CN107982250A - Application of the dihydroartemisinine in the acute injury of kidney medicine for the treatment of pyemia induction - Google Patents
Application of the dihydroartemisinine in the acute injury of kidney medicine for the treatment of pyemia induction Download PDFInfo
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Abstract
The present invention provides application of the dihydroartemisinine in the acute injury of kidney medicine for the treatment of pyemia induction.Tests prove that, it is excessive that dihydroartemisinine can substantially suppress glomerular endothelial cells caused by TNF (Tumor Necrosis Factor) alpha (HRGECs) permeability, experiment proves, TNF (Tumor Necrosis Factor) alpha can reduce expression of the Tight junction protein occludin in glomerular endothelial cells, and dihydroartemisinine then has the function that to raise Occludin protein expressions.Therefore, our result indicate that dihydroartemisinine reduces glomerulus endothelial permeability, so as to show ability of the dihydroartemisinine to the acute injury of kidney with treatment pyemia induction by raising the expression of Occludin albumen.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to acute injury of kidney of the dihydroartemisinine in treatment pyemia induction
Application in medicine.
Background technology
Pyemia (Sepsis) refers to the systemic inflammatory response syndrome as caused by infection, is (such as bacterium, true by microorganism
Bacterium, virus, parasite etc.) intrusion human body and the fierce systemic inflammatory response that induces, and to organizing to give birth to damaging pathology
One group of clinical manifestation of reason process, usually secondary to serious disease, such as serious burn, multiple injury, surgical site infections.Serious purulence
Toxication can cause septic shock and multiple organ dysfunction, be in current intensive care unit it is non-cardiac die of illness die it is main
Reason, about 28.3% to 41% sepsis patient is dead because of multiple organ failure, to human health and economic development structure
Threaten and challenge into great.
Acute injury of kidney (acute kidney injury, AKI) is in ICU, most commonly seen and serious in sepsis patient
Complication.Moreover, pyemia and the most important cause of disease that septic shock is critical patients AKI, some researches show that severe
In Intensive Care Unit, acute injury of kidney patient caused by pyemia accounts for the 50% of all patients, and acute injury of kidney is in ICU wards
An important factor for dead, even in developed country, the acute injury of kidney of pyemia induction accounts for all acute injury of kidney patients'
26% to 50%, and although preventative strategies and supporting treatment have obtained today of huge advance, the acute kidney of pyemia induction
The morbidity and mortality of damage are still high.In addition, even if the patient with AKI tides over a critical period, still there is chronicity
Trend, some high risk factors can aggravate the generation of chronic kidney disease (chronic kidney disease, CKD), and accelerate
It is changed into end-stage renal disease (end-stage renal disease, ESRD).
Qinghaosu (Artemisinin) is that separation identifies from sagebruss sweet wormwood (Artemisia carvifolia)
One kind there is the new Sesquiterpene lactones compound of peroxy, its molecular formula is C12H22O5, it is that one kind that China initiates is efficiently low
The new antimalarial of poison, dihydroartemisinine (Dihydroartemisinin, DHA) are first that hydroxyl is introduced from qinghaosu
Derivative, its antimalarial curative effect are significantly improved compared with qinghaosu, in recent years, and are found that it has and are suppressed growth of tumour cell and treat red
Yabbi sore etc. acts on, but so far not yet studies have reported that it has the function that the acute injury of kidney for treating pyemia induction.
The content of the invention
In view of the above shortcomings of the prior art, inventor has been surprisingly found that double hydrogen sweet wormwoods through long-term technology and practical exploration
It is excessive that element can substantially suppress glomerular endothelial cells caused by TNF (Tumor Necrosis Factor) alpha (HRGECs) permeability, experiment card
Bright, TNF (Tumor Necrosis Factor) alpha can reduce expression of the Tight junction protein occludin in glomerular endothelial cells, and double
Hydrogen arteannuin then has the function that to raise Occludin protein expressions.Therefore, our result indicate that dihydroartemisinine pass through it is upper
The expression of Occludin albumen is adjusted, reduces glomerulus endothelial permeability, so as to show dihydroartemisinine to treatment septicopyemia
The ability of the acute injury of kidney of disease induction.
