CN103494793A - Application of 3,4,5,3',4',5'-hexamethoxy-trans-stilbene in preparing angiogenesis promoting drugs - Google Patents
Application of 3,4,5,3',4',5'-hexamethoxy-trans-stilbene in preparing angiogenesis promoting drugs Download PDFInfo
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Abstract
The invention discloses application of 3,4,5,3',4',5'-hexamethoxy-trans-stilbene in preparing angiogenesis promoting drugs, wherein the effective concentration of the application of the 3,4,5,3',4',5'-hexamethoxy-trans-stilbene in preparing angiogenesis promoting drugs is 40-80 micro M. According to the invention, the 3,4,5,3',4',5'-hexamethoxy-trans-stilbene is sufficiently proved to be able to effectively promote angiogenesis in vivo and in vitro through a scratching migration experiment, an in-vitro angiogenesis detection experiment, an ex-vivo angiogenesis detection experiment, an in-vivo chick chorioallantoic membrane angiogenesis detection experiment and an in-vivo mice Matrigel embolism angiogenesis detection experiment. Furthermore, the 3,4,5,3',4',5'-hexamethoxy-trans-stilbene is proved to have enormous application and development prospect in preparing angiogenesis promoting and ischemic disease treating drugs.
Description
Technical field
The present invention relates to a kind of application of resveratrol methoxy derivatives, especially relate to a kind of 3,4,5,3 ', 4 ', the application of 5 '-hexa methoxy trans stilbene in preparing angiogenesis promoting medicine.
Background technology
3,4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene structural formula is:
3,4,5,3 ', 4 ', the molecular formula of 5 '-hexa methoxy trans stilbene is C
20h
24o
6, molecular weight is 360.4, character is off-white color crystalloid powder.3,4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene is called again E-3,4,5,3', 4', 5'-hexa methoxy stilbene.
Resveratrol, chemical name is Resvertrol, belongs to the natural polyphenol compounds.Large quantity research confirms: resveratrol has multiple pharmacodynamics effect as effects such as antitumor, defying age, antiinflammatory, nerve and cardiovascular protections.But resveratrol character is unstable, and bioavailability is low, very easily by metabolism and discharge, limited its pharmacologic activity in vivo.In recent years, people's chemosynthesis many Verakanol derivatives, further research finds that most of Verakanol derivative all is being better than resveratrol aspect stability, pharmacologically active and targeting.
According to retrieval, about resveratrol and derivant thereof, relevant patent literature is arranged at present.For example: 1, application number is 201010591625.1, name is called the patent of invention of " new medical use of resveratrol and derivant thereof ", this patent discloses resveratrol and derivant (RV01 thereof, RV02, RV32) in the preparation periphery immunologic hypofunction health food that causes of anti-excessive drinking and the new purposes of pharmaceutical preparations.2, application number is 200610134004.4, name is called the application for a patent for invention of " Verakanol derivative and its production and use ", this patent discloses respectively with 3,5-dialkoxy-4 '-hydroxy stibene, hydroxy benzaldehyde are that raw material has prepared compound (I), simple for process.Its pharmaceutically acceptable alkali and officinal salt have good prevention and treatment to various diseases such as tumor, cardiovascular disease, inflammation, its officinal salt, activity obviously is better than resveratrol and Pterostilbene, and salify can improve the stability of resveratrol and Pterostilbene and can improve its pharmacokinetic parameter.3, application number is 201010590982.6, name is called " a kind of Verakanol derivative and its preparation method and application ", it is 2-pi-allyl-5-[(E that this patent discloses a kind of derivant)-2-(3-pi-allyl-4-hydroxy phenyl) vinyl] benzene-1, the 3-diphenol has the architectural feature similar to resveratrol, and its anti-tumor activity is compared obvious raising with resveratrol; The growth of inhibition tumor cell significantly, can have a wide range of applications preparing on antitumor drug.
At present, the hexamethyl derivant 3,4,5,3 ', 4 ' of people to resveratrol, the research of 5 '-hexa methoxy trans stilbene is still rare.Through authoritative institution's retrieval, look into newly, 3,4,5,3 ', 4 ', effect and the relevant pharmacological research application thereof of 5 '-hexa methoxy trans stilbene aspect Angiogensis, there is not yet report at present both at home and abroad.
