新型生长抑素类似物SOM230减轻胆总管结扎大鼠肝纤维化  

Suppressive effect of low-dose SOM230 on bile duct ligation induced liver fibrosis in rats

作　　者：吴鹏[1] 杨爱婷[1] 范旭[1] 佟小非[1] 尤红[1] 

机构地区：[1]首都医科大学附属北京友谊医院肝病中心,100050

出　　处：《肝脏》2011年第6期457-460,共4页Chinese Hepatology

基　　金：国家"十一五"科技重大专项(2009ZX10005-061)

摘　　要：目的应用胆总管结扎大鼠肝纤维化模型,观察长效生长抑素类似物SOM230对胆管结扎所致大鼠肝纤维化的治疗作用。方法雄性SD大鼠80只,随机分为模型组、高剂量预防组(80mg/kg SOM230)、低剂量预防组(8 mg/kg SOM230)、假手术组及正常对照组。分别在术后第2周和第4周取心脏血及肝组织,观察肝组织学变化,检测肝组织羟脯氨酸水平和血清肝功能指标。结果在低剂量组,HE染色显示不同时间点低剂量SOM230组胆管增生程度较模型组轻,Masson染色也显示低剂量组较模型组胶原沉积量少。对肝纤维化情况半定量评分结果显示,2周时(1.5±0.5比2.1±0.4,P<0.0.5)和4周时(2.5±0.3比3.2±0.3,P<0.05)评分均低于模型组。羟脯氨酸含量测定结果与上述结果一致,术后2周(112.5±21.5)μg/g比167.8±23.4μg/g,P<0.05]和4周时[(131.6±47.3)μg/g比(215.3±57.5)μg/g,P<0.05]低剂量组明显低于模型组,但高剂量组S0M230并没有明显改善纤维化积分和羟脯氨酸的作用,可能与高剂量导致的γ-GT、AP和TBil升高有关。两个剂量对肝功能和胆汁淤积情况没有明确改善,对白蛋白均没有明显作用。结论低剂量SOM230虽然对肝功能没有明显的改善作用,但可显著抑制胶原合成。Objective To investigate the effect of long-acting somatostatin analog SOM230 in rat models of bile duct ligation-induced liver fibrosis.Methods Eighty male Spratue-Dawley rats were randomly divided into five groups as follows：bile duct ligation,high dose SOM230（80mg/Kg）,low dose SOM230（8 mg/kg）.sham operation and normal control.Biochemical markers in serum,hydroxyproline and histology were determined on 2 weeks and 4 weeks after operation,respectively.Results In histopathological examination,low dose of SOM230 improved bile duct proliferation and collagen deposition,which could be demonstrated by semiquantitative grades of liver fibrosis.At 2 weeks（1.50±0.45 vs.2.08±0.38） and 4 weeks（2.5±0.32 uv.3.17±0.26） after operation,grade in low dose group was lower compared with model group.Low dose of SOM230 decreased the level of hydroxyproline compared with model group at 2 weeks（112.5±21.5 vs.167.8±23.4）evidently.High dose of SOM230 did not improve fibrosis which may be associated with the induction of high y-GT,ALP and TB by high dose of SOM230.Neither high dose nor lowdose of SOM230 could significantly improve the liver function and cholestasis,and affect the serum albumin.Conclusion Low dose of SOM230 can reduce collagen deposition in the liver,but neither high dose SOM230 nor low dose SOM230 injected subcutaneously improve liver function.

关 键 词：生长抑素类似物SOM230 肝纤维化 胆总管结扎 

分 类 号：R575.2[医药卫生—消化系统]