Specifically, the present invention relates to following technical scheme：
The first aspect of the invention, there is provided dihydroartemisinine is preparing the acute injury of kidney medicine for the treatment of pyemia induction
Application in thing；Dihydroartemisinine can be obviously improved the glomerulus oedema occurred in the acute injury of kidney of pyemia induction, go out
Blood and inflammatory symptoms；
Dihydroartemisinine is penetrating in glomerular endothelial cells (HRGECs) caused by preparation suppression TNF (Tumor Necrosis Factor) alpha
Application in the excessive medicine of property；
Dihydroartemisinine raises Occludin protein expressions in the case where preparing inflammatory conditions and is led to reducing glomerular endothelial cells
Application in the excessive medicine of permeability；
Wherein, the inflammatory conditions promotive factor includes TNF (Tumor Necrosis Factor) alpha；
The drug medication valid density for 25 μM and more than, the valid density for reach lesion internal medicine it is dense
Degree；
Preferably, the medicine is also comprising one or more acceptable auxiliary materials pharmaceutically or in bromatology.Auxiliary material used
Can be solid-state or liquid.The preparation of solid-state form includes pulvis, tablet, discrete particles, capsule, pill and suppository.Pulvis and piece
Agent can include about the active ingredient of 0.1% to about 99.9%.Appropriate solid adjuvant material can be magnesium carbonate, magnesium stearate, talcum
Powder, sugar or lactose.Tablet, pulvis, pill and capsule are suitable for solid dosage for oral use.The preparation of liquid form includes molten
Liquid, suspension and lotion, embodiment is parenteral injection aqueous solution or water-propylene glycol solution, or adds sweetener and make
The oral administration solution of shadow agent.In addition, it may also be fabricated which the small liquid drugs injection of injection, injection freeze-dried powder, big infusion or primary infusion；
Preferably, described pharmaceutical composition is solid orally ingestible, liquid oral medicine or injection；
It is further preferred that described pharmaceutical composition is tablet, dispersible tablet, enteric coatel tablets, chewable tablets, oral disintegrating tablet, capsule, sugar
Clothing agent, granule, dry powder doses, oral solution, the small liquid drugs injection of injection, injection freeze-dried powder, big infusion or primary infusion.
Beneficial effect of the present invention：The present invention provides a kind of new opplication of dihydroartemisinine.Our research indicate that double hydrogen
Qinghaosu can be obviously improved glomerulus oedema, bleeding and the inflammatory symptoms that the acute injury of kidney of pyemia induction occurs, specifically
, the dihydroartemisinine processing of low dosage does not make a significant impact the growth characteristics of glomerular endothelial cells, but energy
It is excessive significantly to suppress glomerular endothelial cells permeability caused by tumor necrosis factor TNF-alpha；Further study showed that tumour
Necrosis factor TNF-alpha reduces expression of the connection albumen Occludin in glomerular endothelial cells, and dihydroartemisinine can raise
It is expressed.Therefore, our result indicate that dihydroartemisinine is reduced in glomerulus by raising the expression of Occludin albumen
The permeability of chrotoplast.
Our research indicate that dihydroartemisinine has the ability of the acute injury of kidney for the treatment of pyemia induction.Ours grinds
Studying carefully helps to more fully understand the mechanism for result above occur, in terms of tissue damage caused by pyemia have it is important answer face
Bed application value, at the same for dihydroartemisinine and other clinically safe artemisinin derivative opens new medicinal usage.
Brief description of the drawings
Figure 1A is mouse urinary albumin/creatinine ratio (n=6 after different disposal group and control group processing；**P<0.01)；
Figure 1B is kidney of mouse morphology picture after different disposal group and control group processing；
Fig. 2A is the overpass running of the murine glomerular inner hypophloeodal single-layer cell after different disposal group and control group processing；Figure
2B is that the murine glomerular inner hypophloeodal single-layer cell transwell permeabilities after different disposal group and control group processing detect (n=
6；**P<0.01)；
Fig. 3 A are that the double dye methods of AnnexinV/PI detect the murine glomerular endothelial cell fluidic cell figure after DHA processing；Figure
3B is the column result figure (n=4 of Fig. 3 A；n.s.non-significant)；Fig. 3 C detect DHA processing for trypan exclusion stain
Murine glomerular endotheliocyte viability (n=4, n.s., non-significant) afterwards；
Fig. 4 A are that the murine glomerular endothelial cell Occludin protein immunizations after different disposal group and control group processing are glimmering
Light figure；Fig. 4 B are the murine glomerular endothelial cell Occludin protein immunoblots after different disposal group and control group processing
Figure, wherein GAPDH is as internal reference albumen；Fig. 4 C are optical densitometric method to the murine glomerular after different disposal group and control group processing
Endothelial cell Occludin expressing quantities detect (n=4；n.s.,non-significant；**P<0.01).
