摘要
目的:探讨生长抑素(SST)及其类似物奥曲肽(OCT)对大鼠肝细胞的保护作用及其机制。方法:以原代培养肝细胞建立无水乙醇/四氯化碳(CCl4)细胞损伤模型,观察SST及OCT预处理对培养上清液中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)含量的影响。此外,将75只SD大鼠随机分为正常对照组、肝纤维化模型组及大、中、小剂量SST治疗组。除正常对照组外均以40%CCl4皮下注射8周,期间各SST治疗组分别给予SST200μg·kg-1·d-1、100μg·kg-1·d-1、50μg·kg-1·d-1。采用酶试剂法、末端核苷酸转移酶介导的脱氧三磷酸尿苷原位缺口末端标记法(TUNEL)分别检测肝功能及肝细胞凋亡指数。结果:经SST(10-8-10-6mol/L)及OCT(10-7-10-5mol/L)预处理后,损伤模型组肝细胞的培养上清液中ALT、AST水平显著下降。不同剂量SST治疗还能明显降低肝纤维化大鼠的血清ALT、AST、碱性磷酸酶(ALP)及总胆红素(TBIL)水平,提高血清清蛋白(ALB)水平,抑制肝细胞凋亡,其中小剂量SST治疗组最佳。结论:SST及OCT可减轻CCl4引起的肝细胞损伤,改善肝功能,并抑制肝细胞凋亡,可能在肝纤维化的防治中发挥重要作用。
AIM- To investigate the protective effect of somatostatin （SST） and octreotide （OCT） on rat hepatocytes. METHODS： The primary hepatocytes were pretreated with different concentrations of SST and OCT. The levels of alanine minotransferase （ALT） and aspartate aminotransferase （AST） in culture supernatant were analyzed by the model of ethanol/carbon tetrachloride （ CCl4 ） - induced hepatocyte injury. Additionally, 75 Sprague - Dawley rats were divided into 5 groups at random, including normal control, model control, SST - treated model groups at high, medium and low doses （200 μg · kg^-1 · d^-1 , 100 μg ·kg^-1 · d^-1 and 50 μg · kg^-1 · d^-1 , respectively）. Except for the normal controls, all rats were injected with 40% CC14 subcutaneously for 8 weeks to establish hepatic fibrosis. Meanwhile, rats of SST - treated model groups were given at different doses of SST twice a day in the same way. Thereafter, the liver function and apoptosis index of hepatocytes were detected by standard enzyme method, terminal deoxynucleotidyl transferase - mediated dUTP nick end labeling （TUNEL）, respectively..RESULTS： Compared with those of injury model group, the hepatocytes pretreated with SST （ 10 ^-8- 10 ^-6 mol/L） and OCT （ 10 ^-7 - 10^ -5 mol/L） exhibited significantly decreased levels of ALT and AST in the culture supernatant. Furthermore, most indices of liver function including ALT, AST, alkaline phosphatase （ ALP）, total bilirubin （TBIL） and albumin （ALB） improved obviously in all SST- treated groups, especially in the group treated with low dose of SST. The apoptosis index of hepatocytes in the fibrotic liver was also reduced greatly by the treatment with low dose of SST. CONCLUSION： SST and OCT may protect hepatocytes against CC14 - induced injury, inhibit hepatocyte apoptosis, and improve the liver function. These findings suggest them a potential efficiency in the prevention of hepatic fibrosis.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2008年第4期730-733,共4页
Chinese Journal of Pathophysiology
基金
上海市科委基金资助项目(No004119047)
关键词
生长抑素
奥曲肽
肝细胞
肝硬化
Somatostatin
Octreotide
Hepatocytes
Liver cirrhosis
