RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Flap necrosis is the most common complication after flap transplantation, but its prevention remains challenging. Tetrahydropalmatine (THP) is the main bioactive component of the traditional Chinese medicine Corydalis yanhusuo, with effects that include the activation of blood circulation, the promotion of qi, and pain relief. Although THP is widely used to treat various pain conditions, its impact on flap survival is unknown. AIM OF THE STUDY: To explore the effect and mechanism of THP on skin flap survival. MATERIALS AND METHODS: In this study, we established a modified McFarlane flap model, and the flap survival rate was calculated after 7 days of THP treatment. Angiogenesis and blood perfusion were evaluated using lead oxide/gelatin angiography and laser Doppler, respectively. Flap tissue obtained from zone II was evaluated histopathologically, by hematoxylin and eosin staining, and in assays for malondialdehyde content and superoxide dismutase activity. Immunofluorescence was performed to detect interleukin (IL)-6, tumor necrosis factor (TNF)-α, hypoxia-inducible factor (HIF)-1α, Bcl-2, Bax, caspase-3, caspase-9, SQSTM1/P62, Beclin-1, and LC3 expression, and Western blot to assess PI3K/AKT signaling pathway activation and Vascular endothelial growth factor (VEGF) expression. The role played by the autophagy pathway in flap necrosis was examined using rapamycin, a specific inhibitor of mTOR. RESULTS: Experimentally, THP improved the survival rate of skin flaps, promoted angiogenesis, and improved blood perfusion. THP administration reduced the inflammatory response, oxidative stress, and apoptosis in addition to inhibiting autophagy via the PI3K/AKT/mTOR pathway. Rapamycin partially reversed these effects. CONCLUSION: THP promotes skin flap survival via the PI3K/AKT signaling pathway.
Asunto(s)
Alcaloides de Berberina , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Necrosis , Sirolimus/farmacología , DolorRESUMEN
Flaps are mainly used for wound repair. However, postoperative ischemic necrosis of the distal flap is a major problem, which needs to be addressed urgently. We evaluated whether tetrandrine, a compound found in traditional Chinese medicine, can prolong the survival rate of random skin flaps. Thirty-six rats were randomly divided into control, low-dose tetrandrine (25 mg/kg/day), and high-dose tetrandrine (60 mg/kg/day) groups. On postoperative Day 7, the flap survival and average survival area were determined. After the rats were sacrificed, the levels of angiogenesis, apoptosis, and inflammation in the flap tissue were detected with immunology and molecular biology analyses. Tetrandrine increased vascular endothelial growth factor and Bcl-2 expression, in turn promoting angiogenesis and anti-apoptotic processes, respectively. Additionally, tetrandrine decreased the expression of Bax, which is associated with the induction of apoptosis, and also decreased inflammation in the flap tissue. Tetrandrine improved the survival rate of random flaps by promoting angiogenesis, inhibiting apoptosis, and reducing inflammation in the flap tissue through the modulation of the PI3K/AKT signaling pathway.
