本文選題：負(fù)壓創(chuàng)面治療　切入點(diǎn)：糖尿病　出處：《第四軍醫(yī)大學(xué)》2013年碩士論文

【摘要】：研究背景及目的 隨著社會發(fā)展及人口老齡化，日常生活中急慢性創(chuàng)面的發(fā)生率也明顯增加。車禍或自然災(zāi)害等急性創(chuàng)傷因素往往導(dǎo)致皮膚軟組織缺損、肌腱或骨質(zhì)外露。這類創(chuàng)面的修復(fù)在臨床往往比較復(fù)雜，是臨床醫(yī)師面臨的挑戰(zhàn)之一。臨床常規(guī)的治療方法是經(jīng)創(chuàng)面準(zhǔn)備使創(chuàng)面形成健康的肉芽組織后行手術(shù)植皮或皮瓣移植來修復(fù)創(chuàng)面。濕敷換藥是最常用的創(chuàng)面準(zhǔn)備方法，通過創(chuàng)面濕敷換藥使創(chuàng)面形成新鮮的肉芽組織，提高植皮及皮瓣移植手術(shù)的成功率。但常規(guī)濕敷換藥要達(dá)到滿意的創(chuàng)基準(zhǔn)備要求需要耗費(fèi)較長的時(shí)間并且往往因?yàn)轭l繁換到給患者帶來不可避免的痛苦。對于一些伴有肌腱暴露的創(chuàng)面，簡單的濕敷換藥往往不能達(dá)到良好的創(chuàng)基準(zhǔn)備要求。 負(fù)壓創(chuàng)面治療技術(shù)（Negative Pressure Wound Therapy）又稱真空輔助閉合療法（VAC，Vacuum assisted closure），是近年來興起的一種促進(jìn)創(chuàng)面愈合的前沿技術(shù)并被廣泛應(yīng)用于臨床各種創(chuàng)面的治療，尤其是一些復(fù)雜難愈性創(chuàng)面的治療。負(fù)壓創(chuàng)面治療技術(shù)的概念是利用醫(yī)用多聚泡沫敷料及半透生物貼膜封閉創(chuàng)面后，利用引流管將創(chuàng)面敷料與負(fù)壓裝置連接達(dá)到治療創(chuàng)面的目的。既往研究表明負(fù)壓可以通過增加創(chuàng)面血流、促進(jìn)創(chuàng)面肉芽組織生長，減少細(xì)菌定植和繁殖及保持傷口環(huán)境濕潤。雖然NPWT已被廣泛應(yīng)用，但其作用的詳細(xì)分子機(jī)制目前仍不明確，尤其是關(guān)于其對創(chuàng)面血管新生過程的影響及機(jī)制的研究比較罕見。因此本課題擬以正常大鼠及糖尿病大鼠后背全層皮膚缺損創(chuàng)面為模型從功能上及組織病理結(jié)構(gòu)上驗(yàn)證NPWT對創(chuàng)面血管生成過程的影響，并探討部分分子機(jī)制。 方法 1.雄性SD大鼠40只，隨機(jī)分為治療組和對照組。大鼠后背正中偏上1cm處創(chuàng)建2cm×2cm大小全層皮膚缺損創(chuàng)面。對照組創(chuàng)面用醫(yī)用泡沫敷料包扎予以常規(guī)換藥，治療組創(chuàng)面用醫(yī)用泡沫敷料覆蓋后，每天予以4小時(shí)120mmHg的持續(xù)負(fù)壓治療，連續(xù)給予負(fù)壓治療7天。分別在術(shù)后1、3、7天檢測創(chuàng)面血液灌注情況，利用HE及免疫組化染色觀察創(chuàng)面血管生成狀況，PCR技術(shù)檢測創(chuàng)面組織血管形成調(diào)節(jié)因子的表達(dá)情況。 2.雄性SD大鼠60只，，隨機(jī)分成正常大鼠組和糖尿病大鼠組。糖尿病組大鼠經(jīng)腹腔單次注射鏈脲佐菌素誘導(dǎo)糖尿病模型，注射后48小時(shí)檢測大鼠尾靜脈血糖濃度，血糖濃度＞16.7mmol/L視為糖尿病模型建立。兩周后在兩組大鼠后背正中創(chuàng)建全層皮膚缺損模型，創(chuàng)面予以常規(guī)換藥。觀察兩組大鼠生活習(xí)性及大體表觀的變化。分別在術(shù)后1、3、7、14天計(jì)算比較兩組大鼠創(chuàng)面愈合率的差異。利用激光多普勒技術(shù)分別在術(shù)后1、3、7天檢測創(chuàng)面血流灌注狀況。 3.60只鏈脲佐菌素誘導(dǎo)的糖尿病大鼠，隨機(jī)分成治療組及對照組，在后背創(chuàng)建全層皮膚缺損創(chuàng)面。對照組創(chuàng)面予以常規(guī)換藥，對照組創(chuàng)面用醫(yī)用泡沫敷料覆蓋后，每天予以120mmHg持續(xù)負(fù)壓治療4小時(shí)，治療維持7天。分別在術(shù)后1、3、7天觀察創(chuàng)面血液灌注情況，創(chuàng)面組織做病理切片觀察創(chuàng)面血管形成狀況，利用PCR技術(shù)檢測創(chuàng)面血管形成調(diào)節(jié)因子的表達(dá)情況。 