本文選題：重組水蛭素 + 撕脫皮瓣��； 參考：《瀘州醫(yī)學(xué)院》2012年碩士論文

【摘要】：目的：本實(shí)驗(yàn)通過建立大鼠背部撕脫皮瓣模型,研究重組水蛭素對撕脫皮瓣的保護(hù)作用及其機(jī)制,并探討重組水蛭素在臨床治療撕脫皮瓣的應(yīng)用前景。方法：選用健康SD大鼠108只,雌雄不拘,體重(250±50g),隨機(jī)分為3組：2個(gè)治療組(A組：重組水蛭素治療組,B組：低分子肝素治療組)和1個(gè)空白對照組(C組：注射用生理鹽水組),每組36只,按40mg/kg體重、1%戊巴比妥鈉腹腔注射麻醉,以背部中線為準(zhǔn),蒂位于頭側(cè),設(shè)計(jì)4cm×6cm大小的長方形隨意皮瓣,蒂部行保護(hù)性固定后,遠(yuǎn)端用縫線固定于細(xì)鐵棒后與精密稱量的重物相連,施予均為8kg的牽拉力,時(shí)間均為10秒形成撕脫皮瓣模型,遠(yuǎn)端游離緣稍加修剪后原位縫合。分別于術(shù)后即刻、12小時(shí)、24小時(shí)、48小時(shí)于皮瓣蒂部、距蒂部2cm和4cm三等分點(diǎn)皮下均勻注射重組水蛭素(2mg/lml/皮瓣)、低分子肝素(2mg/lml/皮瓣),空白對照組同法給予注射等量生理鹽水(1m1/皮瓣)。術(shù)后觀察皮瓣表面毛發(fā)生長情況,淤血、腫脹情況,皮瓣存活面積；分別檢測術(shù)后12h、1d、3d皮瓣遠(yuǎn)端組織內(nèi)P-選擇素含量,3d、5d、7d皮瓣遠(yuǎn)端組織內(nèi)VEGF含量；高倍鏡下觀察術(shù)后12h、1d、3d、5d、7d皮瓣遠(yuǎn)端組織病理切片內(nèi)毛細(xì)血管內(nèi)炎性細(xì)胞聚集情況及微血栓形成情況。 結(jié)果：1.大體觀察：術(shù)后12、24小時(shí)3組皮瓣均出現(xiàn)不同程度的發(fā)紺、腫脹,空白對照組較兩治療組發(fā)紺、腫脹嚴(yán)重；空白對照組淤滯帶界限較清晰,治療組淤滯帶界限不清。術(shù)后第5、7天,治療組皮瓣遠(yuǎn)端發(fā)紺、腫脹逐步消退,存活良好。空白對照組皮瓣遠(yuǎn)端和周緣仍較腫脹,且呈暗黑色,質(zhì)地變硬,表面毛發(fā)有脫失,未見毛細(xì)血管反應(yīng),趨向于壞死。術(shù)后第14天重組水蛭素組和低分子肝素組存活面積百分比分別為(86.07±1.30)%和(81.46±1.06)%,均比空白對照組(77.03±1.25)%高,有顯著性差異(p0.01),重組水蛭素組比低分子肝素組皮瓣成活率高,差異有統(tǒng)計(jì)學(xué)意義(p0.05)2.組織學(xué)觀察：術(shù)后12h：空白對照組鏡下見組織內(nèi)大片出血區(qū),充血、水腫明顯,有大量中性粒細(xì)胞浸潤；肝素組鏡下見組織內(nèi)片狀出血、充血,水腫較明顯,有較多中性粒細(xì)胞浸潤；重組水蛭素組鏡下見組織內(nèi)點(diǎn)狀出血,可見充血,水腫,少量中性粒細(xì)胞浸潤。1d：空白對照組鏡下見組織內(nèi)大片出血區(qū),充血、水腫明顯,中性粒細(xì)胞呈團(tuán)塊狀聚集,并可見早期壞死；肝素組鏡下見組織內(nèi)充血、水腫,中性粒細(xì)胞浸潤等均較明顯；重組水蛭素組鏡下見組織內(nèi)充血、水腫,可見數(shù)量不等的中性粒細(xì)胞散在存在。3d：空白對照組鏡下見組織內(nèi)大片出血,淤血明顯,大量形成炎性肉芽組織,其中可見中性粒細(xì)胞散在存在；肝素組鏡下見組織內(nèi)淤血、水腫,有炎性肉芽組織形成,可見中性粒細(xì)胞散在分布；重組水蛭素組鏡下見組織內(nèi)散在淤血,出血少見,炎性肉芽組織形成,散在的少量中性粒細(xì)胞。5d：空白對照組鏡下可見少量片狀出血、淤血,可見微血栓形成,炎性肉芽組織水腫；肝素組鏡下見少量淤血、水腫,炎性肉芽組織較成熟；重組水蛭素組鏡下見少量淤血,炎性肉芽組織成熟。7d：空白對照組鏡下見組織內(nèi)微血栓形成,毛細(xì)血管閉塞,新生毛細(xì)血管少；肝素組鏡下見組織內(nèi)少量微血栓形成,有新生毛細(xì)血管；重組水蛭素組鏡下見組織內(nèi)新生血管增生活躍,肉芽組織成熟。3.P-選擇素含量檢測(pg／m1)：術(shù)后第12小時(shí)、1天、3大,重組水蛭素組與低分子肝素組P-選擇素含量分別為(129.740±12.302)與(151.584±12.409)(111.030±6.824)與(134.434±8.707)、(101.674±4.429)與(118.308±7.535),其對應(yīng)空白組為(196.034±18.442)(162.087±14.485)、(132.473±8.142),第12小時(shí)、1天、3天重組水蛭素組與低分子肝素組和空白對照組之間差異有統(tǒng)計(jì)學(xué)意義(P0.05)。