Asunto(s)
Bencilisoquinolinas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Ratas , Animales , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular , Transducción de Señal , Inflamación , PielRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The clinical application of skin flaps in surgical reconstruction is frequently impeded by the occurrence of distant necrosis. L-Borneol exhibits myogenic properties in traditional Chinese medicine and is used in clinical settings to promote wound healing and conditions such as stroke. Nevertheless, the precise mechanism by which borneol exerts its protective effects on skin flap survival remains unclear. AIM OF THE STUDY: To explore the potential of L-borneol to promote skin flap survival and elucidate the underlying mechanisms. MATERIALS AND METHODS: Thirty-six male Sprague-Dawley rats were randomly divided into three groups: a high-dose (200 mg/kg L-borneol per day), a low-dose (50 mg/kg/day), and control group (same volume of solvent). In each rat, a modified rectangular McFarlane flap model measuring 3 × 9 cm was constructed. Daily intragastric administration of L-borneol or solvent was performed. The flap was divided into three square sections of equal size, namely Zone I (the proximal zone), Zone II (the intermediate zone), and Zone III (the distal zone). The survival rate was quantified, and the histological state of each flap was evaluated on the seventh day following the surgical procedure. The assessment of angiogenesis was conducted using lead oxide/gelatin angiography, whereas the evaluation of blood flow in the free flap was performed using laser Doppler flow imaging. Superoxide dismutase activity was detected using the water-soluble tetrazolium salt-8 method. The quantities of vascular endothelial growth factor, interleukin (IL)-1ß, IL-6, and tumour necrosis factor-α were determined using immunohistochemistry. The levels of nuclear transcription factor-κB, hypoxia-inducible factor-1, B-cell lymphoma-2 (BCL-2), and BCL-2-associated X (BAX) were determined by Western blotting technique. RESULTS: Flap survival rate significantly improved and neutrophil recruitment and release were enhanced after treatment with the compound. Angiogenesis was promoted. L-borneol protected against oxidative stress by increasing superoxide dismutase activity and decreasing malondialdehyde content. It downregulated the hypoxia-inducible factor nuclear transcription factor-κB pathway, leading to the inhibition of several inflammatory factors. Simultaneously, it facilitated the expression of vascular endothelial growth factor and BCL-2. CONCLUSION: The study shows that L-borneol may promote skin flap survival by inhibiting HIF-1α/NF-κB pathway.
Asunto(s)
FN-kappa B , Factor A de Crecimiento Endotelial Vascular , Ratas , Masculino , Animales , Ratas Sprague-Dawley , FN-kappa B/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Superóxido Dismutasa/metabolismo , Solventes , Hipoxia/metabolismo , Piel/metabolismoRESUMEN
BACKGROUND: Flaps are commonly used for repairing tissues and wounds in surgery. However, various factors can cause postoperative necrosis in these flaps. Catalpol is a bioactive component in extracts from Rehmannia glutinosa , which has pharmacologic characteristics that may improve flap survival. METHODS: The experiments were performed in 36 male Sprague-Dawley rats divided into three groups: control, low-dose catalpol, and high-dose catalpol. The flap survival rate, neutrophil density, microvessel density, superoxide dismutase, and malondialdehyde levels were measured; histopathologic analysis was performed 7 days after surgery. Blood flow was measured by laser Doppler flowmetry and lead oxide-gelatin angiography. The levels of vascular endothelial growth factor, toll-like receptor 4, nuclear factor-kappa B, tumor necrosis factor-α, interleukin (IL)-6, nod-like receptor 3, cysteinyl aspartate specific proteinase-1 (caspase-1), IL-1ß, and IL-18 were determined by immunohistochemistry. RESULTS: Catalpol treatment increased flap survival, reduced neutrophil recruitment and release, decreased malondialdehyde levels, and increased superoxide dismutase levels; thus, it effectively reduced oxidative stress, up-regulated the expression of vascular endothelial growth factor, and increased microvessel density. Laser Doppler flowmetry and lead oxide-gelatin angiography showed that catalpol treatment improved angiogenesis. Immunohistochemical analyses showed that catalpol inhibited the production of inflammatory factors, such as tumor necrosis factor-α and IL-6, by down-regulating toll-like receptor 4 and nuclear factor-κB. Furthermore, catalpol reduced cell pyroptosis by inhibiting the production of nod-like receptor 3 inflammasomes, thereby down-regulating the release of IL-1ß and IL-18. CONCLUSION: Catalpol can improve the rate of flap survival. CLINICAL RELEVANCE STATEMENT: The research verified that the Rehmannia extract catalpol, through angiogenesis, inflammatory response, ischemia-reperfusion injury, and pyroptosis-related pathways, effectively improved the flap survival rate, which will provide new ideas for clinical medication.