結(jié)果 1.與對照組相比，NPWT明顯增加了創(chuàng)面血流灌注量（P＜0.05）。創(chuàng)面血管密度在術(shù)后第3天明顯高于對照組（P＜0.05），術(shù)后第7天，NPWT治療組創(chuàng)面新生血管排列規(guī)律，管腔寬暢，而對照組排列紊亂，管腔迂曲。治療組創(chuàng)面血管生成的正性調(diào)節(jié)因子VEGF及Ang1在術(shù)后第3天明顯高于對照組（P＜0.05）。 2.與正常大鼠比較，糖尿病大鼠多飲、多尿及多食癥狀明顯，皮毛發(fā)黃，體重增加緩慢。創(chuàng)面愈合率在術(shù)后第3、7、14天明顯低于正常大鼠（P＜0.05）。創(chuàng)面血液灌注量術(shù)后第1、3、7天明顯低于對照組（P＜0.05）。 3.治療組創(chuàng)面血流灌注量在各時(shí)間點(diǎn)均高于對照組。術(shù)后第3天，治療組創(chuàng)面血管密度明顯高于對照組（P＜0.05），第七天創(chuàng)面血管密度在治療組及對照組間無明顯差別，但組織病理顯示治療組創(chuàng)面新生血管排列規(guī)律，管腔寬大通暢；術(shù)后第7天及14天創(chuàng)面血管形成負(fù)性調(diào)節(jié)因子Ang2在治療組明顯低于對照組（P＜0.05）。 結(jié)論 1. NPWT可以增加正常大鼠創(chuàng)面血流灌注，有益于創(chuàng)面血管生成過程。NPWT促進(jìn)創(chuàng)面血管生成的機(jī)制可能與上調(diào)促血管生成因子VEGF及Ang1的表達(dá)有關(guān)。 2.糖尿病大鼠創(chuàng)面血供不良，創(chuàng)面血管生成功能障礙可能是其創(chuàng)面難愈的原因之一。 3. NPWT可以改善糖尿病創(chuàng)面血液灌注，增加創(chuàng)面早期新生血管密度，有利于新生血管的成熟。對血管生成素及其受體通路的影響也是其可能的機(jī)制之一。
[Abstract]:Background and purpose of research
With the social development and population aging, the incidence of acute and chronic wounds in daily life also increased significantly. The accident or natural disasters and other factors often lead to acute traumatic skin and soft tissue defect, tendon or bone exposure. This type of wound repair in clinic is often more complex, is one of the challenges facing clinicians. Conventional treatment the method is to make the clinical wound wound to form a healthy granulation tissue were surgical skin grafting or flap to repair the wound. The wound wet dressing is the most commonly used preparation methods, formation of fresh granulation tissue through the wound wet dressing the wound, skin flap transplantation and improve the success rate of the operation. But the conventional wet dressing to achieve with the initial preparation requires longer time and often because of frequent change to bring patients the inevitable pain. For some with tendon exposed wound The surface, simple wet dressing often cannot achieve good initial preparation requirements.
