CN109620835A - Asiaticosid is in the effect for promoting the survival of ischemic ultra long random flap - Google Patents
Asiaticosid is in the effect for promoting the survival of ischemic ultra long random flap Download PDFInfo
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- CN109620835A CN109620835A CN201910124342.7A CN201910124342A CN109620835A CN 109620835 A CN109620835 A CN 109620835A CN 201910124342 A CN201910124342 A CN 201910124342A CN 109620835 A CN109620835 A CN 109620835A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7024—Esters of saccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
The present invention relates to asiaticosids in the effect for promoting the survival of ischemic Survival of Random Flap.During promoting the survival of ischemic Survival of Random Flap by the way of stomach-filling, application method is daily oral cavity given low 40mg/kg, 7 days as one therapeutic course.It is drawn a conclusion by a large amount of zoopery, the survival surface ratio for using asiaticosid that can make flap significantly improves, and ischemic Survival of Random Flap can be promoted to survive well.
Description
Technical field
The present invention relates to the new application of asiaticosid, specifically asiaticosid is promoting the survival of ischemic ultra long random flap
Effect.
Background technique
Plastic surgery between " blood supply " always in " beauty " with having a contest, in this lasting campaign, plastic surgeon
Mission be exactly avoid flap " part " or it is " complete " necrosis.Although flap surgical technic has very big progress, facing
In bed application, flap necrosis is common complication in plastic surgery.Clinically, Survival of Random Flap is most basic as wound repair and most
Common operation method is clinically widely used in repair tissue defect because of its " flexibility ", " randomness ".However random skin
The hemoperfusion of valve is limited, the ischemic necrosis of flap distal end often occurs.How the blood supply situation of Survival of Random Flap distal end is improved
And tissue effectively reduces the ischemic necrosis that may occur, becomes core in Wound treating reparation and ask to the tolerance of ischemic
There is one of topic stronger social value, economic value and theory, practical studies to be worth.
Asiaticosid is mentioning from the herb of umbelliferae centella Centella asiatica (L.) Urban
Object, faint yellow to fallow powder are taken, its molecular formula is C48H78O16,Molecular weight is 959.12 g/mol, centella
Glycosides molecular structural formula is as follows:
Asiaticosid has odorless, bitter, slightly moist with drawing, and has promotion Wound Healing, for treating wound, performs the operation
Wound, burn, keloid and chorionitis, but the influence to survival length of flap has not been reported.
Summary of the invention
Present invention aims at the new application of exploitation asiaticosid, specially asiaticosid is promoting the random skin of ischemic overlength
The effect of valve survival.
Asiaticosid promote ischemic ultra long random flap survival during using the stomach-filling of oral cavity by the way of, by it is every 1 in the least
Gram asiaticosid powder is dissolved in 1 milliliter of physiological saline, is made into 1mg/ml solution, and application method is that every kg body weight rat is daily
Pass through oral cavity stomach-filling 40mg asiaticosid, 7 days as one therapeutic course.
It is drawn a conclusion by a large amount of zoopery, the survival surface for using asiaticosid that can make flap than obviously mentions
Height can promote ischemic ultra long random flap to survive well.The present invention is made into one below in conjunction with specific embodiments and drawings
Step is described in detail.
Detailed description of the invention
The comparison of Fig. 1 asiaticosid experimental group and the postoperative 7 days rat backs survival length of flap situation of saline control group
Figure；
Fig. 2 asiaticosid experimental group and saline control group two groups of flap blood perfusion amount paired observations in postoperative seven days；
Fig. 3 asiaticosid experimental group and saline control group flap lead oxide image contrast observe；
(100 times and 200 times) asiaticosid group and physiological saline group intermediate region flap HE dyeing observation feelings under Fig. 4 microscope
Condition；
Fig. 5 asiaticosid experimental group and physiological saline group vessel of flap endothelial growth factors (VEGF), interleukin-1 ' beta '
The protein expressions such as (IL-1 β), interleukin-6 (IL-6) and reversing tumor necrosis factor-alpha (TNF-α) (immunohistochemistry ×
400).