Asunto(s)
Glucósidos Iridoides , Plomo , Óxidos , Rehmannia , Masculino , Ratas , Animales , Rehmannia/metabolismo , Interleucina-18 , Receptor Toll-Like 4 , Factor de Necrosis Tumoral alfa , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular , Gelatina , FN-kappa B/metabolismo , Interleucina-6 , Malondialdehído , Proteínas NLR , Superóxido DismutasaRESUMEN
Objective: Random skin flaps have many applications in plastic and reconstructive surgeries. However, distal flap necrosis restricts wider clinical utility. Mitophagy, a vital form of autophagy for damaged mitochondria, is excessively activated in flap ischemia/reperfusion (I/R) injury, thus inducing cell death. Aldehyde dehydrogenase-2 (ALDH2), an allosteric tetrameric enzyme, plays an important role in regulating mitophagy. We explored whether ALDH2 activated by N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide (Alda-1) could reduce the risk of ischemic random skin flap necrosis, and the possible mechanism of action. Methods: Modified McFarlane flap models were established in 36 male Sprague-Dawley rats assigned randomly to three groups: a low-dose Alda-1 group (10 mg/kg/day), a high-dose Alda-1 group (20 mg/kg/day) and a control group. The percentage surviving skin flap area, neutrophil density and microvessel density (MVD) were evaluated on day 7. Oxidative stress was quantitated by measuring the superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Blood perfusion and skin flap angiogenesis were assessed via laser Doppler flow imaging and lead oxide-gelatin angiography, respectively. The expression levels of inflammatory cytokines (IL-1ß, IL-6, and TNF-α), vascular endothelial growth factor (VEGF), ALDH2, PTEN-induced kinase 1 (PINK1), and E3 ubiquitin ligase (Parkin) were immunohistochemically detected. Indicators of mitophagy such as Beclin-1, p62, and microtubule-associated protein light chain 3 (LC3) were evaluated by immunofluorescence. Results: Alda-1 significantly enhanced the survival area of random skin flaps. The SOD activity increased and the MDA level decreased, suggesting that Alda-1 reduced oxidative stress. ALDH2 was upregulated, and mitophagy-related proteins (PINK1, Parkin, Beclin-1, p62, and LC3) were downregulated, indicating that ALDH2 inhibited mitophagy through the PINK1/Parkin signaling pathway. Treatment with Alda-1 reduced neutrophil infiltration and expressions of inflammatory cytokines. Alda-1 significantly upregulated VEGF expression, increased the MVD, promoted angiogenesis, and enhanced blood perfusion. Conclusion: ALDH2 activation can effectively enhance random skin flap viability via inhibiting PINK1/Parkin-dependent mitophagy. Moreover, enhancement of ALDH2 activity also exerts anti-inflammatory and angiogenic properties.
Asunto(s)
Daño por Reperfusión , Factor A de Crecimiento Endotelial Vascular , Animales , Masculino , Ratas , Aldehído Deshidrogenasa/uso terapéutico , Beclina-1 , Citocinas/uso terapéutico , Isquemia , Necrosis , Complicaciones Posoperatorias , Proteínas Quinasas/metabolismo , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Superóxido Dismutasa , Ubiquitina-Proteína Ligasas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Random skin flaps have limited clinical application as a broad surgical reconstruction treatment because of distal necrosis. The prolyl hydroxylase domain-containing protein inhibitor roxadustat (RXD) enhances angiogenesis and reduces oxidative stress and inflammation. This study explored the function of RXD in the survival of random skin flaps. Thirty-six male Sprague-Dawley rats were randomly divided into low-dose RXD group (L-RXD group, 10 mg/kg/2 day), high-dose RXD group (H-RXD group, 25 mg/kg/2 day), and control group (1 mL of solvent, 1:9 DMSO:corn oil). The proportion of surviving flaps was determined on day 7 after surgery. Angiogenesis was assessed by lead oxide/gelatin angiography, and microcirculation blood perfusion was evaluated by laser Doppler flow imaging. Specimens in zone II were obtained, and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured as indicators of oxidative stress. Histopathological status was evaluated with haematoxylin and eosin staining. The levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and the inflammatory factors interleukin (IL)-1ß, IL-6, and tumour necrosis factor-α (TNF-α) were detected by immunohistochemistry. RXD promoted flap survival and microcirculatory blood perfusion. Angiogenesis was detected distinctly in the experimental group. SOD activity increased and the MDA level decreased in the experimental group. Immunohistochemistry indicated that the expression levels of HIF-1α and VEGF were increased while the levels of IL-6, IL-1ß, and TNF-α were decreased after RXD injection. RXD promoted random flap survival by reinforcing vascular hyperplasia and decreasing inflammation and ischaemia-reperfusion injury.
