考来烯胺联合UDCA减轻犬胆汁淤积所致急性肝损伤的研究
发布时间：2018-08-18 14:29
【摘要】：考来烯胺是一种阴离子树脂交换剂,通过在肠道内与胆汁酸结合,阻断胆汁酸肝肠循环,从而降低肝内胆汁酸浓度。熊去氧胆酸(UDCA)是一种亲水性胆汁酸,通过改变胆汁酸池组成,竞争抑制疏水性胆汁酸对肝细胞的毒性作用,促进肝内胆汁排出等多种机制,保护肝细胞,抑制肝细胞凋亡。为了研究考来烯胺与熊去氧胆酸联合使用对于犬良性胆管狭窄所致胆汁淤积性肝损伤的保护作用,本试验从以下几个方面对联合用药的疗效进行了评估,旨在为犬类临床应用提供指导。试验Ⅰ犬良性胆管狭窄模型的建立本试验选取18只体重约为5kg的健康成年犬,随机均分为正常对照组(N组)、假手术组(S组)、良性胆管狭窄组(BBS组)。BBS组犬采用胆总管不完全结扎的方法建立良性胆管狭窄模型,S组仅分离胆总管,N组不做任何处理。试验结果显示,S组与N组在临床表现,血清生化指标、抗氧化指标以及肝组织抗氧化指标上,皆无明显差异(p0.05)。BBS组于造模后,血清生化指标ALT、AST、ALP、GGT、TB、DB、TBA水平以及血清抗氧化指标MDA、GST水平都出现快速升高,血清抗氧化指标SOD、T-AOC快速下降。各项血清指标随时间变化趋势不同,但皆与N组、S组间存在显著差异(p0.05)。术后14天检测肝组织抗氧化指标,BBS组肝组织MDA水平升高,而SOD、T-AOC、GST水平降低,与N组、S组间皆差异显著(p0.05)。组织病理学检查,BBS组出现广泛的肝细胞空泡变形,胆小管内胆汁淤积。术后14天对BBS组犬进行胆管造影,结果显示胆总管出现狭窄,但未形成完全阻塞。试验中未出现犬只死亡。综上所述,胆总管不完全结扎法能够良好地模拟犬良性胆管狭窄时胆汁淤积以及急性肝脏损伤情况。方法简单,并发症少,死亡率低,便于推广。试验Ⅱ考来烯胺联合熊去氧胆酸盐减轻犬胆汁淤积所致肝损伤的研究本试验选取24只体重约为5kg的健康成年犬,随机均分为对照组、考来烯胺组组(C组)、熊去氧胆酸组(UDCA组)、联合用药组(联合组)。四组犬皆按试验I中胆总管不完全结扎法建立良性胆管狭窄模型。术后对照组不予治疗,C组每日口服4g考来烯胺,UDCA组每日口服15mg/kg熊去氧胆酸,联合组于不同时段分别口服4g考来烯胺及15mg/kg熊去氧胆酸。于术前及术后第1、3、5、7、10、14天连续监测各组血清生化指标及血清抗氧化指标,并于第14天测定肝组织抗氧化指标。结果显示三组均能一定程度上减轻胆汁淤积及肝损伤。联合组血清ALT、AST、ALP、GGT、TB、DB、TBA水平于各时段皆在治疗组中处于较低水平;联合组血清及肝组织抗氧化指标MDA水平低于C组、UDCA组,而SOD、T-AOC水平则高于C组、UDCA组。联合组血清GST水平低于C组、UDCA组;而肝组织GST水平高于C组、UDCA组。组织病理学检查,联合组肝细胞肿胀、变性及胆汁淤积程度明显低于C组及UDCA组。试验过程无犬只死亡。综上所述,考来烯胺、熊去氧胆酸及考来烯胺联合熊去氧胆酸三种方法都能一定程度减轻良性胆管狭窄时犬胆汁淤积及肝损伤。而联合用药组胆汁淤积、肝损伤程度最轻,抗氧化效果最好,效果明显优于两种药物单独使用。
[Abstract]:Colineamine is an anionic resin exchanger that interrupts the hepatointestinal circulation of bile acids by binding to bile acids in the intestine, thereby reducing the concentration of bile acids in the liver. Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid that competes to inhibit the toxicity of hydrophobic bile acids to hepatocytes by altering the composition of bile acid pools and promoting intrahepatic bile. In order to study the protective effect of combined use of colineamine and ursodeoxycholic acid on bile duct stenosis-induced cholestasis-induced liver injury in dogs, the efficacy of combined use of colineamine and ursodeoxycholic acid was evaluated in order to provide guidance for clinical application in dogs. Establishment of benign biliary stricture model in dogs in test I. Eighteen healthy adult dogs weighing about 5 kg were randomly divided into normal control group (N group), sham operation group (S group) and benign biliary stricture group (BBS group). The results showed that there was no significant difference between S group and N group in clinical manifestations, serum biochemical indicators, antioxidant indicators and liver tissue antioxidant indicators (p0.05). BBS group after modeling, serum biochemical indicators ALT, AST, ALP, GGT, TB, DB, TBA levels and serum antioxidant indicators MDA, GST levels were increased rapidly, serum antioxidant activities were increased. The levels of SOD, T-AOC and GST in liver tissue of BBS group were higher than those of N group and S group (p0.05). The levels of SOD, T-AOC and GST in liver tissue of BBS group were lower than those of N group and S group (p0.05). Extensive hepatocyte vacuoles were deformed and cholestasis was found in the bile ducts. Cholangiography was performed 14 days after operation in BBS dogs. The results showed that the common bile duct was narrow but not completely obstructed. There was no death in the trial. In summary, the incomplete ligation of the common bile duct can well simulate the bile stasis and acute hepatic stenosis in dogs with benign bile duct stenosis. The method is simple, the complications are few, the mortality is low, easy to promote. Test II Colineamine combined with ursodeoxycholate to alleviate liver injury caused by cholestasis in dogs. 24 healthy adult dogs weighing about 5 kg were randomly divided into control group, colineamine group (C group), ursodeoxycholic acid group (UDCA group), combined use. Benign biliary stricture models were established by incomplete ligation of the common bile duct in test I. The control group was not treated after operation. The C group was orally administered 4 g colineamine daily. The UDCA group was orally administered 15 mg/kg ursodeoxycholic acid. The combined group was orally administered 4 g colineamine and 15 mg/kg ursodeoxycholic acid at different time points. Serum biochemical and antioxidant indexes were continuously monitored on day 1, 3, 5, 7, 10 and 14, and liver tissue antioxidant indexes were measured on day 14. The results showed that the three groups could alleviate cholestasis and liver injury to some extent. The levels of serum GST in combined group were lower than those in group C and UDCA, while the levels of SOD and T-AOC were higher than those in group C and UDCA. The levels of liver GST in combined group were higher than those in group C and UDCA. Histopathological examination showed that the degree of hepatocellular swelling, degeneration and cholestasis in combined group were lower than those in group C and UDCA. In summary, three methods, including colineamine, ursodeoxycholic acid and colineamine combined with ursodeoxycholic acid, can alleviate bile stasis and liver injury in dogs with benign biliary stricture to some extent.
