【摘要】：目的：膽道良性狹窄的處理是肝膽外科的一大難題。膽腸吻合術、自體組織修復術、內鏡支架置入術、內鏡乳頭括約肌切開術等都可以作為良性膽管狹窄的治療策略。在瘢痕的非手術治療中,類固醇激素是一種療效確切的藥物。曲安奈德緩釋膜片(Triamcinolone acetonide-chitosan sustained-released membrane, TASM)是我課題組前期自主研制的載藥緩釋膜片,并已證實TASM具有：1)能夠減少人良性膽管瘢痕成纖維細胞中TGF-β1、α-SMA的表達。2)TASM在膽管損傷后的瘢痕形成中具有一定的防治作用。因此,]TASM為BBS防治提供了一種新的治療手段。本實驗旨在：1)通過系統(tǒng)性回顧分析昆明醫(yī)科大學第二附屬醫(yī)院肝膽外科2010年1月至2014年6月的良性膽管狹窄85例病歷資料分析BBS的主要病因以及膽腸吻合術治療BBS的臨床療效。2)研究TASM的理化性質,評價其在動物體內的生物學特性,討論其作為膽道瘢痕性狹窄手術植入物的可行性。實驗方法：第一章良性膽管狹窄膽腸吻合術的療效分析。通過回顧性分析昆明醫(yī)科大學第二附屬醫(yī)院肝膽外科2010年1月至2014年6月的BBS病歷資料分析BBS的病因及膽腸吻合術的臨床療效。第二章曲安奈德緩釋膜片的理化性質測定試驗。對TASM的水分、灰分、PH值、電導率、旋轉粘度、重金屬鉛含量、蛋白質含量、吸水率與溶脹比進行試驗測定。第三章曲安奈德緩釋膜片的生物學特性的動物體內實驗。通過皮內刺激實驗、急性肝毒性實驗和體內植入實驗評價其肝毒性、生物組織相容性以及探討其作為體內植入物的可行性。結論：1)本研究通過對BBS病歷資料的回顧性研究發(fā)現(xiàn)：(1)良性膽管狹窄的主要病因為肝膽管結石,其次為醫(yī)源性膽管損傷；(2)高膽紅素血癥是膽腸吻合術治療BBS的獨立危險因素；(3)膽腸吻合術后T管放置應遵循個體化原則；(4)合理的選擇術式、徹底清除病灶、保持通暢引流及提高手術技術等是膽腸吻合術治療BBS術后并發(fā)癥發(fā)生的關鍵因素。2)本研究通過對TASM理化性質測定得出：(1)TASM水分及灰分含量低,保證了膜片質量,有利于其儲存；(2)TASM的PH值接近于人體內環(huán)境PH值,有利于該膜片在生物體內利用；(3)曲安奈德緩釋膜溶液屬于O/W微乳,有利于曲安奈德藥物的釋放；(4)TASM所含重金屬鉛和蛋白質含量極低,可以安全應用于人體。(5)TASM具有較強的親水性和優(yōu)越的抗溶脹性,其化學性質穩(wěn)定。3)本研究通過動物皮內刺激實驗、急性肝毒性實驗和體內植入實驗證實：(1)TASM不會引起過度的炎癥反應；(2)TASM和HPCTS均有較好的生物組織相容性,但是TASM的生物組織相容性較HPCTS更好。本實驗為TASM作為膽道瘢痕性狹窄手術植入物的可行性提供了一定的理論依據。
[Abstract]:Objective: the management of benign biliary stricture is a difficult problem in hepatobiliary surgery. Cholangiojejunostomy, autogenous tissue repair, endoscopic stenting and endoscopic sphincterotomy can be used as treatment strategies for benign biliary stricture. Steroid hormones are an effective drug in the non-surgical treatment of scars. Triamcinolone acetonide sustained-release membrane (Triamcinolone acetonide-chitosan sustained-released membrane, TASM) was developed by our research group in the early stage, and it has been proved that TASM has the following properties: 1) it can reduce TGF- 尾 1 in human benign bile duct scar fibroblasts. The expression of 偽-SMA. 2) TASM plays a role in the prevention and treatment of scar formation after bile duct injury. Therefore, TASM provides a new treatment for the prevention and treatment of BBS. The purpose of this study was: 1) to analyze the main causes of BBS and cholangiojejunostomy in 85 cases of benign bile duct stricture from January 2010 to June 2014 in the second affiliated Hospital of Kunming Medical University. Clinical efficacy of BBS. 2) to study the physical and chemical properties of TASM, To evaluate its biological characteristics in vivo and to discuss its feasibility as surgical implants for biliary scar stenosis. Methods: chapter 1: analysis of the curative effect of benign biliary stricture cholangiojejunostomy. The etiology of BBS and the clinical effect of choledochojejunostomy in the second affiliated Hospital of Kunming Medical University from January 2010 to June 2014 were analyzed retrospectively. Chapter 2 the physical and chemical properties of triamcinolone acetonide sustained-release membrane. The water content, ash content, PH value, conductivity, rotational viscosity, heavy metal lead content, protein content, water absorption and swelling ratio of TASM were measured. Chapter 3 in vivo experiments on biological characteristics of triamcinolone acetonide sustained-release membranes. The intradermal stimulation test, acute hepatotoxicity test and in vivo implantation test were used to evaluate the hepatotoxicity, biocompatibility and the feasibility of using them as implants in vivo. Conclusion: 1) the main cause of benign bile duct stenosis is hepatolithiasis, followed by iatrogenic bile duct injury. (2) hyperbilirubinemia was an independent risk factor in the treatment of BBS by choledochojejunostomy, (3) T tube placement after choledochojejunostomy should follow the principle of individualization. (4) to select the operative method reasonably and remove the lesion completely. Keeping unobstructed drainage and improving surgical techniques are the key factors in the treatment of complications after choledochojejunostomy. 2) the physical and chemical properties of TASM were determined as follows: (1) the content of water and ash in TASM was low and the quality of membrane was ensured. Facilitate their storage; (2) the PH value of TASM is close to the PH value in human environment, which is beneficial to the use of triamcinolone acetonide in vivo, (3) triamcinolone acetonide sustained-release membrane solution belongs to O / W microemulsion, which is favorable for the release of triamcinolone acetonide (triamcinolone acetonide). (4) the content of lead and protein in TASM is very low, which can be safely used in human body. (5) TASM has strong hydrophilicity and excellent anti-swelling property, and its chemical property is stable. Acute hepatotoxicity test and in vivo implantation test confirmed that: (1) TASM did not cause excessive inflammatory reaction; (2) both TASM and HPCTS had good biocompatibility, but TASM had better biocompatibility than HPCTS. This experiment provides a theoretical basis for the feasibility of TASM as surgical implants for biliary scar stenosis.
【學位授予單位】：昆明醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R657.4

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