Mathison Ronald, Shaffer Eldon, Pfannkuche Hans-Juergen, Earnest David
Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, AB, 2N 4N1, Canada.
Lipids Health Dis. 2006 Jun 22;5:15. doi: 10.1186/1476-511X-5-15.
Tegaserod is effective in treating IBS patients with constipation, and does not alter gallbladder motility in healthy individuals or in patients with IBS. However, it is not known if tegaserod affects the biliary tract in gallstone disease, so to this end the effects of tegaserod on bile composition and hepatic secretion of Richardson ground squirrels maintained on an enriched cholesterol diet were examined.
Animals were fed either a control (0.03%) or enriched (1%) cholesterol diet for 28 days, and treated s.c. with tegaserod (0.1 mg/kg BID) or vehicle. Bile flow, bile acid, phospholipids and cholesterol secretion were measured with standard methods. Tegaserod treatment or enriched cholesterol diet, alone or combination, did not alter body or liver weights. The enriched cholesterol diet increased cholesterol saturation index (CSI), cholesterol concentrations in gallbladder and hepatic duct bile by approximately 50% and decreased bile acids in gallbladder bile by 17%. Tegaserod treatment reversed these cholesterol-induced changes. None of the treatments, drug or diet, altered fasting gallbladder volume, bile flow and bile salts or phospholipid secretion in normal diet and cholesterol-fed animals. However, tegaserod treatment prevented the decreases in bile acid pool size and cycling frequency caused by the enriched cholesterol diet, consequent to re-establishing normal bile acid to concentrations in the gall bladder. Tegaserod had no effect on these parameters with normal diet animals.
Tegaserod treatment results in increased enterohepatic cycling and lowers cholesterol saturation in the bile of cholesterol-fed animals. These effects would decrease conditions favorable to cholesterol gallstone formation.
替加色罗对治疗便秘型肠易激综合征患者有效，且对健康个体或肠易激综合征患者的胆囊运动无影响。然而，尚不清楚替加色罗是否会影响胆结石疾病患者的胆道，因此为此研究了替加色罗对喂食高胆固醇饮食的理查森地松鼠胆汁成分和肝脏分泌的影响。
动物喂食对照（0.03%）或高胆固醇（1%）饮食28天，并皮下注射替加色罗（0.1mg/kg，每日两次）或赋形剂。采用标准方法测量胆汁流量、胆汁酸、磷脂和胆固醇分泌。单独或联合使用替加色罗治疗或高胆固醇饮食均未改变体重或肝脏重量。高胆固醇饮食使胆固醇饱和指数（CSI）、胆囊和肝管胆汁中的胆固醇浓度增加约50%，并使胆囊胆汁中的胆汁酸减少17%。替加色罗治疗逆转了这些由胆固醇引起的变化。在正常饮食和喂食胆固醇的动物中，无论是药物还是饮食治疗，均未改变空腹胆囊体积、胆汁流量以及胆汁盐或磷脂分泌。然而，替加色罗治疗可防止高胆固醇饮食导致的胆汁酸池大小和循环频率降低，并因此重新建立胆囊中正常的胆汁酸浓度。替加色罗对正常饮食动物的这些参数无影响。
替加色罗治疗可增加肠肝循环，并降低喂食胆固醇动物胆汁中的胆固醇饱和度。这些作用将减少有利于胆固醇胆结石形成的条件。
