Abstract：
BACKGROUND: 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.
OBJECTIVE: To explore the potential of L-borneol to promote skin flap survival and elucidate the underlying mechanisms.
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)-1β, 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.
CONCLUSIONS: The study shows that L-borneol may promote skin flap survival by inhibiting HIF-1α/NF-κB pathway.
OBJECTIVE: To explore the potential of L-borneol to promote skin flap survival and elucidate the underlying mechanisms.
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)-1β, 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.
CONCLUSIONS: The study shows that L-borneol may promote skin flap survival by inhibiting HIF-1α/NF-κB pathway.
摘要：
背景：皮瓣在外科重建中的临床应用经常受到远处坏死发生的阻碍。L-冰片在中药中表现出生肌特性，并在临床中用于促进伤口愈合和中风等病症。然而，冰片发挥保护皮瓣存活作用的确切机制尚不清楚。
目的：探讨L-冰片促进皮瓣成活的潜能，并阐明其作用机制。
方法：将36只雄性SD大鼠随机分为3组：高剂量组（每天200mg/kgL-冰片），低剂量（50毫克/千克/天），对照组(相同体积的溶剂)。在每只老鼠中，构建了尺寸为3×9厘米的改良矩形McFarlane皮瓣模型。每天进行L-冰片或溶剂的胃内给药。皮瓣被分成三个大小相等的正方形部分，即I区（近区），II区（中间区），和III区（远端区）。生存率被量化，在手术后的第七天评估每个皮瓣的组织学状态。使用氧化铅/明胶血管造影术评估血管生成，而游离皮瓣的血流评估是使用激光多普勒血流成像进行的。使用水溶性四唑盐8方法检测超氧化物歧化酶活性。血管内皮生长因子的数量，白细胞介素（IL）-1β，使用免疫组织化学测定IL-6和肿瘤坏死因子-α。核转录因子-κB的水平，缺氧诱导因子-1,B细胞淋巴瘤-2(BCL-2),用蛋白质印迹技术测定BCL-2相关X(BAX)。
结果：用化合物治疗后，皮瓣存活率显着提高，中性粒细胞募集和释放增强。促进了血管生成。L-冰片通过增加超氧化物歧化酶活性和降低丙二醛含量来保护免受氧化应激。下调缺氧诱导因子核转录因子-κB通路,导致多种炎症因子的抑制。同时,促进血管内皮生长因子和BCL-2的表达。
结论：研究表明，L-冰片可能通过抑制HIF-1α/NF-κB通路促进皮瓣存活。
目的：探讨L-冰片促进皮瓣成活的潜能，并阐明其作用机制。
方法：将36只雄性SD大鼠随机分为3组：高剂量组（每天200mg/kgL-冰片），低剂量（50毫克/千克/天），对照组(相同体积的溶剂)。在每只老鼠中，构建了尺寸为3×9厘米的改良矩形McFarlane皮瓣模型。每天进行L-冰片或溶剂的胃内给药。皮瓣被分成三个大小相等的正方形部分，即I区（近区），II区（中间区），和III区（远端区）。生存率被量化，在手术后的第七天评估每个皮瓣的组织学状态。使用氧化铅/明胶血管造影术评估血管生成，而游离皮瓣的血流评估是使用激光多普勒血流成像进行的。使用水溶性四唑盐8方法检测超氧化物歧化酶活性。血管内皮生长因子的数量，白细胞介素（IL）-1β，使用免疫组织化学测定IL-6和肿瘤坏死因子-α。核转录因子-κB的水平，缺氧诱导因子-1,B细胞淋巴瘤-2(BCL-2),用蛋白质印迹技术测定BCL-2相关X(BAX)。
结果：用化合物治疗后，皮瓣存活率显着提高，中性粒细胞募集和释放增强。促进了血管生成。L-冰片通过增加超氧化物歧化酶活性和降低丙二醛含量来保护免受氧化应激。下调缺氧诱导因子核转录因子-κB通路,导致多种炎症因子的抑制。同时,促进血管内皮生长因子和BCL-2的表达。
结论：研究表明，L-冰片可能通过抑制HIF-1α/NF-κB通路促进皮瓣存活。