Negative pressure wound therapy (Negative Pressure Wound Therapy) is also called vacuum assisted closure therapy (VAC Vacuum, assisted closure), is on the rise in recent years a cutting-edge technology to promote wound healing and is widely used in all kinds of clinical wound, especially in the treatment of some complicated wounds. The concept of negative pressure wound therapy is the use of medical poly foam dressing and semi permeable biological film wound closure, the drainage tube will wound dressings and negative pressure device is connected to the wound treatment. Previous study showed that negative pressure can increase blood flow through the wound, promote the growth of granulation tissue, reduce the bacterial colonization and reproduction and keep the wound moist environment. Although NPWT has been with wide application, but its molecular mechanism is still not clear, especially about its effects on wound angiogenesis and mechanism research Relatively rare. Therefore, we aim to verify the effects of NPWT on wound angiogenesis in normal rats and diabetic rats, and to explore some molecular mechanisms.
Method
1. of 40 male SD rats were randomly divided into treatment group and control group. The rats back at 1cm 2cm to create a partial median size of 2cm * full-thickness skin wounds. The wounds of control group with medical foam dressing treatment group received conventional dressing, wound covered with medical foam dressing, every day to 4 continuous negative pressure 120mmHg hours of treatment, continuous treatment for 7 days respectively. Given the negative pressure in 1,3,7 days after detection of wound blood perfusion, using HE and immunohistochemical staining to observe the wound angiogenesis, vascular wound tissue detection PCR technique to form expression regulator.
2. of 60 male SD rats were randomly divided into normal group and diabetic rats group. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin induced diabetic model of rats was detected 48 hours after injection of tail vein blood glucose concentration, glucose concentration, 16.7mmol/L as the diabetic model established after two weeks. In the back of the two groups of rats was created full-thickness skin defect model, wound dressing change. To observe two groups of rats living habits and generally apparent changes in 1,3,7,14 days after the operation respectively. Comparing the two groups of rats wound healing rate difference. Using laser Doppler technique in 1,3,7 days after detection of wound blood perfusion status.
Only 3.60 of diabetic rats induced by streptozotocin, were randomly divided into treatment group and control group, create full-thickness skin wounds in the back. The control group was given routine treatment, the control group was covered with medical foam dressing, every day to 120mmHg 4 hours of continuous negative pressure therapy, treatment lasted for 7 days. In operation after 1,3,7 days to observe the wound blood perfusion, wound tissue pathological section observation of wound angiogenesis, vascular wound detection using PCR technique to form the expression of regulatory factors.
Result
1. compared with the control group, NPWT significantly increased the wound blood perfusion (P < 0.05). Vascular density in third days after operation was significantly higher than the control group (P < 0.05), seventh days after operation, NPWT group wound angiogenesis arrangement rule of lumen spacious, while the control group arranged disorderly, lumen tortuous. The treatment group was wound angiogenesis regulatory factor VEGF and Ang1 in third days after operation was significantly higher than the control group (P < 0.05).
2., compared with the normal rats, diabetic rats had more symptoms of polyuria, polyuria and polyarthritis. Their hair was yellow and their weight gain was slow. The wound healing rate was significantly lower than that of the normal rats at 3,7,14 days after operation (P < 0.05). The blood perfusion volume of the wound was significantly lower than that of the control group at 1,3,7 days after operation (P < 0.05).
3. wound treatment group blood perfusion were higher than the control group at each time point. Third days after operation, wound treatment group vascular density was significantly higher than the control group (P < 0.05), seventh days of wound vascular density had no obvious difference between the treatment group and the control group, but the pathological change showed that treatment group wound neovascularization arrangement rule after seventh large lumen patency; and 14 days wound angiogenesis negative regulatory factor Ang2 in treatment group was significantly lower than the control group (P < 0.05).
conclusion
1. NPWT can increase the blood perfusion of normal rats, which is beneficial to the angiogenesis of wounds. The mechanism of.NPWT promoting angiogenesis is probably related to the up regulation of angiogenesis factors VEGF and Ang1 expression.
2. wound blood of diabetic rats for poor wound angiogenesis dysfunction may be one of the reasons for the wound healing.
3. NPWT can improve the blood perfusion of diabetic wound and increase the early neovascularization of the wound, which is beneficial to the maturation of new blood vessels. The effect of angiopoietin and its receptor pathway is also one of its possible mechanisms.

【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R641

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