4.VEGF含量檢測：術(shù)后第3、5、7天,重組水蛭素組與低分子肝素組VEGF含量分別為(212.507±15.096)與(158.733±15.311)、(214.010±13.811)與(167.134±11.455)、(218.093±13.464)與(177.484±8.183),其對應(yīng)空白組為(120.454±7.575)、(130.133±19.159)、(133.800±4.882),第3、5、7天重組水蛭素組與低分子肝素組和空白對照組之間差異有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論：局部注射重組水蛭素能有效抑制P-選擇素的生成,減少炎性細(xì)胞的聚集,阻斷微血栓的形成,改善撕脫皮瓣局部缺血、缺氧狀態(tài)；減弱內(nèi)皮細(xì)胞的損傷,促進(jìn)VEGF的表達(dá),刺激新生毛細(xì)血管增生,提高撕脫皮瓣的存活率。
[Abstract]:Objective: To study the protective effect of recombinant hirudin on the avulsion flap and its mechanism, and to explore the prospect of recombinant hirudin in the treatment of avulsion flap. Methods: 108 healthy SD rats were selected and divided into 3 groups randomly: 2 groups (group A: 2). The recombinant hirudin group, B group, low molecular weight heparin treatment group and 1 blank control group (group C: saline group), 36 rats in each group, with 40mg/kg weight, 1% pentobarbital sodium intraperitoneal injection, the middle back line as the criterion, the pedicle at the head side, and the design of 4cm x 6cm large rectangular free flap, the pedicle was protected and distal to the distal end. The stitches were attached to the weight of the fine weight after the stitches were fixed to the fine iron rod. The pulling force was given to 8kg. The time was 10 seconds to form a rip flap model, and the distal free margin was sutured after a little pruning. The pedicle of the flap was 12 hours, 24 hours and 48 hours after the operation, and the recombinant hirudin was injected subcutaneously from the pedicle of the pedicle, 2cm and 4cm three. 2mg/lml/ skin flap), low molecular weight heparin (2mg/lml/ flap), blank control group was given equal amount of saline injection (1m1/ flap) with the same method. After the operation, the hair growth, congestion, swelling, and the survival area of the skin flap were observed. The content of P- selectin in the distal tissue of 12h, 1D, 3D flaps after the operation was detected respectively, 3D, 5D, 7d skin flap in the distal tissue of the flap. The volume of inflammatory cells and the formation of microthrombosis in the distal sections of 12h, 1D, 3D, 5D and 7d were observed at high magnification.