Asunto(s)
Factor de Necrosis Tumoral alfa , Factor A de Crecimiento Endotelial Vascular , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/metabolismo , Interleucina-6 , Subunidad alfa del Factor 1 Inducible por Hipoxia , Microcirculación , Superóxido Dismutasa/metabolismo , InflamaciónRESUMEN
Random skin flaps are often used in reconstruction operations. However, flap necrosis is still a common postoperative complication. Here, we investigated whether berberine (C20 H19 NO5 , BBR), a drug with antioxidant activity, improves the survival rate of random flaps. Fifty-four rats were divided into three groups: control, BBR and BBR + L -NAME groups (L -NAME, L -NG -Nitro-arginine methyl ester). The survival condition and the percentage of survival area of the flaps were evaluated on the seventh day after surgery. After animals were sacrificed, angiogenesis, apoptosis, oxidative stress and inflammation levels were assessed by histological and protein analyses. Our findings suggest that berberine promotes flap survival. The level of angiogenesis increased; the levels of oxidative stress, inflammation and apoptosis decreased; the levels of phosphoinositide 3-kinase (PI3K), phospho-Akt (p-Akt) and phospho-endothelial nitric oxide synthase (p-eNOS) increased in the flap tissue; and L -NAME reversed the effects of berberine on random skin flaps. Statistical analysis showed that the BBR group results differed significantly from those of the control and the BBR + L -NAME groups (p < .05). Our results confirm that berberine is an effective drug for significantly improving the survival rate of random skin flaps by promoting angiogenesis, inhibiting inflammation, attenuating oxidative stress, and reducing apoptosis through the PI3K/Akt/eNOS signaling pathway.
Asunto(s)
Berberina , Fosfatidilinositol 3-Quinasas , Ratas , Animales , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Berberina/farmacología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Transducción de Señal , NG-Nitroarginina Metil Éster/farmacologíaRESUMEN
Background: Asiaticoside (AS) is extracted from the traditional herbal medicine Centella asiatica, and has angiogenic, antioxidant, anti-inflammatory, and wound-healing effects. We investigated the effects of AS on skin flap survival. Methods: Dorsal McFarlane flaps were harvested from 36 rats and divided into two groups: an experimental group treated with 40 mg/kg AS administered orally once daily, and a control group administered normal saline in an identical manner. On day 2, superoxide dismutase (SOD) and malondialdehyde (MDA) levels, and production of the cytokines tumor necrosis factor-α and interleukin (IL)-6 were evaluated. On day 7, tissue slices were stained with hematoxylin and eosin. The expression of vascular endothelial growth factor (VEGF), IL-6, and IL-1ß were immunohistochemically evaluated. Microcirculatory flow was measured using laser Doppler flowmetry. Flap angiography, using the lead oxide-gelatin injection technique, was performed with the aid of a soft X-ray machine. Results: The AS group exhibited greater mean flap survival area, improved microcirculatory flow, and higher expression levels of SOD and VEGF compared with the control group. However, MDA levels and the inflammatory response were significantly reduced. Conclusions: AS exhibits promise as a therapeutic option due to its effects on the viability and function of random skin flaps in rats.
