考來烯胺聯(lián)合UDCA減輕犬膽汁淤積所致急性肝損傷的研究
發(fā)布時間：2018-08-18 14:29
【摘要】：考來烯胺是一種陰離子樹脂交換劑,通過在腸道內(nèi)與膽汁酸結(jié)合,阻斷膽汁酸肝腸循環(huán),從而降低肝內(nèi)膽汁酸濃度。熊去氧膽酸(UDCA)是一種親水性膽汁酸,通過改變膽汁酸池組成,競爭抑制疏水性膽汁酸對肝細(xì)胞的毒性作用,促進(jìn)肝內(nèi)膽汁排出等多種機(jī)制,保護(hù)肝細(xì)胞,抑制肝細(xì)胞凋亡。為了研究考來烯胺與熊去氧膽酸聯(lián)合使用對于犬良性膽管狹窄所致膽汁淤積性肝損傷的保護(hù)作用,本試驗(yàn)從以下幾個方面對聯(lián)合用藥的療效進(jìn)行了評估,旨在為犬類臨床應(yīng)用提供指導(dǎo)。試驗(yàn)Ⅰ犬良性膽管狹窄模型的建立本試驗(yàn)選取18只體重約為5kg的健康成年犬,隨機(jī)均分為正常對照組(N組)、假手術(shù)組(S組)、良性膽管狹窄組(BBS組)。BBS組犬采用膽總管不完全結(jié)扎的方法建立良性膽管狹窄模型,S組僅分離膽總管,N組不做任何處理。試驗(yàn)結(jié)果顯示,S組與N組在臨床表現(xiàn),血清生化指標(biāo)、抗氧化指標(biāo)以及肝組織抗氧化指標(biāo)上,皆無明顯差異(p0.05)。BBS組于造模后,血清生化指標(biāo)ALT、AST、ALP、GGT、TB、DB、TBA水平以及血清抗氧化指標(biāo)MDA、GST水平都出現(xiàn)快速升高,血清抗氧化指標(biāo)SOD、T-AOC快速下降。各項(xiàng)血清指標(biāo)隨時間變化趨勢不同,但皆與N組、S組間存在顯著差異(p0.05)。術(shù)后14天檢測肝組織抗氧化指標(biāo),BBS組肝組織MDA水平升高,而SOD、T-AOC、GST水平降低,與N組、S組間皆差異顯著(p0.05)。組織病理學(xué)檢查,BBS組出現(xiàn)廣泛的肝細(xì)胞空泡變形,膽小管內(nèi)膽汁淤積。術(shù)后14天對BBS組犬進(jìn)行膽管造影,結(jié)果顯示膽總管出現(xiàn)狹窄,但未形成完全阻塞。試驗(yàn)中未出現(xiàn)犬只死亡。綜上所述,膽總管不完全結(jié)扎法能夠良好地模擬犬良性膽管狹窄時膽汁淤積以及急性肝臟損傷情況。方法簡單,并發(fā)癥少,死亡率低,便于推廣。試驗(yàn)Ⅱ考來烯胺聯(lián)合熊去氧膽酸鹽減輕犬膽汁淤積所致肝損傷的研究本試驗(yàn)選取24只體重約為5kg的健康成年犬,隨機(jī)均分為對照組、考來烯胺組組(C組)、熊去氧膽酸組(UDCA組)、聯(lián)合用藥組(聯(lián)合組)。四組犬皆按試驗(yàn)I中膽總管不完全結(jié)扎法建立良性膽管狹窄模型。術(shù)后對照組不予治療,C組每日口服4g考來烯胺,UDCA組每日口服15mg/kg熊去氧膽酸,聯(lián)合組于不同時段分別口服4g考來烯胺及15mg/kg熊去氧膽酸。于術(shù)前及術(shù)后第1、3、5、7、10、14天連續(xù)監(jiān)測各組血清生化指標(biāo)及血清抗氧化指標(biāo),并于第14天測定肝組織抗氧化指標(biāo)。結(jié)果顯示三組均能一定程度上減輕膽汁淤積及肝損傷。聯(lián)合組血清ALT、AST、ALP、GGT、TB、DB、TBA水平于各時段皆在治療組中處于較低水平;聯(lián)合組血清及肝組織抗氧化指標(biāo)MDA水平低于C組、UDCA組,而SOD、T-AOC水平則高于C組、UDCA組。聯(lián)合組血清GST水平低于C組、UDCA組;而肝組織GST水平高于C組、UDCA組。組織病理學(xué)檢查,聯(lián)合組肝細(xì)胞腫脹、變性及膽汁淤積程度明顯低于C組及UDCA組。試驗(yàn)過程無犬只死亡。綜上所述,考來烯胺、熊去氧膽酸及考來烯胺聯(lián)合熊去氧膽酸三種方法都能一定程度減輕良性膽管狹窄時犬膽汁淤積及肝損傷。而聯(lián)合用藥組膽汁淤積、肝損傷程度最輕,抗氧化效果最好,效果明顯優(yōu)于兩種藥物單獨(dú)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.
【學(xué)位授予單位】：南京農(nóng)業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：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.
【學(xué)位授予單位】：南京農(nóng)業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：S858.292
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