Summary of the invention
The technical problem to be solved in the present invention is: for the deficiencies in the prior art part, the invention provides a kind of 3,4,5,3 ', 4 ', the application of 5 '-hexa methoxy trans stilbene in preparing angiogenesis promoting medicine.
In order to address the above problem, the technical solution used in the present invention:
The invention provides a kind of 3,4,5,3 ', 4 ', the application of 5 '-hexa methoxy trans stilbene in preparing angiogenesis promoting medicine.
According to above-mentioned 3,4,5,3 ', 4 ', the application of 5 '-hexa methoxy trans stilbene in preparing angiogenesis promoting medicine, described 3,4,5,3 ', 4 ', the valid density that 5 '-hexa methoxy trans stilbene is applied in preparing angiogenesis promoting medicine is that 40～80 μ M of μ M(unit refer to μ mol/L).
experimental results show that:
Below in conjunction with 3,4,5,3 ', 4 ', the pharmacological evaluation of 5 '-hexa methoxy trans stilbene and result, illustrate 3,4,5,3 ', 4 ', the effect of 5 '-hexa methoxy trans stilbene in preparing angiogenesis promoting medicine.
The preparation of vascular endothelial cell: cultivate vascular endothelial cell with conventional method, choose growth conditions good and standby in the vascular endothelial cell of exponential phase.
In conjunction with the method for Celluar and Molecular Biology, test as follows, to observe 3,4,5,3 ', 4 ', the impact of 5 '-hexa methoxy trans stilbene on angiogenesis.
Experiment 1, scuffing migration experiment detect 3,4,5,3 ', 4 ', the impact of 5 '-hexa methoxy trans stilbene on migration of vascular endothelial cells:
Vascular endothelial cell is inoculated in 24 porocyte culture plates, treats that cell grows to the fusion state, at the standardized cut in center bottom, hole, the solvent control group is set: add the dimethyl sulfoxide (DMSO) of 80 μ M to process cell 24 or 48 hours; Experimental group: add 3,4,5,3 ', 4 ' of 5～80 μ M, 5 '-hexa methoxy trans stilbene is processed respectively cell 24 or 48 hours.By inverted phase contrast microscope observation of cell transition state computation migration distance.
Experimental result shows: 3,4,5 of 40～80 μ M, 3 ', 4 ', 5 '-hexa methoxy trans stilbene is processed vascular endothelial cell 24 hours, 3 of 10～80 μ M, 4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene is processed vascular endothelial cell 48 hours, obviously the induction of vascular endothelial cell migration.Wherein, 3,4,5,3 ', 4 ' of 40～80 μ M, 5 '-hexa methoxy trans stilbene is processed vascular endothelial cell 48 hours, promotes extremely significantly migration of vascular endothelial cells (referring to attached Fig. 1 and 2).
Experiment 2, extracorporeal blood vessel generate and detect:
Vascular endothelial cell is inoculated in the 96 porocyte culture plates that are coated with Matrigel, after cell attachment, the solvent control group is set: add the dimethyl sulfoxide (DMSO) of 80 μ M to process cell 12 hours; Experimental group: add 3,4,5,3 ', 4 ' of 40 or 80 μ M, 5 '-hexa methoxy trans stilbene is processed respectively cell 12 hours.Observe the angiogenesis situation of vascular endothelial cell on Matrigel with inverted phase contrast microscope.With matched group, compare, 3,4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene significantly promotes vascular endothelial cell to form the capillary structure of tube chamber shape on Matrigel, and branch point increases.
Experimental result shows: during extracorporeal blood vessel generates and detects, and 3,4,5,3 ', 4 ' of 40 or 80 μ M, 5 '-hexa methoxy trans stilbene can significantly promote vascular endothelial cell to become blood vessel (referring to accompanying drawing 3).