Asunto(s)
Neovascularización Fisiológica , Colgajos Quirúrgicos , Triterpenos , Factor A de Crecimiento Endotelial Vascular , Animales , Supervivencia de Injerto , Microcirculación , Ratas , Ratas Sprague-Dawley , Piel , Triterpenos/farmacologíaRESUMEN
Random skin flaps are widely used to repair tissue defects. However, the distal flap regions are prone to ischemic necrosis, limiting clinical applications. Azadirachtin A, a fruit extract from the neem, improves tissue blood supply and metabolism, reduces cell swelling, promotes tissue healing, and prevents venous thrombosis. We explored whether it enhances random skin flap survival. Fifty-four Sprague-Dawley rats were divided into control, low-dose, and high-dose Azadirachtin A-treated groups using a random number table. We used an improved version of the McFarlane technique to create flaps. On day 2, superoxide dismutase and malondialdehyde levels were measured. Tissue slices prepared on day 7 were stained with hematoxylin and eosin. The expression levels of vascular endothelial growth factor (VEGF), toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-kB), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were immunohistochemically assayed. Microcirculatory blood flow was measured via laser Doppler blood flowmetry. Flap angiography was performed using the lead-oxide gelatin injection technique. And the azadirachtin A groups exhibited a greater mean flap survival area, an improved mean blood vessel density, a greater blood flow, and higher superoxide dismutase and VEGF levels, especially at the high dose. Azadirachtin A markedly reduced the levels of TNF-α, IL-6, IL-1ß, TLR4, and NF-kB. These findings suggest that azadirachtin A promotes random skin flap survival by improving the blood supply, reducing tissue inflammation, and inhibiting flap ischemia reperfusion injury.
Asunto(s)
Antiinflamatorios/farmacología , Limoninas/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Colgajos Quirúrgicos/irrigación sanguínea , Angiografía , Animales , Regulación hacia Abajo/efectos de los fármacos , Gelatina/química , Interleucina-6/metabolismo , Plomo/química , Limoninas/química , Masculino , Malondialdehído/metabolismo , Microvasos/efectos de los fármacos , Microvasos/patología , Neutrófilos/efectos de los fármacos , Óxidos/química , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Objective: To determine the effect of Shu Xue Tong treatment on random skin flap survival. Methods: Twenty-four male Sprague-Dawley (SD) rats were administered Shu Xue Tong or normal saline. On postoperative day 7, flap survival area, flap angiogenesis angiography, blood flow and vascular endothelial growth factor (VEGF), Notch1, and Delta-like ligand 4 (Dll4) expression were assessed. Results: The mean flap survival area, blood vessel regeneration, microcirculatory flow, and expression of VEGF were enhanced with Shu Xue Tong treatment relative to the control. However, in Shu Xue Tong-treated rat flap, Notch1 and Dll4 levels were significantly reduced. Conclusions: These results demonstrate the beneficial action of Shu Xue Tong on random skin flap survival and suggest that its mechanism of action involves the promotion of angiogenesis via the VEGF-Notch1/Dll4 signaling pathway.
Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Supervivencia de Injerto/efectos de los fármacos , Colgajos Quirúrgicos/trasplante , Angiografía , Animales , Evaluación Preclínica de Medicamentos , Inyecciones Intravenosas , Péptidos y Proteínas de Señalización Intracelular/análisis , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Proteínas de la Membrana/análisis , Proteínas de la Membrana/metabolismo , Microcirculación/efectos de los fármacos , Modelos Animales , Neovascularización Fisiológica/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptor Notch1/análisis , Receptor Notch1/metabolismo , Transducción de Señal/efectos de los fármacos , Piel/irrigación sanguínea , Piel/efectos de los fármacos , Colgajos Quirúrgicos/irrigación sanguínea , Factor A de Crecimiento Endotelial Vascular/análisis , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
With the advantage of handy process, random pattern skin flaps are generally applied in limb reconstruction and wound repair. Apelin-13 is a discovered endogenous peptide, that has been shown to have potent multiple biological functions. Recently, thermosensitive gel-forming systems have gained increasing attention as wound dressings due to their advantages. In the present study, an apelin-13-loaded chitosan (CH)/ß-sodium glycerophosphate (ß-GP) hydrogel was developed for promoting random skin flap survival. Random skin flaps were created in 60 rats after which the animals were categorized to a control hydrogel group and an apelin-13 hydrogel group. The water content of the flap as well as the survival area were then measured 7 days post-surgery. Hematoxylin and eosin staining was used to evaluate the flap angiogenesis. Cell differentiation 34 (CD34) and vascular endothelial growth factor (VEGF) levels were detected by immunohistochemistry and Western blotting. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were assessed by enzyme linked immunosorbent assays (ELISAs). Oxidative stress was estimated via the activity of tissue malondialdehyde (MDA) and superoxide dismutase (SOD). Our results showed that CH/ß-GP/apelin-13 hydrogel could not only reduce the tissue edema, but also improve the survival area of flap. CH/ß-GP/apelin-13 hydrogel also upregulated levels of VEGF protein and increased mean vessel densities. Furthermore, CH/ß-GP/apelin-13 hydrogel was shown to significantly inhibit the expression of TNF-α and IL-6, along with increasing the activity of SOD and suppressing the MDA content. Taken together, these results indicate that this CH/ß-GP/apelin-13 hydrogel may be a potential therapeutic way for random pattern skin flap.