Embodiment
It is noted that described further below is all illustrative, it is intended to provides further instruction to the application.It is unless another
Indicate, all technical and scientific terms used herein has usual with the application person of an ordinary skill in the technical field
The identical meanings of understanding.
It should be noted that term used herein above is merely to describe embodiment, and be not intended to restricted root
According to the illustrative embodiments of the application.As used herein, unless the context clearly indicates otherwise, otherwise singulative
It is also intended to include plural form, additionally, it should be understood that, when in the present specification using term "comprising" and/or " bag
Include " when, it indicates existing characteristics, step, operation, device, component and/or combinations thereof.
With reference to instantiation, the present invention is further illustrated, and following instance is not right merely to the explanation present invention
Its content is defined.If the experiment actual conditions being not specified in embodiment, usually according to normal condition, or it is public according to reagent
The recommended condition of department；Reagent used, consumptive material etc., are commercially available unless otherwise specified in following embodiments.
Greatly threaten and choose as it was previously stated, the acute injury of kidney of pyemia induction forms human health and economic development
War.
In a kind of exemplary embodiment of the present invention, there is provided dihydroartemisinine is preparing the acute for the treatment of pyemia induction
Application in injury of kidney medicine；Dihydroartemisinine can be obviously improved the glomerulus occurred in the acute injury of kidney of pyemia induction
Oedema, bleeding and inflammatory symptoms；
In the still another embodiment of the present invention, there is provided dihydroartemisinine is preparing suppression TNF (Tumor Necrosis Factor) alpha
Application in the excessive medicine of caused glomerular endothelial cells (HRGECs) permeability；
In the still another embodiment of the present invention, there is provided dihydroartemisinine is raised in the case where preparing inflammatory conditions
Occludin protein expressions are to reduce the application in the excessive medicine of glomerular endothelial cells permeability；
Wherein, the inflammatory conditions promotive factor includes TNF (Tumor Necrosis Factor) alpha；
The present invention still another embodiment in, the drug medication valid density for 25 μM and more than, it is described effectively
Concentration is the concentration for the internal medicine for reaching lesion；
In the still another embodiment of the present invention, the medicine also pharmaceutically or in bromatology can comprising one or more
The auxiliary material of receiving.Auxiliary material used can be solid-state or liquid.The preparation of solid-state form include pulvis, tablet, discrete particles, capsule,
Pill and suppository.Pulvis and tablet can include about the active ingredient of 0.1% to about 99.9%.Appropriate solid adjuvant material can be carbon
Sour magnesium, magnesium stearate, talcum powder, sugar or lactose.Tablet, pulvis, pill and capsule are suitable for solid dosage for oral use.Liquid
The preparation of state form includes solution, suspension and lotion, and embodiment is molten for parenteral injection aqueous solution or water-propane diols
Liquid, or the oral administration solution of addition sweetener and contrast agent.In addition, it may also be fabricated which the small liquid drugs injection of injection, injection freeze-dried powder, big
Infusion or primary infusion；
In the still another embodiment of the present invention, described pharmaceutical composition is solid orally ingestible, liquid oral medicine
Or injection；
The present invention still another embodiment in, described pharmaceutical composition for tablet, dispersible tablet, enteric coatel tablets, chewable tablets,
It is oral disintegrating tablet, capsule, sugar-coat agent, granule, dry powder doses, oral solution, the small liquid drugs injection of injection, injection freeze-dried powder, big defeated
Liquid or primary infusion.
Below by embodiment, the operation to the present invention, is described in further detail.
Embodiment
Materials and methods
Animal
6 week old C57BL/6J mouse (weight 22-25g), buy from Beijing Vital River Experimental Animals Technology Co., Ltd..