In experiment 3, halfbody, angiogenesis detects:
Choose at random the 6-8 Wistar rat in age in week, be divided into three groups, 10 every group.Get its thoracic aorta under aseptic condition, be cut into the arterial ring of 1mm left and right, be positioned in the 96 porocyte culture plates that are coated with Matrigel, then with the coated arterial ring of 60 μ L Matrigel.The solvent control group is set: add the dimethyl sulfoxide (DMSO) of 80 μ M to process arterial ring 7 days; Experimental group: add 3,4,5,3 ', 4 ' of 40 or 80 μ M, 5 '-hexa methoxy trans stilbene is processed respectively arterial ring 7 days.Observe arterial ring new vessels branch situation with inverted phase contrast microscope.With matched group, compare, 3,4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene significantly increases arterial ring new vessels number of branches and length on every side.
Experimental result shows: during in halfbody, angiogenesis detects, and 3,4,5,3 ', 4 ' of 40 or 80 μ M, 5 '-hexa methoxy trans stilbene can significantly promote arterial ring peripheral vessels newborn (referring to accompanying drawing 4).
In experiment 4, body, the chick chorioallantoic membrane angiogenesis detects:
Choose the egg of normal fertilization, be divided into three groups, 20 every group.The solvent control group is set: the filter membrane sheet that will to be soaked with 50 μ L, concentration be 80 μ M DMSO is placed on the chick chorioallantoic membrane surface; Experimental group: will be soaked with 50 μ L, concentration is 3,4,5,3 ', 4 ' of 40 μ M or 80 μ M, the filter membrane sheet of 5 '-hexa methoxy trans stilbene is placed on the chick chorioallantoic membrane surface, with Parafilm, seals afterwards; Egg is put into to 37 ℃, hatch in the constant incubator of relative humidity 80% 3 days.After hatching end, the chick chorioallantoic membrane 20 minutes of filter membrane is arranged by 4% paraformaldehyde fixed placement, observe and take pictures and count.Compare with matched group, load 3,4,5,3 ', 4 ', on the filter membrane sheet of 5 '-hexa methoxy trans stilbene, new vessels is intensive dendroid bifurcated, outwards the multistage minute blood vessel of branch.
Experimental result shows: during angiogenesis detects in vivo, and 3,4,5,3 ', 4 ' of 40 or 80 μ M, 5 '-hexa methoxy trans stilbene can significantly promote chick chorioallantoic membrane angiogenesis (referring to accompanying drawing 5 and 6).
In experiment 5, body, mice Matrigel vascular embolization generates and detects:
Choose at random the C57BL/6 mice in 8 week age, be divided into three groups, 10 every group; Add 3,4,5,3 ', 4 ' under 4 ℃ of environment in 500 μ L Matrigel, 5 '-hexa methoxy trans stilbene, making its final concentration is 40 μ M or 80 μ M, is set to experimental group.The DMSO that to choose final concentration be 80 μ M is set to matched group.It is subcutaneous that the Matrigel mixed solution that 500 μ L are prepared is injected into mice.The normal raising 7 days, take out its subcutaneous Matrigel thromboembolism, takes pictures.Matched group Matrigel thromboembolism is transparence, and meaning does not have or extremely a small amount of angiogenesis; And the Matrigel thromboembolism that 3,4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene of 40～80 μ M adds is secretly blood red, and include a lot of new vesselses.
Experimental result shows: during angiogenesis detects in vivo, and 3,4,5,3 ', 4 ' of 40 or 80 μ M, 5 '-hexa methoxy trans stilbene can obviously promote the angiogenesis (referring to accompanying drawing 7) in mice Matrigel thromboembolism.
Above-mentioned experimental data statistical procedures:
Result means with mean+SD.Warp
tcheck,
pbe considered as significant difference at<0.05 o'clock.
By above-mentioned experiment and result thereof, can draw the following conclusions:
3,4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene concentration when 40 or 80 μ M, external all Angiogensis effectively in vivo.Proved 3,4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene has very large application and development prospect in preparing Angiogensis and treatment ischemic diseases medicine.
Experiment of the present invention and result thereof have proved 3,4,5,3 ', 4 ', and 5 '-hexa methoxy trans stilbene promotes, in angiogenesis drug, remarkable effect to be arranged in preparation, for preparing angiogenesis promoting medicine and novel ischemic diseases drug development provides tempting prospect.
the accompanying drawing explanation
Fig. 1: be solvent control group and 3,4,5 under inverted phase contrast microscope, 3 ', 4 ', 5 '-hexa methoxy trans stilbene experimental group is processed the aspect graph of migration of vascular endothelial cells after 0,24 and 48 hour.