Asunto(s)
Supervivencia de Injerto/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/administración & dosificación , Péptidos y Proteínas de Señalización Intercelular/farmacocinética , Trasplante de Piel/métodos , Piel/efectos de los fármacos , Temperatura , Animales , Temperatura Corporal/fisiología , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/farmacocinética , Evaluación Preclínica de Medicamentos , Hidrogeles/administración & dosificación , Hidrogeles/farmacocinética , Masculino , Malondialdehído/metabolismo , Necrosis/patología , Necrosis/prevención & control , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Piel/metabolismo , Piel/patología , Fenómenos Fisiológicos de la Piel/efectos de los fármacos , Colgajos Quirúrgicos/fisiología , Colgajos Quirúrgicos/trasplanteRESUMEN
This study was performed to examine the protective effects of icariin (ICA) on ischemic random skin flaps. A rat random-pattern skin flap model was established, and animals in the low-dose and high-dose experimental groups were administered ICA intraperitoneally at doses of 40 and 80â¯mg/kg, respectively, once daily for 7 days after the initial surgery. Control rats received vehicle according to the same schedule. Survival rates were observed and recorded using transparent graph paper, and flaps were obtained and stained with hematoxylin and eosin (H&E). The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the flap tissue were assessed. The blood flow volume was determined by the laser Doppler method, and tissue expression levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), interleukin-1ß, and phosphodiesterase 5 (PDE5) were scored immunohistochemically. The levels of proinflammatory cytokines, including tumor necrosis factor-α and IL-6, were determined by enzyme-linked immunosorbent assay. The main flap survival area was significantly larger in rats treated with ICA than in vehicle-treated controls. H&E staining showed an inhibitory effect of ICA on inflammation, especially at the high dose. In addition, ICA treatment was associated with decreases in the tissue MDA level, proinflammatory cytokine production, and the level of PDE5, but increases in SOD activity, blood flow volume, and the level of VEGF expression. The findings of the present study suggest that ICA is a potential therapeutic agent for random-pattern skin flap necrosis in the clinical setting.
Asunto(s)
Flavonoides/farmacología , Piel/patología , Colgajos Quirúrgicos , Supervivencia Tisular/efectos de los fármacos , Animales , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Isquemia/metabolismo , Isquemia/patología , Isquemia/fisiopatología , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/efectos de los fármacos , Piel/irrigación sanguínea , Superóxido Dismutasa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Random skin flaps are routinely placed during plastic and reconstructive surgery, but the distal areas often develop ischemia and necrosis. Baicalein, a major flavonoid extracted from the traditional Chinese herbal medicine huangqin, Scutellaria baicalensis Georgi, may improve flap viability. MATERIALS AND METHODS: Rats were randomly divided into baicalein and control groups and they underwent placement of modified McFarlane flaps after intraperitoneal administration of baicalein or vehicle. Flap survival and water content were measured 7 days later, as were angiogenesis, apoptosis, and oxidative stress in ischemic flaps. RESULTS: Baicalein promoted flap survival, reduced edema, increased mean vessel density, and enhanced vascular endothelial growth factor production at both the translational and transcriptional levels. Baicalein reduced caspase 3 cleavage, increased superoxidase dismutase and glutathione levels, and decreased the malondialdehyde level. CONCLUSION: Baicalein promoted flap viability by stimulating angiogenesis and inhibiting apoptosis and oxidation.
