dynamic
In application in infrared targeted imaging reagent, the reagent is made of the excellent honey of biocompatibility, propolis and royal jelly,
In any one or arbitrary two kinds of mixtures formed with arbitrary proportion, acted on to inflammation related diseases by biology in situ fixed point
Stove position precisely targets fast imaging label.
The inflammation refers to：Cardiovascular and cerebrovascular disease, eye disease, liver disease, pulmonary disease, ephritis, stomach trouble, 12 refer to
Enterelcosis, diabetes, arthritis and rheumatism, trauma infection contamination and various other communicable diseases.
The imaging refer in real time, dynamic, long time-histories, near infrared imaging.
The application includes the following steps：By the reagent for inflammation disease image areas and treatment when, by honey, propolis or
Royal jelly is by tail vein injection or local injection and microinjection to the animal model of wound-induced, honey, propolis or bee
Royal jelly reagent can be quickly enriched in lesions position, be imaged using small animal living body phosphorimager and macroscopical zoom fluorescence microscope
Instrument is to the real-time dynamic imaging of animal pattern.
This method comprises the concrete steps that：
1) transgenic drosophila model for building wound-induced inflammation, is divided into experimental model group and comparison model group, while setting up normal
Control group and blank control group；
2) model mouse for building wound-induced inflammation, is divided into experimental model group and comparison model group, at the same set up it is normal right
According to group and blank control group；
3) by honey, propolis and the royal jelly of a concentration of 1~50g/L sterile 0.01~0.5mL, it is injected into experimental model
In group and comparison model group, Normal group and blank control group are not processed.By 1 hour to one week or more non-intrusion type
Real-time dynamic highly sensitive quick tracer and monitoring, observation body-internal-circulation realizes that reagent exists on the animal model with inflammation
The specific enrichment of diseased region is imaged to the accurate targeting Fast Labeling of related lesions position；
4) using macroscopical zoom fluorescence microscope imaging, living body fluorescent imaging, ultrasonic imaging, CR scanning
The means of CT and magnetic Resonance Imaging MRI carry out living imaging to inflammation correlation lesions position and carry out qualitative and quantitative point to it
Analysis；
5) anatomical model group, control group and naive animals take whole blood and serum, test blood routine and aspartic acid turns ammonia
The index of enzyme, glutamic-pyruvic transaminase, lactase dehydrogenase, creatine kinase and urea nitrogen；Organ liver,spleen,kidney and periwound tissue are taken,
Prepare pathological section, influence of the analytical reagent for experimental animal.
The injecting method is tail vein injection, local injection or microinjection.
Advantageous effect：The present invention has the following advantages and effect compared with art methods：
This research use reagent be made of the excellent honey of biocompatibility, propolis and royal jelly reagent, by with target
To the accurate of bioactive molecule fixed point effect lesions position related to the specific microenvironment realization such as internal hypoxic-ischemic is targeted
Targeting label is detected with fast imaging, can carry out the real-time dynamic highly sensitive quick tracer and monitoring of live body non-intrusion type, and
Inanimate object toxic side effect, live body targeted imaging determination method are simple and easy to do.The result shows that：Pass through CT (computerized tomographies
Scanning), ultrasound, the image checkings such as fluorescence and MRI (Magnetic resonance imaging), which can precisely guide, quickly identification targeting
Lesions position is simultaneously enriched in the region, tests, dynamic real-time to the site of pathological change of model group animal, long time-histories, near infrared imaging
And its multi-modality imaging of related lesion.These results suggest that such reagent may be implemented to cardiovascular and cerebrovascular disease, eye disease,
Liver disease, pulmonary disease, stomach trouble, duodenal ulcer, ephritis, diabetes, arthritis and rheumatism, trauma infection contamination and
Various other communicable diseases etc. in real time, dynamic, long time-histories, near infrared imaging, and can realize multi-modal CT (computer x-ray break
Layer scanning), ultrasound, fluorescence and MRI (Magnetic resonance imaging) imaging.Not damaged, in situ, real-time, dynamic can be achieved in the invention
The near infrared imaging of inflammation disease is targeted, polymorphic diagnosis synchronous with multi-modal and accurate targeting positioning and treatment, tool are carried out
There is wide medical application foreground.
Specific implementation mode
The following description is substantially only exemplary and is not intended to the limitation disclosure, application or purposes.
Embodiment 1
Application of the honey in the long time-histories near-infrared targeted imaging reagent of inflammation part dynamic, step are：
1) in the lower abdomen cage structure wound of drosophila, inflammatory model is induced, experimental model group is set as；Set up normal control simultaneously
Group and blank group.
2) it by honey, propolis or the royal jelly of a concentration of 30g/L sterile 0.05ml, is injected and is entered in fact by microinjection instrument
It tests in model group and Normal group body；Blank group is not processed.
3) during 1~6 hour, pass through the highly sensitive rapid fluorescence tracer of real-time dynamic and detection of non-intrusion type, observation
Imaging agents transport in drosophila body and are enriched in inflammation foci position；Concrete operations are：
Using imagings such as macroscopical zoom fluorescence microscopes, 1 hour, 2 hours, the different time points such as 6 hours are chosen respectively, it will
Drosophila CO2Anesthesia, is placed on microscope operating platform, and 480nm equiwavelength is selected to excite acquisition fluorescent image.
4) the step 2) reagent is one kind in honey, propolis or royal jelly or arbitrary two kinds of mixture.