Specific embodiment
Asiaticosid can promote ischemic ultra long random flap viability to significantly improve.Promoting ischemic ultra long random flap
During survival by the way of the stomach-filling of oral cavity.It is dissolved in 1 milliliter of physiological saline by every 1 milligram of asiaticosid powder, is made into
1mg/ml solution, application method are that every kg body weight rat passes through oral cavity stomach-filling 40mg asiaticosid, 7 days as one therapeutic course daily.
The following are asiaticosids in the evaluation of effect for promoting the survival of ischemic Survival of Random Flap:
1, ischemic Survival of Random Flap model foundation
Male SD rat 36 for selecting health, are provided, cleaning grade, the Zhejiang SCXK(by Wenzhou Medical University's Experimental Animal Center)
2015-0019, weight 200-250g, 2-3 monthly ages.By rat according to random digits table be divided into asiaticosid experimental group and
Saline control group, every group 18.Using the McFarlane flap production method of improvement, the intraperitoneal injection of 1% yellow Jackets
Anesthesia, animal prone position is fixed, and is lost hair or feathers, iodophor disinfection, drape, using two interiliac line of rat tails as the base of a fruit, is hit exactly at back
A width 3cm, long 9cm rectangle random pattern skin flap are designed, design lines cut skin, and subcutaneous tissue reaches deep fascia shallow-layer, retain corium
Lower capillary network separates subcutaneous tissue in deep fascia shallow-layer surface, encounters well-known blood vessel i.e. with the ligation of 4-0 silk thread.Flap
After starting completely, thoroughly stops blooding, admire silk suture interrupted suture with 4-0 is medical immediately.It is mould that gold is smeared around notch after iodophor disinfection
Plain ointment, intraperitoneal injection of saline (50 ml/kg) Hemorrhagic shock.
Asiaticosid experimental group: 40 mg/kg asiaticosid stomach-fillings；Saline control group: same dose stomach-filling, often
Day 1 time, continuous injection 7 days, and solely cage is fed.To reduce surgical procedure bring error, all operations are completed by 1 people.
2, observation index:
The detection of 2.1 Flap survival ratios
The detection of Flap survival ratio: postoperative 7th day, each group rat accurately measured under narcosis with cellophane paper flap at
Living and necrosis area, and be cut into and survive or dead two parts, respectively with electronic scale weighing.Survival length of flap face is calculated as follows
Product ratio: Flap survival ratio=Flap survival glass paper weight/flap total surface area glass paper weight × 100%.Flap
Downright bad standard: flap is black, and tissue recoil, poor flexibility, quality is hard, cuts tissue not bleeding.Pathological manifestations are tissue
Disintegration, hypochromatosis, inflammatory cell infiltrate extensively, have focal bleeding.
Postoperative 7 days, asiaticosid group intermediate region flap color was light red, and surface is without scab hull shape at elasticity is preferable, distal area
Domain is black, shows there is scab shell, poor flexibility, sees that flap bleeding is active when starting flap in situ, amount of bleeding is more, without product under sarcolemma
Blood, hydrops, rich blood vessel.Physiological saline group flap intermediate region and remote area color black, and surface has scab hull shape at bullet
Property it is very poor, starting flap in situ sees that flap bleeding is less, and rheuminess object is more under sarcolemma, blood vessel relatively dredge (referring to Fig. 1).
The survival surface ratio of experimental group flap is (76.60 ± 3.48%) after 7 days, and control group Skin Flaps area ratio is
(49.54 ± 2.67%), compare the survival surface ratio of two groups of flaps, and difference is statistically significant (P < 0.01).
2.2 laser Doppler flowmetries measure new vessels
The 7th day after surgery, by two groups totally 12 SD rat anesthesias it is spare.Rat takes prostrate, and head and four limbs are bundled with nylon wire
Be fixed on station, with laser Doppler flowmetry measurement each region of skin flap of rats (flap proximal end (Ith area), middle-end (IIth area),
Distally (IIIth area)) blood perfusion blood flow.Groundwater increment (PU) indicates that the microcirculatory blood flow measured in local tissue depth is big
Small relative unit, i.e., the shift value that the flowing of red blood cell generates under Doppler, it is micro- that tissue has directly been reacted in the variation of PU value
The change of blood flow reflects that flap new vessels are formed indirectly.Data give special-purpose software moorLDI review V6.1 into
Row analysis, statistics.