LPS (derives from Escherichia coli 055:B5) bought from U.S. Sigma Aldrich public affairs with dihydroartemisinine DHA
Department.Injection LPS (20mg/kg), establishes sepsis model in mouse peritoneal.After injection 1 it is small when, every intragastric administration on mice gives DHA
(50mg/kg, DHA are dissolved in PBS).24 it is small when after, collect the urine during this, kill mouse and obtain kidney.All programs are equal
Carried out in accordance with the guide of Animal Experimental Ethical examination board of Shandong University.
Urinary albumin-creatinine ratio ratio (UACR)
Urine specimen 2000g, 4 DEG C centrifuge 5 minutes, take supernatant be used for detect.Immune ratio is based on using commercial kit
Turbid method principle detects urinary albumin.Urine creatinine carries out colorimetric analysis using the method for the reports such as Jaffe.
Hematoxylin eosin staining
Mouse Kidney is fixed with 4% paraformaldehyde, is embedded on dry ice into U.S.'s oriental cherry board freezing microtome section embedding medium.By tissue
5 microns of slabs are cut into, are dyed 5 minutes with 1% hematoxylin.After washing, section is immersed in 1% hydrochloric acid-ethanol solution
In, after being washed with distillation, then with 0.5% eosin stains 15 seconds.Section is used after graded ethanol dehydration and dimethylbenzene are transparent
Resinene mounting.The morphological change of nephridial tissue is observed under an optical microscope, and utilizes BX-51 fiber camera systems
(Olympus Corporation, Tokyo, Japan) takes pictures.
Cell culture
Glomerular endothelial cells (HRGECs) are purchased from U.S. ScienCell Research laboratories.Culture is cultivated in DMEM
In liquid, 10% hyclone, 100IU/ml penicillin and 100 μ g/ml streptomysins are with the addition of.It is 37 DEG C to cultivate incubator condition,
5%CO2.TNF-α purchase acts on final concentration of on glomerular endothelial cells from Miltenyi Biotec companies of Germany
20ng/ml。
Fluorescein isothiocynate-dextran (FITC-dextran) Transwell cells Matrigel
Transwell is inserted in 24 hole Transwell cells, and glomerular endothelial cells (1 × 105cells) kind is existed
Transwell tops, 24 small durations of culture to fusion.It is then small with the processing 24 of 20ng/ml TNF-α after being handled with 25 μM of DHA
When, with Hepes wash buffers, 1mg fluorescein isothiocynates-dextrose (FITC-dextran) is dissolved in 1ml PBS,
It is added in cell top.4 it is small when after, from cell bottom collection sample, detected using sepectrophotofluorometer, excitation wavelength
485nm, wavelength of transmitted light 520nm.Electronic cell-matrix impedance sensing analysis (ECIS)
With across the glomerular endothelial cells resistance of ECIS technology for detection.8 orifice plates analyzed for ECIS are spread by upper one first
Layer fibronectin.Then it is long to Fusion Strain directly in top of electrodes kind last layer HRGECs cells.With DHA or/and
After TNF α processing, alternating current acts on the electrode, and resistance is just recorded.
Annexin V-FITC/PI are analyzed and cell survival rate detection
Utilize Annexin V-FITC and the double transfection reagent box detection HRGECs apoptosis of propidium iodide (PI).First by cell from
The heart, is washed twice with PBS.Then, cell precipitation is suspended into individual cells with combination buffer (binding buffer).Take 1
× 106 cells are dyed 3 minutes under the conditions of lucifuge with Annexin V-FITC (0.025%), PI (20 μ g/mL) dyeing 10
Minute.The cell of stained positive with FACSAria II flow cytomeries (BD Biosciences, San Jose, CA,
USA).With FACS Diva collections and analysis software data.Cell viability in 96 orifice plates is detected with trypan exclusion stain.Wash
After cell, it is incubated 2 minutes with 0.05% pancreatin at 37 DEG C.After the completion of digestion, cell suspension presses 1:1 ratio adds 0.4%
Expect blue (0.4g trypan blues are dissolved in 100ml 0.9%NaCl), calculate the ratio shared by the cell not being colored.