The results show that imaging agents, in the focal area of the drosophila of experimental model group, fluorescence intensity is presented at any time first to be increased
The variation weakened after adding, and imaging time can be up to 72 hours or more, and be imaged near infrared region.Illustrate related reagent
Such as honey, propolis or royal jelly can be acted on by the biological targeting of itself and be enriched in inflammatory disorders region precisely to guide,
Carry out the biology in situ reaction of specificity, last and gradually metabolism；Control group and blank group fluorescence are weaker and without significant change.
Embodiment 2
1) cause wound in C57 mouse neck or head, or the inflammatory models such as induction cerebral apoplexy, be divided into experimental model group and
Comparison model group；Set up Normal group and blank group control group simultaneously.
2) by the honey, propolis or royal jelly of a concentration of 30g/L sterile 0.3ml one kind or arbitrary two kinds of mixing
Object reagent solution, injection enter in Normal group and experimental model group Mice Body；Comparison model group and blank group are not processed.
3) during 1~72 hour, pass through the highly sensitive rapid fluorescence tracer of real-time dynamic and monitoring of non-intrusion type, observation
Targeting agent is in mouse body-internal-circulation and is enriched in inflammation foci position；The specific steps are：
It is imaged using living body fluorescent imager, is chosen 1 hour, 4 hours, 8 hours, 12 hours, 24 hours, 48 hours respectively
Etc. different time points, mouse is then subjected to gas anesthesia with 5% isoflurane, it is flat to place it in small animal living body imager operation
On platform, 520nm and 480nm equiwavelengths is selected to excite the image in acquisition inflammatory disorders region.
4) anatomical model group, control group and naive mice take whole blood and serum, test blood routine and aspartic acid turns ammonia
The index of enzyme, glutamic-pyruvic transaminase, lactase dehydrogenase, creatine kinase and urea nitrogen；Organ liver,spleen,kidney and periwound tissue are taken,
Pathological section is prepared, influence of the multi-modal treatment of targeting agent for C57 mouse is analyzed.
5) injecting method described in step 2) is tail vein or local injection；One in the honey, propolis or royal jelly
Kind or arbitrary two kinds of mixture.
The results show that fluorescence intensity of the imaging agents in the focal area of inflammatory model mouse presents first to increase at any time and subtract afterwards
Weak variation illustrates that honey, propolis or royal jelly reagent can be enriched in inflammatory disorders region by the accurate guiding of itself, into
The fabricated in situ of row specificity, then gradually metabolism again；Control group and blank group fluorescence are weaker and without significant change.Blood and disease
Reason analysis, the nape wound therapeutic effect of experimental model group mouse improve significantly compared with comparison model group mouse, simultaneously
It is not significantly different between Normal group and the result of blank group.
It is enriched in diagnosis and treatment reagent honey, propolis or the royal jelly of lesions position and contains a large amount of carbohydrate, flavonoids and phenol
Acid compounds and trace element etc., they can with fast accurate be enriched in inflammation foci position, realize in real time, dynamic,
Long time-histories, near infrared imaging, while multi-modal CT (CR scanning), ultrasound, fluorescence and MRI (nuclear-magnetisms can be carried out
Resonance image-forming) etc. multiple dimensioned imaging.
The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention.The technology of the industry
Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the above embodiments and description only describe this
The principle of invention, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these changes
Change and improvement all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and its
Equivalent thereof.
Claims (1)
1. a kind of application of honey in preparing the long time-histories near-infrared targeted imaging reagent of inflammation part dynamic, which is characterized in that
The near-infrared targeted imaging reagent is made of the excellent honey of biocompatibility, propolis and royal jelly, fixed by biology in situ
Point effect precisely targets fast imaging label to inflammation correlation lesions position, which includes the following steps：
1) transgenic drosophila model for building wound-induced inflammation, is divided into experimental model group and comparison model group, while setting up normal control
Group and blank control group；
2) model mice for building wound-induced inflammation, is divided into experimental model group and comparison model group, while setting up normal control
Group and blank control group；
3) by honey, propolis and the royal jelly of a concentration of 1~50g/L sterile 0.01~0.5mL, be injected into experimental model group and
In comparison model group, Normal group and blank control group are not processed, by the reality of 1 hour to one week or more non-intrusion type
When dynamic highly sensitive quick tracer and monitoring, observation body-internal-circulation realize reagent in lesion on the animal model with inflammation
The specific enrichment at position is imaged to the accurate targeting Fast Labeling of related lesions position；
4) using macroscopical zoom fluorescence microscope imaging, living body fluorescent imaging means to inflammation correlation lesions position carry out live body at
Picture simultaneously carries out qualitative and quantitative analysis to it；
5) anatomical model group, control group and naive mice, take whole blood and serum, test blood routine and aspartate transaminase,
The index of glutamic-pyruvic transaminase, lactase dehydrogenase, creatine kinase and urea nitrogen；Organ liver,spleen,kidney and periwound tissue are taken, is made
Standby pathological section, influence of the analytical reagent for experiment mice.
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Non-Patent Citations (2)
| Title |
|---|
| Functional Properties of Honey, Propolis, and Royal Jelly;M. VIUDA-MARTOS et al.,;《JOURNAL OF FOOD SCIENCE》;20081231;第73卷;第117-124页 * |
| 基于三维荧光光谱技术对掺假蜂蜜无损鉴别研究;赵杰文等;《光谱学与光谱分析》;20130630;第33卷(第6期);第1626-1630页 * |
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