Asunto(s)
Edema/tratamiento farmacológico , Flavanonas/farmacología , Medicina Tradicional China , Piel/efectos de los fármacos , Colgajos Quirúrgicos , Animales , Apoptosis/efectos de los fármacos , Edema/metabolismo , Edema/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Dilong injection as a medicinal preparation extracted from earthworm in traditional Chinese medicine, is used to activate blood circulation and remove blood stasis. In this research, we aim to investigate its potential effect on random skin flap survival in rat models. MATERIALS AND METHODS: McFarlane flaps were established in 60 male Sprague-Dawley rats randomly divided into two groups: the control group and the Dilong injection group. Diong injection group was injected with the Diong injection (4 mL/kg) once a day for seven days, and the control group was given an equal volume of saline solution. After seven days, flaps were obtained and stained with Hematoxylin and Eosin. Histological examination was done to determine changes in histology such as thickness of granulation tissue, tissue edema, neutrophil infiltration, and the microvascular density (MVD). In addition, immunohistochemical detection was carried out to show vascular endothelial growth factor (VEGF) expression level. RESULTS: Compared with the control group, the Dilong group exhibited more fibroblastic proliferation, thinner neutrophil infiltration with less edema through histological examination. The MVD and the VEGF expression of flaps were significantly higher. The mean superoxide dismutase activity was evidently higher in the Dilong group than in the control group, while the mean MDA level was lower. CONCLUSIONS: According to the comparison made between the two groups for histological and immunohistochemical evaluation, the Dilong injection group has potential effects on the survival of random skin flaps in rat models.
Asunto(s)
Supervivencia de Injerto/efectos de los fármacos , Medicina Tradicional China/métodos , Oligoquetos/química , Procedimientos de Cirugía Plástica/efectos adversos , Colgajos Quirúrgicos/efectos adversos , Extractos de Tejidos/farmacología , Animales , Inyecciones Subcutáneas , Masculino , Malondialdehído/metabolismo , Microvasos/efectos de los fármacos , Modelos Animales , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Procedimientos de Cirugía Plástica/métodos , Superóxido Dismutasa/metabolismo , Colgajos Quirúrgicos/irrigación sanguínea , Colgajos Quirúrgicos/patología , Extractos de Tejidos/química , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Random skin flaps are commonly used for wound repair and reconstruction. Electroacupuncture at The Zusanli point could enhance microcirculation and blood perfusion in random skin flaps. OBJECTIVE: To determine whether electroacupuncture at The Zusanli point can improve the survival of random skin flaps in a rat model. MATERIALS AND METHODS: Thirty-six male Sprague Dawley rats were randomly divided into 3 groups: control group (no electroacupuncture), Group A (electroacupuncture at a nonacupoint near The Zusanli point), and Group B (electroacupuncture at The Zusanli point). McFarlane flaps were established. On postoperative Day 2, malondialdehyde (MDA) and superoxide dismutase were detected. The flap survival rate was evaluated, inflammation was examined in hematoxylin and eosin-stained slices, and the expression of vascular endothelial growth factor (VEGF) was measured immunohistochemically on Day 7. RESULTS: The mean survival area of the flaps in Group B was significantly larger than that in the control group and Group A. Superoxide dismutase activity and VEGF expression level were significantly higher in Group B than those in the control group and Group A, whereas MDA and inflammation levels in Group B were significantly lower than those in the other 2 groups. CONCLUSION: Electroacupuncture at The Zusanli point can effectively improve the random flap survival.
