Effects of Tuoli Xiaodusan on Ischemia-Reperfusion Injury of Rat Skin Flaps by Regulating NF-κB Signaling Pathway
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摘要:
目的 探讨托里消毒散对大鼠皮瓣缺血再灌注损伤的影响及其潜在机制。 方法 大鼠随机分为假手术组(Sham组)、模型组(Model组)、托里消毒散高剂量组(MDX-H组)和托里消毒散低剂量组(MDX-L组), 每组10只。大鼠背部皮瓣模型构建成功后, 立即给予药物灌胃处理,每日1次, 连续14 d。观察术后各组大鼠皮瓣变化情况, 并于术后第14天测定各组大鼠皮瓣成活率; HE染色观察大鼠皮瓣组织病理学变化; Western blot检测大鼠皮瓣组织p-p65和p-IκBα蛋白表达;ELISA法检测TNF-α、IL-1β、IL-6细胞因子的表达情况;通过Ki67和CD31免疫组化染色观察表皮基底层细胞增殖及血管再生情况。 结果 与Model组相比, MDX-H组与MDX-L组术后14 d出现少量水肿, 有少量炎性液体渗出, 脱痂时间提前, 皮瓣缺血坏死情况得到明显改善, 皮瓣坏死面积显著减少, 大鼠皮瓣成活率明显提高(P < 0.01)。此外, 托里消毒散可明显改善大鼠背部皮瓣缺血再灌注损伤组织病理形态, 降低p-p65和p-IκBα蛋白表达(P < 0.001), 降低血清中TNF-α、IL-1β、IL-6炎性因子水平(P < 0.05,P < 0.01,P < 0.001,P < 0.000 1)。Ki67和CD31的差异也提示托里消毒散治疗加快了缺血皮瓣损伤后的再上皮化和血管的形成。 结论 托里消毒散通过调控NF-κB信号通路、加速上皮化和血管生成, 发挥改善皮瓣缺血再灌注损伤的作用。 Abstract:OBJECTIVE To explore the effect of Tuoli Xiaodusan (MDX) on ischemia-reperfusion injury of rat skin flaps and its potential mechanism. METHODS Rats were randomly divided into sham operation group (Sham group), Model group, MDX high-dose group (MDX-H group) and MDX low-dose group (MDX-L group), with 10 rats in each group. After the rat back skin flap model was successfully constructed, the drug was administered by gavage immediately, once a day for 14 consecutive days. The changes of rat skin flaps in each group after surgery were observed, and the survival rate of rat skin flaps in each group was measured on the 14th day after surgery; the histopathological changes of rat skin flaps were observed by HE staining; the protein expression of p-p65 and p-IκBα in the rat skin flap tissue was detected by Western blot; ELISA method was used to detect the expression of TNF-α, IL-1β, and IL-6 cytokines; Ki67 and CD31 immunohistochemical staining were used to observe epidermal basal layer cell proliferation and vascular regeneration. RESULTS Compared with Model group, MDX-H group and MDX-L group had a small amount of edema and inflammatory fluid exudation after surgery, and the scab removal time was advanced; the ischemic necrosis of the skin flap was significantly improved, the area of skin flap necrosis was significantly decreased, and the survival rate of rat skin flaps was significantly increased (P < 0.01). In addition, MDX could significantly improve the pathological morphology of ischemia-reperfusion injury in rat back skin flaps, reduce the expression of p-p65 and p-IκBα proteins (P < 0.001), and decrease the levels of TNF-α, IL-1β, IL-6 inflammatory factor levels (P < 0.05, P < 0.01, P < 0.001, P < 0.000 1). The differences in Ki67 and CD31 also suggested that treatment with MDX accelerate re-epithelialization and blood vessel formation after ischemic flap injury. CONCLUSION MDX plays a role in improving ischemia-reperfusion injury of skin flaps by regulating the NF-κB signaling pathway and accelerating epithelialization and angiogenesis. -
表 1 各组大鼠皮瓣成活率比较(x±s,%,n=10)
Table 1. Comparison of the survival rate of rat flaps in each group (x±s, %, n=10)
组别 成活率 Sham 组 94.55±3.31 Model 组 59.66±4.73** MDX-H 组 89.96±2.34# MDX-L 组 86.52±3.22# 注:与Sham组比较, **P < 0.01;与Model组比较, #P < 0.05。 -
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