Results: 1. gross observation: 12,24 hours after operation, 3 groups of skin flaps were cyanosis to different degrees, swelling, the blank control group was cyanosis and severe swelling compared with the two treatment group; the limit of Stasis Zone in the blank control group was clearer and the Stasis Zone of the treatment group was not clear. After the operation on day 5,7, the distal cyanosis, swelling gradually subsided, and the survival was good. The distal and peripheral skin of the skin flap were still swollen, dark black, the texture became hard, the surface hair was lost and no capillary reaction was found. The survival area percentage of the recombinant hirudin group and low molecular weight heparin group was (86.07 + 1.30)% and (81.46 + 1.06)%, respectively, fourteenth days after the operation, which were all higher than that in the blank control group (77.03 + 1.25)%. The survival rate of the flaps in the recombinant hirudin group was higher than that of the low molecular weight heparin group (P0.01). The difference was statistically significant (P0.05) 2. histological observation: after the operation, 12h: the blank control group showed massive hemorrhage area under the microscope, hyperemia, edema obviously, and a large number of neutrophils infiltration. The heparin group was seen under the heparin group the bleeding, congestion and edema were obvious under the heparin group. In the recombinant hirudin group, there was a lot of neutrophils infiltration, and the recombinant hirudin group showed punctate hemorrhage in the tissue under the microscope. There was congestion, edema, and a small amount of neutrophils infiltrating.1d. The blank control group was seen under the microscope, with massive hemorrhage area, congestive, edema, neutrophils aggregation, and early necrosis. Edema, neutrophils infiltration and so on were obvious. The recombinant hirudin group showed hyperemia, edema, and quantity of neutrophils scattered in the presence of.3d: in the blank control group, large hemorrhage in the tissue was seen under the microscope, the blood was obvious, and a large number of inflammatory granulation tissues were formed, and the neutrophils were found in the presence of neutrophils; the heparin group was under the microscope. There was blood, edema, and inflammatory granulation tissue in the tissue, and the neutrophils were scattered in the tissue, and the recombinant hirudin group was found to be scattered in the tissues and scattered in the tissues. The hemorrhage was rare, the inflammatory granulation tissue was formed, and a small amount of neutrophils scattered in.5d were found in the blank control group. In the heparin group, a small amount of congestion, edema, and inflammatory granulation tissue were more mature in the heparin group. The recombinant hirudin group showed a small amount of blood stasis and the inflammatory granulation tissue matured.7d. The microthrombus was formed in the blank control group, and the capillary was obliterated and the newborn capillaries were few. In the recombinant hirudin group, the recombinant hirudin group was found to be active in neovascularization and to detect the content of.3.P- selectin in granulation tissue (PG / M1): Twelfth hours, 1 days, 3, and P- selectin in the recombinant hirudin group and low molecular weight heparin group (129.740 + 12.302) and (151.584 + 12.409) (111.030 + 6.824) and 134.434 + 8.707), (101.674 + 4.429) and (118.308 + 7.535), the corresponding blank group was (196.034 + 18.442) (162.087 + 14.485), (132.473 + 8.142), Twelfth hours, 1 days, the difference between the recombinant hirudin group and the low molecular weight heparin group and the blank control group was statistically significant (P0.05).4.VEGF content detection: after 3,5,7 day after operation, the recombinant hirudin group and the low level The content of VEGF in the molecular heparin group was (212.507 + 15.096) and (158.733 + 15.311), (214.010 + 13.811) and (167.134 + 11.455), (218.093 + 13.464) and (177.484 + 8.183), and the corresponding blank group was (120.454 + 11.455). The difference between the recombinant hirudin group and the low molecular weight heparin group and the blank control group was poor. P0.05. Conclusion: local injection of recombinant hirudin can effectively inhibit the formation of P- selectin, reduce the accumulation of inflammatory cells, block the formation of microthrombus, improve local ischemia and hypoxia, weaken the damage of endothelial cells, promote the expression of VEGF, stimulate the proliferation of newborn capillaries, and increase the skin flap of the capillaries. The survival rate.
【學(xué)位授予單位】：瀘州醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R641;R-332

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