Asunto(s)
Electroacupuntura , Supervivencia de Injerto , Colgajos Quirúrgicos/irrigación sanguínea , Colgajos Quirúrgicos/fisiología , Abdomen , Animales , Electroacupuntura/métodos , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Trasplante de PielRESUMEN
BACKGROUND: Huangqi (Radix astragali) is a traditional Chinese drug, designed to "buqi," which means invigorating vital energy, widely used in clinical settings. We investigated the effect of Huangqi injection on the survival of random skin flaps. METHODS: McFarlane flaps were established in 60 rats divided into two groups. Postoperative celiac injections were given to both groups for 7 days. Huangqi was injected into the test group, and saline was injected into controls. On day 7, tissues were stained with hematoxylin and eosin, immunohistochemically evaluated, and the expression levels of xanthine oxidase determined. RESULT: The mean area of flap survival in the test group was significantly higher compared with the controls. Expression of vascular endothelial growth factor and superoxide dismutase, and microvessel development, were markedly increased in the test group, and the malondialdehyde level was reduced. CONCLUSION: Huangqi injection promotes random skin flap survival.
Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Supervivencia de Injerto/efectos de los fármacos , Colgajos Quirúrgicos/patología , Animales , Astragalus propinquus , Modelos Animales de Enfermedad , Rechazo de Injerto/prevención & control , Inmunohistoquímica , Inyecciones Intradérmicas , Masculino , Malondialdehído/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Medición de Riesgo , Trasplante de Piel/efectos adversos , Trasplante de Piel/métodos , Superóxido Dismutasa/metabolismo , Colgajos Quirúrgicos/efectos adversos , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiologíaRESUMEN
BACKGROUND: A Shuxuetong injection is traditionally used in Chinese medicine to treat "blood stasis and stagnation" (yu xue yu zhi). We investigated the effect of such injection on the survival of random skin flaps. METHODS: McFarlane flaps were established in 60 rats divided into two groups. Postoperative celiac injections were given to both groups for 7 days. Shuxuetong was injected into the test group, and saline was injected into controls. On day 7, tissues were stained with H&E (hematoxylin-eosin) stain, immunohistochemically evaluated, and the expression levels of xanthine oxidase were determined. RESULT: The mean area of flap survival in the test group was significantly higher than in controls. Expression of vascular endothelial growth factor and superoxide dismutase, and microvessel development, were markedly increased in the test group, and the malondialdehyde level was reduced. CONCLUSION: Shuxuetong promotes random skin flap survival.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Colgajos Quirúrgicos , Animales , Medicamentos Herbarios Chinos/administración & dosificación , Supervivencia de Injerto/efectos de los fármacos , Inmunohistoquímica , Inyecciones , Masculino , Medicina Tradicional China , Modelos Animales , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Xantina Oxidasa/metabolismoRESUMEN
OBJECTIVE: To observe the effects of Ixeri sonhifolia injection on random skin flap survival in rats. METHODS: Dorsal full-thickness skin flap model were harvested from 24 Sprague-Dawley rats in 2 to 3 months old. Twelve rats in experimental group were injected intraperitoneally with 5 ml/kg Ixeri sonhifolia injection immediately after the operation, the other rats in control group with an equal volume of saline. The rats were killed by cervical dislocation after 7 days' Ixeri sonhifolia injection. The area ratio of the survival tissue was measured at the 7th day,the tissue samples from proximal, middle, and distal portions were stained by HE and sectioned for histological and image analysis. VEGF was detected by immunohistochemistry. RESULTS: Seven days later, there was statistical significance between the percentage of the survival area of the flap between the experimental group (70.432 +/- 3.867)% and the control group (50.498 +/- 2.346)% (P < 0.05). In the middle portion, edema and infiltration of tissue in the experimental group were reduced than those of the control group, and new blood vessels increased in the experimental group (P < 0.05). A statistical significance of the expression of VEGF was detected between experimental group (4867.31 +/- 452.36) and control group (2387.45 +/- 768.46) (P < 0.05). CONCLUSION: Ixeri sonhifolia injection can promote the survival of random skin flap by increasing the quantity of capillary, reducing inflammatory infiltration of Europhiles and increasing the expression of VEGF, which promote a new approaching for the transpanting of the random flap research.