Laser Doppler flowmetry shows that the intermediate ends blood flow of asiaticosid group flap is significantly more than control group after 7 days,
The blood perfusion amount of asiaticosid group flap be (236.24 ± 42.00), control group flap blood perfusion amount be (48.45 ±
14.90), compare the blood perfusion amount of two groups of flaps, difference statistically significant (P < 0.01) (referring to fig. 2).
2.3 gelatin-lead oxide angiography
It postoperative 7th day, is first passed through after anesthesia to one bilateral common carotid artery of rat and injects 0.9% physiological saline, ipsilateral jugular vein bloodletting empties
Preset gelatin+lead oxide perfusion liquid (100ML/kg) is then slowly injected into arteria carotis by blood in rat body, when observing
Scleral and limb end color stop injection after becoming contrast agent color.Rat is refrigerated 12-24 hours after being perfused successfully,
It is aggregated gelatin, finally dissects rat back flap and surrounding skin, tile row X-ray photographic.
Asiaticosid group flap distal end contrast agent is full, and the contrast agent of control group is confined to flap proximal end and intermediate region
(referring to Fig. 3).
2.4 histology
It postoperative 7 days, is sampled in flap midpoint.Sample is fixed through 10% formaldehyde, paraffin embedding, HE dyeing, postoperative 7d light microscopic
Under (× 100 and × 200) observe granulation tissue thickness degree, the structure change of capillary, tissue edema, necrosis, inflammatory cell
Situations such as infiltration.
Asiaticosid group is shown in fibroblast proliferation, and granulation tissue is relatively thin, and tissue edema is less, and inflammatory cell infiltration is few.
Physiological saline group fibroblast proliferation is less, and tissue edema is obvious, and inflammatory cell infiltration is serious (referring to fig. 4).
Asiaticosid group area's microvessel density in flap is (34.16 ± 2.77), control group area's capilary in flap
Density is (14.72 ± 2.14), and area's microvessel density compares in two groups of flaps, and difference is statistically significant (P < 0.01).
Asiaticosid group in flap area's neutrophil leucocyte density be (23.97 ± 6.24) it is a/mm2Compare saline control
Group neutrophil leucocyte density (37.45 ± 3.39) it is a/mm2Be substantially reduced, two groups of comparing differences it is statistically significant (P <
0.01).
2.5 immunohistochemical observation
It is situated between using based on Streptavidin/peroxidase experimental principle to vascular endothelial growth factor (VEGF), leucocyte
The protein expression levels such as -1 β of element (IL-1 β), interleukin-6 (IL-6) and reversing tumor necrosis factor-alpha (TNF-α) carry out
Immunohistochemical evaluation.Immuning tissue is sliced using 6.0 Color Image Analysis network analysis each group of Image-Pro Plus
It learns coloration result (referring to Fig. 5).
Immunohistochemical staining discovery asiaticosid group skin flap of rats vegf expression is apparently higher than control group.Asiaticosid group
Vegf expression is (4245.83 ± 182.64) IA, and the vegf expression of control group is (1941.00 ± 173.52 IA), two groups
Vegf expression compares, and difference is statistically significant (P < 0.01).Asiaticosid group IL-1 β expression (1361.00 ±
256.39), IL-6 expresses (2102.50 ± 185.79) and TNF-α expression (1859.33 ± 156.57) significantly lower than life
Manage saline control group IL-1 β expression (2467.33 ± 342.43), IL-6 expression (5637.83 ± 267.56) and TNF-α
It expresses (2951.67 ± 254.84), two groups of expressions, difference is statistically significant (P < 0.01).
The detection that 2.6 superoxide dismutases (SOD), malonaldehyde (MDA) are expressed
Postoperative 7 days, area, position, center cut the cm holostrome tissue of 0.5 cm × 0.5 in flap, removes sarcolemma layer, claims quality,
Dilution, ice water homogenate is according to SOD, MDA detection kit specification, both detections content.