In Fig. 1: A(0 hour), G(24 hour), M(48 hour) be the solvent control group; B(0 hour), H(24 hour), N(48 hour) be 3,4,5,3 ', 4 ' of 5 μ M, 5 '-hexa methoxy trans stilbene experimental group; C(0 hour), I(24 hour), O(48 hour) be 3,4,5,3 ', 4 ' of 10 μ M, 5 '-hexa methoxy trans stilbene experimental group; D(0 hour), J(24 hour), P(48 hour) be 3,4,5,3 ', 4 ' of 20 μ M, 5 '-hexa methoxy trans stilbene experimental group; E(0 hour), K(24 hour), Q(48 hour) be 3,4,5,3 ', 4 ' of 40 μ M, 5 '-hexa methoxy trans stilbene experimental group; F(0 hour), L(24 hour), R(48 hour) be 3,4,5,3 ', 4 ' of 80 μ M, 5 '-hexa methoxy trans stilbene experimental group.
Fig. 2: be the migration of vascular endothelial cells rate.
Fig. 3: be under inverted phase contrast microscope, in being covered with the 96 porocyte culture plates of Matrigel, solvent control group and 3,4,5,3 ', 4 ', the vascular endothelial cell of 5 '-hexa methoxy trans stilbene experimental group after 12 hours becomes the aspect graph of blood vessel.
In Fig. 3: A(12 hour) be the solvent control group; B(12 hour) be 3,4,5,3 ', 4 ' of 40 μ M, 5 '-hexa methoxy trans stilbene experimental group; C(12 hour) be 3,4,5,3 ', 4 ' of 80 μ M, 5 '-hexa methoxy trans stilbene experimental group.
Fig. 4: be under inverted phase contrast microscope, solvent control group and 3,4,5,3 ', 4 ', the aspect graph of 5 '-hexa methoxy trans stilbene experimental group angeogenesis in rat aorta ring.
In Fig. 4: A is the solvent control group; B is 3,4,5,3 ', 4 ' of 40 μ M, 5 '-hexa methoxy trans stilbene experimental group; C is 3,4,5,3 ', 4 ' of 80 μ M, 5 '-hexa methoxy trans stilbene experimental group.
Fig. 5: be the solvent control group and 3,4,5 that digital camera is taken, 3 ', 4 ', the chick chorioallantoic membrane that 5 '-hexa methoxy trans stilbene experimental group is processed, detect the aspect graph of its new vessels.
In Fig. 5: A is the solvent control group; B is 3,4,5,3 ', 4 ' of 40 μ M, 5 '-hexa methoxy trans stilbene experimental group; C is 3,4,5,3 ', 4 ' of 80 μ M, 5 '-hexa methoxy trans stilbene experimental group.
Fig. 6: chick chorioallantoic membrane angiogenesis number statistical figure.
Fig. 7: be the solvent control group and 3,4,5 that digital camera is taken, 3 ', 4 ', the subcutaneous Matrigel thromboembolism of mice that 5 '-hexa methoxy trans stilbene experimental group is processed, observe the wherein aspect graph of new vessels.
In Fig. 7: A is the solvent control group; B is 3,4,5,3 ', 4 ' of 40 μ M, 5 '-hexa methoxy trans stilbene experimental group; C is 3,4,5,3 ', 4 ' of 80 μ M, 5 '-hexa methoxy trans stilbene experimental group.
specific embodiments:
Following examples only, for further illustrating the present invention, do not limit content of the present invention.
Embodiment 1:3,4,5,3 ', 4 ', the application of 5 '-hexa methoxy trans stilbene in preparing angiogenesis promoting medicine:
The preparation of vascular endothelial cell: cultivate vascular endothelial cell with conventional method, choose growth conditions good and standby in the vascular endothelial cell of exponential phase.
