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Research on the Effect of Increase of Phospholipid Secretion in Bile and Its Bile Duct Prevention after Liver Transplantation in Rat

Author: JiangWeiWei
Tutor: WangShuGuang
School: Third Military Medical University
Course: Surgery
Keywords: Liver transplantation Biliary complications Bile composition changes Simvastatin Phospholipid Multi - drug resistance -2
CLC: R657.3
Type: Master's thesis
Year: 2008
Downloads: 12
Quote: 0
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Abstract


Purpose biliary complications seriously affect the survival and quality of life of liver transplant recipients, recognized liver transplant weak link (Achilles'heel). With the improvement of biliary complications deepens the understanding of technology and surgical stapling, the declining incidence of biliary anastomotic complications caused by surgical technical reasons and the drainage tube-related complications, and non-surgical technical factors biliary complications still is one of the main factors restricting the long-term efficacy of liver transplantation. of 2% -19%. Despite the recognized cold preservation / reperfusion injury (CPRI) is the leading cause of morbidity, but the exact mechanism is unclear. Hydrophobic bile salts in the bile duct injury in recent years, attention has been paid. Hydrophobic bile salts can interfere with biofilm \Gall Yanchi more than 95% by hydrophobic bile salts. Under normal circumstances, the body having a set and a hydrophobic bile salts cytotoxic self-protection mechanism, such as phospholipids and bile formed micelles (micelle) to reduce its cytotoxic hydrophilic bile salts, bile contained through the enhancement of the stability of the cell membrane to cytotoxic against hydrophobic bile salts. In addition, the main component of the secretion of bile is completely dependent hepatocyte bile capillary surface hepatobiliary membrane transport proteins (HMTs) the abnormal, HMTs gene expression may lead to cholestasis and bile duct injury. Research suggests that liver transplantation phenomenon of imbalance in the composition of bile. The consolidated results of the research at home and abroad in recent years, \Therefore, we propose the following assumptions: If we can active control of the composition of bile, increase the proportion of bile phospholipids and hydrophilic bile salt and hydrophobic bile salts cytotoxicity, whether it helps to alleviate transplant hepatobiliary tree damage it? 3 - hydroxy-3 - methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (simvastatin) because of its main ingredients on blood lipids clear role and a good risk-benefit ratio of these drugs unique lipid-lowering benefits more widely applied. Some recent studies have found that statins phospholipid secretion in rat liver and gallbladder tube have a significant impact, more than five days of the long-term treatment can induce liver synthesis of phosphatidylcholine (PC) and promote the discharge of bile phospholipids, bile salts did not affect the secretion of [3]. Hydrophobic bile salts have strong cytotoxicity, plays an important role in the bile duct injury. Take the initiative to change the composition of bile, to prevent bile salts cytotoxicity of liver cells and biliary epithelial cells has important practical significance and clinical value. In this study intends to explore this prevention strategy as the main purpose, to establish a suitable for transplant hepatobiliary research in rat liver transplantation model, to investigate the variation experienced CPRI after transplantation of the main ingredients of the liver bile and bile duct injury, phospholipid transfer protein expression and function change research, to provide new ideas for the prevention of clinical transplantation biliary tract complications. Second, the method in order to validate our hypothetical, the experimental design is as follows: First, the establishment of a reconstruction of hepatic artery in rat liver transplantation model, set simvastatin feeding (experimental group), standard diet (control group) and sham group, experimental group and a control group of donor liver the experienced UW solution 12 hours save after implantation of the receptor, and after 14 days for the rat liver, blood and bile samples; Subsequently, the application of high performance liquid chromatography (HPLC) detection of bile samples bile salt composition and changes in circumstances, and further analysis of the changes in the bile and serum phospholipid (PL) and total bile acid (TBA), evaluated after simvastatin treatment, transplantation bile composition changes of the liver in rats; then observe the pathological changes of the liver tissue, and to explore the relationship between these changes and the secretion of bile phospholipids; Finally, using immunohistochemistry and real-time quantitative PCR method to detect phospholipid transfer protein expression changes of simvastatin on the transplanted liver phospholipids change mechanism. Results 1. Arterial reconstruction of hepatic artery in rat orthotopic liver transplantation model fit applied to the study of biliary complications, better maneuverability and repeatability; rat bile after simvastatin treatment in phospholipid composition was significantly increased compared with the sham group and control group was statistically significant (P lt; 0.05); bile in bile salt composition indirectly reduced the bile bile salt / phospholipid ratio, reducing cause transplant bile duct injury factors; 3 postoperative simvastatin treated rat serum bile zymography (r-GT, ALP) was significantly reduced, there is a statistically significant (P lt; 0.05); and this trend and the secretion of bile phospholipids was negatively correlated; 4 the liver tissues HE, Masson staining found obvious inflammatory response of the liver tissue of the control group, the bile duct was severely damaged, and accompanied by a large number of bile duct hyperplasia; simvastatin treatment group pathological changes compared with the control group slightly; 5. immunohistochemical methods phospholipid transfer protein (Mdr2 P-glycoprotein) expression in rat liver cell membrane simvastatin treatment group compared with the control group significantly increased, mainly located in the exchange district and around the portal vein area; Mdr2 P-glycoprotein of sham-operated rats only weak expression; Taqman probe real-time quantitative PCR detection Mdr2 mRNA expression also increased significantly in the simvastatin treated rats, and statistically significant (P lt; 0.05). Conclusion Simvastatin can effectively increase the phospholipid composition in rats after transplantation bile secretion of bile bile salts and bile acid composition has no effect, and can significantly reduce the bile bile salt / phospholipid ratio; 2. bile phospholipid composition increase significantly improved transplant liver function, reduce the pathological changes of the liver tissue, the effective protection of the transplant bile duct and liver tissue; the phospholipid secretion mechanism of this increase may Mdr2 gene regulation.

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