((58.57 ± 2.23) U is significantly higher than physiology salt to every milligram of Protein S OD activity expression amount of asiaticosid experimental group
Water control group (23.89 ± 2.51) U, every milligram of albumen MDA expression quantity (21.69 ± 3.00) of asiaticosid experimental group
Nmol is substantially less than physiological saline group ((56.74 ± 1.67) nmol (P < 0.01).Two groups of SOD values and MDA comparision contents,
Difference is statistically significant (P < 0.05).
Conclusion: asiaticosid can promote surviving for rat ischemia Survival of Random Flap, and mechanism is possible:
1, the expression of asiaticosid up-regulation vessel of flap endothelial growth factors (VEGF), stimulation flap distal vessels are newborn, improve
Flap of blood supplies, to improve the survival surface of flap；
2, asiaticosid can mitigate tissue inflammation reaction, reduce inflammatory factor interleukin-1 ' beta ' (IL-1 β), leucocyte is situated between
Element -6(IL-6) and the protein expressions such as reversing tumor necrosis factor-alpha (TNF-α), to promote survival length of flap；
3, asiaticosid can promote Survival of Random Flap with antagonism tissue lipid peroxidization, inhibition flap ischemia reperfusion injury
Survival.
Claims (2)
1. asiaticosid is in the effect for promoting the survival of ischemic ultra long random flap.
2. asiaticosid according to claim 1 is in the effect for promoting the survival of ischemic ultra long random flap, it is characterised in that:
It is dissolved in 1 milliliter of physiological saline by every 1 milligram of asiaticosid powder, is made into 1mg/ml solution, application method is every kg body weight
Rat passes through oral cavity stomach-filling 40mg asiaticosid, 7 days as one therapeutic course daily.
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| CN201910124342.7A CN109620835A (en) | 2019-02-19 | 2019-02-19 | Asiaticosid is in the effect for promoting the survival of ischemic ultra long random flap |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111973583A (en) * | 2020-07-29 | 2020-11-24 | 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 | Function of apigenin in preparation of medicine for promoting survival of ischemic overlong random skin flap |
Citations (4)
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| CN101822685A (en) * | 2009-03-06 | 2010-09-08 | 北京卓越同创药物研究院 | Application of asiaticoside |
| CN103330715A (en) * | 2013-07-01 | 2013-10-02 | 华仁药业股份有限公司 | Peritoneal dialysis solution for resisting fibration of peritonaeum |
| CN107007761A (en) * | 2017-06-05 | 2017-08-04 | 唐永奎 | A kind of Chinese medicine burn oil and preparation method thereof |
| CN108143844A (en) * | 2016-12-02 | 2018-06-12 | 白藜芦醇作者生技研发有限公司 | For maintaining the epidermal stem cells of skin and there is the Chinese herbal medicine composition and its facial mask of multiple functions |
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2019
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Patent Citations (4)
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| CN101822685A (en) * | 2009-03-06 | 2010-09-08 | 北京卓越同创药物研究院 | Application of asiaticoside |
| CN103330715A (en) * | 2013-07-01 | 2013-10-02 | 华仁药业股份有限公司 | Peritoneal dialysis solution for resisting fibration of peritonaeum |
| CN108143844A (en) * | 2016-12-02 | 2018-06-12 | 白藜芦醇作者生技研发有限公司 | For maintaining the epidermal stem cells of skin and there is the Chinese herbal medicine composition and its facial mask of multiple functions |
| CN107007761A (en) * | 2017-06-05 | 2017-08-04 | 唐永奎 | A kind of Chinese medicine burn oil and preparation method thereof |
Non-Patent Citations (4)
| Title |
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| XIGUANG FENG ET AL: "Effects of Asiaticoside Treatment on the Survival of Random Skin Flaps in Rats", 《JOURNAL OF INVESTIGATIVE SURGERY》 * |
| YOSHIYUKI KIMURA ET AL.: "Facilitating action of asiaticoside at low doses on burn wound repair and its mechanism", 《EUROPEAN JOURNAL OF PHARMACOLOGY》 * |
| 主编 钟剑平: "《中国外科年鉴（2008）》", 31 March 2009, 第二军医大学出版社 * |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111973583A (en) * | 2020-07-29 | 2020-11-24 | 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 | Function of apigenin in preparation of medicine for promoting survival of ischemic overlong random skin flap |
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Application publication date: 20190416 |