Vascular endothelial cell is inoculated in 24 porocyte culture plates, add respectively 1mL MCDB131 cell culture fluid, treat that cell grows to the fusion state, the standardized cut of centre in the bottom, hole, the old culture fluid in each hole is abandoned in suction, 1 * PBS(phosphate buffer) clean one time, add the DMSO(matched group that concentration is 80 μ M respectively in each hole) and 5, 10, 20, 40, 3 of 80 μ M, 4, 5, 3 ', 4 ', 5 '-hexa methoxy trans stilbene (experimental group) is processed 24 and 48 hours, observe migration of vascular endothelial cells form computation migration distance with inverted phase contrast microscope.
Experimental result shows: 3,4,5 of 40～80 μ M, 3 ', 4 ', 5 '-hexa methoxy trans stilbene is processed vascular endothelial cell 24 hours, 3 of 10～80 μ M, 4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene is processed vascular endothelial cell 48 hours, obviously the induction of vascular endothelial cell migration.Wherein, 3,4,5,3 ', 4 ' of 40～80 μ M, 5 '-hexa methoxy trans stilbene is processed vascular endothelial cell 48 hours, promotes extremely significantly migration of vascular endothelial cells (referring to attached Fig. 1 and 2).
Embodiment 2:3,4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene promotes the application in angiogenesis drug in preparation:
The preparation of vascular endothelial cell: cultivate vascular endothelial cell with conventional method, choose growth conditions good and standby in the vascular endothelial cell of exponential phase.
Do not contain the Matrigel of somatomedin in 96 porocyte culture plates of 4 ℃ of pre-coolings, every hole adds 30 μ L, and plate is placed in to 37 ℃ of incubators 1 hour, and Matrigel is fully solidified.By vascular endothelial cell with 4 * 10
4density be inoculated in the 96 culture hole Tissue Culture Plates of coated good Matrigel, be placed in 37 ℃, CO
2in incubator, hatch 1 hour.After cell attachment, the every hole of matched group adds the DMSO of 100 μ L concentration 80 μ M, and the every hole of experimental group adds 3,4,5,3 ', 4 ' of 100 μ L concentration 40 μ M or 80 μ M, and 5 '-hexa methoxy trans stilbene is processed 12 hours.Observe the one-tenth blood vessel situation of vascular endothelial cell on Matrigel under inverted phase contrast microscope.
Experimental result shows: during angiogenesis detects in vitro, and 33,4,5,3 ', 4 ' of 40 or 80 μ M, 5 '-hexa methoxy trans stilbene has significant short vascular endothelial cell and becomes blood vessel function (referring to accompanying drawing 3).
Embodiment 3:3,4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene promotes the application in angiogenesis drug in preparation:
Do not contain the Matrigel of somatomedin in 96 porocyte culture plates of 4 ℃ of pre-coolings, every hole adds 30 μ L, Tissue Culture Plate is placed in to 37 ℃, CO
2incubator 1 hour, fully solidify Matrigel.Choose at random the 6-8 Wistar rat in age in week, be divided into three groups, 10 every group.Get its thoracic aorta under aseptic condition, clean up with 1 * PBS, be cut into the arterial ring of 1mm left and right, be positioned in the 96 porocyte culture plates that are coated with Matrigel, then, with 60 μ L Matrigel parcel arterial rings, Tissue Culture Plate is placed in to 37 ℃, CO
2incubator 1 hour, solidify Matrigel, fixedly arterial ring.The every hole of matched group adds the DMSO of 100 μ L concentration 80 μ M, and the every hole of experimental group adds 3,4,5,3 ', 4 ' of 100 μ L concentration 40 μ M or 80 μ M, and 5 '-hexa methoxy trans stilbene is processed, and within every two days, changes one time fresh medium, coprocessing 7 days.After finishing, processing observes arterial ring new vessels branch situation on every side with inverted phase contrast microscope.
Experimental result shows: during in halfbody, angiogenesis detects, and 3,4,5,3 ', 4 ' of 40 or 80 μ M, 5 '-hexa methoxy trans stilbene can significantly promote arterial ring peripheral vessels newborn (referring to accompanying drawing 4).