【学位授予单位】：南京农业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S858.292
[Abstract]:Colineamine is an anionic resin exchanger that interrupts the hepatointestinal circulation of bile acids by binding to bile acids in the intestine, thereby reducing the concentration of bile acids in the liver. Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid that competes to inhibit the toxicity of hydrophobic bile acids to hepatocytes by altering the composition of bile acid pools and promoting intrahepatic bile. In order to study the protective effect of combined use of colineamine and ursodeoxycholic acid on bile duct stenosis-induced cholestasis-induced liver injury in dogs, the efficacy of combined use of colineamine and ursodeoxycholic acid was evaluated in order to provide guidance for clinical application in dogs. Establishment of benign biliary stricture model in dogs in test I. Eighteen healthy adult dogs weighing about 5 kg were randomly divided into normal control group (N group), sham operation group (S group) and benign biliary stricture group (BBS group). The results showed that there was no significant difference between S group and N group in clinical manifestations, serum biochemical indicators, antioxidant indicators and liver tissue antioxidant indicators (p0.05). BBS group after modeling, serum biochemical indicators ALT, AST, ALP, GGT, TB, DB, TBA levels and serum antioxidant indicators MDA, GST levels were increased rapidly, serum antioxidant activities were increased. The levels of SOD, T-AOC and GST in liver tissue of BBS group were higher than those of N group and S group (p0.05). The levels of SOD, T-AOC and GST in liver tissue of BBS group were lower than those of N group and S group (p0.05). Extensive hepatocyte vacuoles were deformed and cholestasis was found in the bile ducts. Cholangiography was performed 14 days after operation in BBS dogs. The results showed that the common bile duct was narrow but not completely obstructed. There was no death in the trial. In summary, the incomplete ligation of the common bile duct can well simulate the bile stasis and acute hepatic stenosis in dogs with benign bile duct stenosis. The method is simple, the complications are few, the mortality is low, easy to promote. Test II Colineamine combined with ursodeoxycholate to alleviate liver injury caused by cholestasis in dogs. 24 healthy adult dogs weighing about 5 kg were randomly divided into control group, colineamine group (C group), ursodeoxycholic acid group (UDCA group), combined use. Benign biliary stricture models were established by incomplete ligation of the common bile duct in test I. The control group was not treated after operation. The C group was orally administered 4 g colineamine daily. The UDCA group was orally administered 15 mg/kg ursodeoxycholic acid. The combined group was orally administered 4 g colineamine and 15 mg/kg ursodeoxycholic acid at different time points. Serum biochemical and antioxidant indexes were continuously monitored on day 1, 3, 5, 7, 10 and 14, and liver tissue antioxidant indexes were measured on day 14. The results showed that the three groups could alleviate cholestasis and liver injury to some extent. The levels of serum GST in combined group were lower than those in group C and UDCA, while the levels of SOD and T-AOC were higher than those in group C and UDCA. The levels of liver GST in combined group were higher than those in group C and UDCA. Histopathological examination showed that the degree of hepatocellular swelling, degeneration and cholestasis in combined group were lower than those in group C and UDCA. In summary, three methods, including colineamine, ursodeoxycholic acid and colineamine combined with ursodeoxycholic acid, can alleviate bile stasis and liver injury in dogs with benign biliary stricture to some extent.
【学位授予单位】：南京农业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S858.292
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