良性胆管狭窄胆肠吻合术疗效分析及曲安奈德缓释膜特性
发布时间：2018-11-10 10:09
【摘要】：目的：胆道良性狭窄的处理是肝胆外科的一大难题。胆肠吻合术、自体组织修复术、内镜支架置入术、内镜乳头括约肌切开术等都可以作为良性胆管狭窄的治疗策略。在瘢痕的非手术治疗中,类固醇激素是一种疗效确切的药物。曲安奈德缓释膜片(Triamcinolone acetonide-chitosan sustained-released membrane, TASM)是我课题组前期自主研制的载药缓释膜片,并已证实TASM具有：1)能够减少人良性胆管瘢痕成纤维细胞中TGF-β1、α-SMA的表达。2)TASM在胆管损伤后的瘢痕形成中具有一定的防治作用。因此,]TASM为BBS防治提供了一种新的治疗手段。本实验旨在：1)通过系统性回顾分析昆明医科大学第二附属医院肝胆外科2010年1月至2014年6月的良性胆管狭窄85例病历资料分析BBS的主要病因以及胆肠吻合术治疗BBS的临床疗效。2)研究TASM的理化性质,评价其在动物体内的生物学特性,讨论其作为胆道瘢痕性狭窄手术植入物的可行性。实验方法：第一章良性胆管狭窄胆肠吻合术的疗效分析。通过回顾性分析昆明医科大学第二附属医院肝胆外科2010年1月至2014年6月的BBS病历资料分析BBS的病因及胆肠吻合术的临床疗效。第二章曲安奈德缓释膜片的理化性质测定试验。对TASM的水分、灰分、PH值、电导率、旋转粘度、重金属铅含量、蛋白质含量、吸水率与溶胀比进行试验测定。第三章曲安奈德缓释膜片的生物学特性的动物体内实验。通过皮内刺激实验、急性肝毒性实验和体内植入实验评价其肝毒性、生物组织相容性以及探讨其作为体内植入物的可行性。结论：1)本研究通过对BBS病历资料的回顾性研究发现：(1)良性胆管狭窄的主要病因为肝胆管结石,其次为医源性胆管损伤；(2)高胆红素血症是胆肠吻合术治疗BBS的独立危险因素；(3)胆肠吻合术后T管放置应遵循个体化原则；(4)合理的选择术式、彻底清除病灶、保持通畅引流及提高手术技术等是胆肠吻合术治疗BBS术后并发症发生的关键因素。2)本研究通过对TASM理化性质测定得出：(1)TASM水分及灰分含量低,保证了膜片质量,有利于其储存；(2)TASM的PH值接近于人体内环境PH值,有利于该膜片在生物体内利用；(3)曲安奈德缓释膜溶液属于O/W微乳,有利于曲安奈德药物的释放；(4)TASM所含重金属铅和蛋白质含量极低,可以安全应用于人体。(5)TASM具有较强的亲水性和优越的抗溶胀性,其化学性质稳定。3)本研究通过动物皮内刺激实验、急性肝毒性实验和体内植入实验证实：(1)TASM不会引起过度的炎症反应；(2)TASM和HPCTS均有较好的生物组织相容性,但是TASM的生物组织相容性较HPCTS更好。本实验为TASM作为胆道瘢痕性狭窄手术植入物的可行性提供了一定的理论依据。
[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 伪-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.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R657.4
本文编号：2322153
[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 伪-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.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R657.4
【参考文献】
相关期刊论文 前1条
1 刘金钢,余云;胆道术后残余结石及再生结石的内镜治疗[J];中国实用外科杂志;2004年02期
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