Embodiment 4:3,4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene promotes the application in angiogenesis drug in preparation:
Choose the egg of normal fertilization, be divided into three groups, 20 every group.By after egg sterilization, be placed in 37 ℃, the incubator of relative humidity 80% and hatch 4 days, between incubation period, tip one end of egg is placed downwards, and slight rotation is rocked several times by egg.After hatching end, the air bag face of egg is opened to a duck eye, carefully peel off eggshell and egg film with tweezers, to be soaked with the DMSO(solvent control group that 50 μ L, concentration are 80 μ M) and be soaked with 50 μ L, concentration is 3,4,5 of 40 μ M or 80 μ M, 3 ', the filter membrane sheet of 4 ', 5 '-hexa methoxy trans stilbene (experimental group) is placed on the chick chorioallantoic membrane surface, tries one's best away from the one-level trunk of chick chorioallantoic membrane in the residing position of filter membrane.With Parafilm, seal.Then egg is put into to 37 ℃, the constant incubator of relative humidity 80% and hatched 3 days, after hatching end, open air chamber, expose the chick chorioallantoic membrane after processing, with 4% paraformaldehyde, fix 20 minutes, digital camera is taken pictures and the new vessels on the filter membrane sheet is counted.
Experimental result shows: during angiogenesis detects in vivo, and 3,4,5,3 ', 4 ' of 40 or 80 μ M, 5 '-hexa methoxy trans stilbene can significantly promote chick chorioallantoic membrane angiogenesis (referring to accompanying drawing 5 and 6).
Embodiment 5:3,4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene promotes the application in angiogenesis drug in preparation:
Choose at random the C57BL/6 mice in 8 week age, be divided into three groups, 10 every group.Add 3,4,5,3 ', 4 ' under 4 ℃ of environment in 500 μ L Matrigel, 5 '-hexa methoxy trans stilbene, making its final concentration is 40 μ M or 80 μ M, is set to experimental group.The DMSO that to choose final concentration be 80 μ M is set to matched group.It is subcutaneous that the Matrigel mixed solution 500 μ L prepared with the 1ml disposable syringe is injected into mouse web portion.The Matrigel of injection solidifies in Mice Body.Normal raising mice 7 days, take out its subcutaneous Matrigel thromboembolism, and digital camera is taken pictures.
Experimental result shows: during angiogenesis detects in vivo, and 3,4,5,3 ', 4 ' of 40 or 80 μ M, 5 '-hexa methoxy trans stilbene can significantly promote the angiogenesis (referring to accompanying drawing 7) in mice Matrigel thromboembolism.
Can be proved 3,4 by experiment situation and concrete performance, 5,3 ', 4 ', 5 '-hexa methoxy trans stilbene has significant effect in preparing angiogenesis promoting medicine, 3,4,5,3 ', 4 ', 5 '-hexa methoxy trans stilbene can be applied in preparing angiogenesis promoting medicine.
Claims (2)
1. one kind 3,4,5,3 ', 4 ', the application of 5 '-hexa methoxy trans stilbene in preparing angiogenesis promoting medicine.
2. according to claim 13,4,5,3 ', 4 ', the application of 5 '-hexa methoxy trans stilbene in preparing angiogenesis promoting medicine is characterized in that: described 3,4,5,3 ', 4 ', the valid density that 5 '-hexa methoxy trans stilbene is applied in preparing angiogenesis promoting medicine is 40～80 μ M.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2007002973A2 (en) * | 2005-07-04 | 2007-01-11 | Medizinische Universität Wien | Use of stilbene derivatives for the production of medicaments for the treatment of solid tumours |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2007002973A2 (en) * | 2005-07-04 | 2007-01-11 | Medizinische Universität Wien | Use of stilbene derivatives for the production of medicaments for the treatment of solid tumours |
Non-Patent Citations (4)
| Title |
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| MAREK MURIAS, ET AL: "Resveratrol analogues as selective cyclooxygenase-2 inhibitors: synthesis and structure–activity relationship", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
| 张永强: "白藜芦醇诱导新生血管形成在小鼠缺血再灌注后的保护作用", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
| 陆冬晓，等: "白藜芦醇对糖尿病下肢缺血大鼠微血管新生的影响", 《广东医学》 * |
| 马宁，等: "白藜芦醇衍生物及类似物的药理活性与分析方法研究进展", 《中国新药杂志》 * |
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