Western Blotting
Extract HRGEC total proteins.Protein concentration is surveyed with BCA methods.Equal protein (40 μ g) carries out lauryl sodium sulfate and gathers
Acrylamide gel electrophoresis, concentration of polyacrylamide 10%, by protein delivery to pvdf membrane after electrophoresis.With 2.5%
When BSA room temperatures closing 2 is small.Then 4 degree of antibody (1 for being incubated anti-occludin are stayed overnight:1000；Abcam,Cambridge,MA,
USA).After washing 3 times with TBST solution, with the goat anti-rabbit antibody (1 for being combined with horseradish peroxidase:6000) when incubation 1 is small.
Developed the color with ECL chemical luminescence reagent kits.With ImageJ software analysis gray values.
Immunofluorescence
By HRGECs kinds in the glass slide of coating fibronectin, with 25 μM of DHA handle 24 it is small when.Suck culture
Liquid, is fixed after washing cell with PBS with 4% paraformaldehyde, continues to wash 3 times, totally 15 minutes with PBS.With the one of anti-human occludin
Anti- 4 spend night incubated cell (1:500, Abcam) secondary antibody (1, marked with rhodamine:200) it is incubated 30 minutes.Glass slide is existed
Observe and take pictures under Olympus LCX100 imaging systems, wavelength of transmitted light 546nm.
Experimental result
1.DHA improves the acute renal injury in mice of LPS inductions
In order to inquire into influences of the DHA for acute injury of kidney caused by pyemia, we establish septicopyemia with LPS processing mouse
Disease model.UACR is the evaluation criterion of urinary albumin excretion ratio, therefore we have detected lps injection mouse with DHA before and after the processing
UACR.The result shows that lps injection mouse UACR is significantly higher than control group mice.Reduced after DHA processing by LPS up-regulations
UACR levels (P<0.01, Figure 1A).H-E dyeing is carried out to kidney of mouse, the results showed that, in the independent treatment groups of DHA, glomerulus
Normally.There is serious glomerular injury with bleeding, oedema and inflammatory cell infiltration in lps injection group.After DHA processing, maintain
The glomerular permeability of lps injection group, and oedema obtains part improves (Figure 1B).Result above shows that DHA is alleviated
Murine glomerular caused by LPS damages.
It is excessive that 2.DHA reduces HRGEC permeabilities caused by TNF-α
For further influences of the clear and definite DHA for glomerular endothelial cells permeability, we use electronic cell-matrix
Impedance sensing analysis system have detected the overpass running (TEER) of individual layer HRGECs.It was found that significantly dropped after TNF-α processing
The low TEER of HRGECs, and DHA has then significantly reversed this change (Fig. 2A).Next carried out using FITC- dextrans
The detection of transwell permeabilities also obtain similar result.It is penetrating that DHA significantly reduces the HRGECs as caused by TNF-α
Excessive (the P of property<0.01, Fig. 2 B).In two above experiment, individually processing does not change the penetrating of HRGECs cell monolayers to DHA
Property (P=0.22, P=0.14, respectively).In general, our result indicate that, DHA is improved to be caused by TNF-α
HRGECs permeabilities it is excessive.
Then, to murine glomerular endothelial cell apoptosis shadow after we are handled using the double dye method detection DHA of AnnexinV/PI
Ring, as a result such as Fig. 3 A, shown in B, compared with control group, murine glomerular endothelial cell incidence after being handled using DHA with it is right
According to group compare no significant changes (P=0.11), trypan blue exclusion experiment in, as shown in Figure 3 C, DHA handle after murine glomerular
Endotheliocyte viability and control group are almost identical (P=0.25)；Therefore, DHA can be reduced effectively because of the Mouse Kidney of TNF-α induction
Bead endothelial cell permeability raises, while can't trigger murine glomerular endothelial cell apoptosis or influence cell viability.
3. in HRGECs, DHA maintains the expression of Occludin albumen
Occludin albumen is extremely important for the integrality and vasopermeability for maintaining endothelial cell barrier.Therefore,
It has detected influences of the DHA for HRGECs occludin protein expressions.Immunofluorescence experiment shows, is reduced after TNF-α processing
The fluorescence intensity (Fig. 4 A) of occludin albumen on cytoplasma membrane, and 25 μM of DHA pretreatments have reversed TNF-α induction pair
Effect (the P of occludin albumen<0.01), individually processing does not influence (figure to DHA on the occludin protein levels of HRGECs
4B, C), these results indicate that DHA maintains the expression of occludin under inflammatory conditions.
To sum up, we are such as drawn a conclusion：1.DHA alleviates the acute injury of kidney of LPS inductions in mouse model；
The HRGECs permeabilities that 2.DHA reduces TNF-α induction are excessive；3. in HRGECs, DHA maintains the expression of occludin.
It is well known that the acute injury of kidney of pyemia induction is a principal element of ICU critical patients death.We
Mouse is handled to simulate pyemia using LPS, it turns out that, DHA alleviates the injury of kidney of LPS inductions.25 μM of DHA processing pair
The growth characteristics of HRGECs do not influence, but it is excessive significantly to suppress permeability caused by TNF-α.Our experiment contributes to
More fully understand the mechanism of result above occur, there is clinical value in terms of tissue damage caused by pyemia, DHA and
Clinically safe artemisinin derivative is likely to become the medicine for the treatment of pyemia damage for other.
The foregoing is merely the preferred embodiment of the application, the application is not limited to, for the skill of this area
For art personnel, the application can have various modifications and variations.It is all within spirit herein and principle, made any repair
Change, equivalent substitution, improvement etc., should be included within the protection domain of the application.
Claims (10)
1. application of the dihydroartemisinine in the acute injury of kidney medicine for preparing treatment pyemia induction.
2. application as claimed in claim 1, it is characterised in that the dihydroartemisinine can be obviously improved the urgency of pyemia induction
Glomerulus oedema, bleeding and the inflammatory symptoms occurred in property injury of kidney.
3. dihydroartemisinine is preparing glomerular endothelial cells (HRGECs) permeability caused by suppression TNF (Tumor Necrosis Factor) alpha
Application in excessive medicine.
It is penetrating to reduce glomerular endothelial cells that 4. dihydroartemisinine raises Occludin protein expressions in the case where preparing inflammatory conditions
Application in the excessive medicine of property.
5. application as claimed in claim 4, it is characterised in that inflammatory conditions promotive factor includes TNF (Tumor Necrosis Factor) alpha.
6. any one of the claim 1-5 applications, it is characterised in that the drug medication valid density for 25 μM and more than.
7. applied as described in claim any one of 1-6, it is characterised in that the medicine also comprising it is one or more pharmaceutically or
Acceptable auxiliary material in bromatology.
8. application as claimed in claim 7, it is characterised in that auxiliary material used in the medicine is solid-state or liquid.
9. application as claimed in claim 8, it is characterised in that the preparation of solid-state form includes pulvis, tablet, discrete particles, glue
Capsule, pill and suppository；Preferably, pulvis and tablet include the active ingredient of about 0.1% to about 99.9%；Solid adjuvant material is selected from carbon
Sour magnesium, magnesium stearate, talcum powder, sugar or lactose；
The preparation of liquid form includes solution, suspension and lotion, it is preferred that liquid for parenteral injection aqueous solution or water-
Propylene glycol solution, or the oral administration solution of addition sweetener and contrast agent.
10. application as claimed in claim 8, it is characterised in that the small liquid drugs injection of injection, injection freeze-dried powder is made in the medicine
Pin, big infusion or primary infusion.
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| CN201711212287.4A CN107982250A (en) | 2017-11-28 | 2017-11-28 | Application of the dihydroartemisinine in the acute injury of kidney medicine for the treatment of pyemia induction |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111617070A (en) * | 2019-06-11 | 2020-09-04 | 中国农业大学 | Application of dihydroartemisinin in preparation of medicine for treating inflammation caused by streptococcus suis virulence protein |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2014090306A1 (en) * | 2012-12-12 | 2014-06-19 | Queen Mary & Westfield College, University Of London | Artemisinin and its derivatives for use in the treatment of kidney disease |
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2017
- 2017-11-28 CN CN201711212287.4A patent/CN107982250A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014090306A1 (en) * | 2012-12-12 | 2014-06-19 | Queen Mary & Westfield College, University Of London | Artemisinin and its derivatives for use in the treatment of kidney disease |
Non-Patent Citations (1)
| Title |
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| 吴苹等: "小鼠肾炎模型的制备及双氢青蒿素对其炎症因子释放的影响", 《华西医学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111617070A (en) * | 2019-06-11 | 2020-09-04 | 中国农业大学 | Application of dihydroartemisinin in preparation of medicine for treating inflammation caused by streptococcus suis virulence protein |
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Application publication date: 20180504 |