蛋白磷酸酶1和蛋白磷酸酶2A在高脂饮食诱导的大鼠脂肪肝中的变化及姜黄素的干预作用

Changes of Protein Phosphatase1 and Protein Phosphatase 2A in Fatty Liver in Rats Induced by High-fat Diet and Curcumin Intervention

目的:研究蛋白磷酸酶1(Protein phosphatase1,PP1)及蛋白磷酸酶2A(Protein phosphatase 2A,PP2A)在高脂饮食诱导的大鼠脂肪肝中的变化及姜黄素的干预作用。方法:采用单纯高脂饮食诱导的大鼠脂肪肝模型,随机分正常组、模型组和姜黄素组。造模14周,其中姜黄素组在第9周起予以姜黄素灌胃干预6周。观察项目:(1)肝组织HE染色,观察各组肝脂肪变性程度变化;(2)肝组织甘油三酯(triglyceride,TG)、游离脂肪酸(free fatty acid,FFA)、PP1、PP2A含量;(3)肝组织PP1、PP2A mRNA水平;(4)血清空腹胰岛素(FINS)含量、空腹血糖(FBG)含量及胰岛素抵抗指数(HOMA-IR)的变化;(5)肝组织TG、FFA、PP1、PP2A含量及血清FINS、FBG、HOMA-IR的相关性分析。结果:(1)模型组肝组织出现显著的肝细胞脂肪变性及空泡样变,血清FINS、FBG含量、HOMA-IR和肝组织TG、FFA、PP1、PP2A含量显著升高(P<0.01),肝组织PP1、PP2A mRNA水平亦显著升高(P<0.01)。姜黄素组的上述病理改变明显减轻,血清FINS、FBG含量、HOMA-IR和肝组织TG、FFA、PP1、PP2A含量较模型组显著降低(P<0.01),肝组织PP1、PP2A mRNA较模型组显著降低(P<0.01)。(2)肝组织PP1、PP2A含量与肝组织TG、FFA含量呈显著正相关,与血清FINS、FBG含量、HOMA-IR亦呈显著正相关。结论:(1)脂肪肝大鼠的肝组织PP1、PP2A含量和mRNA水平显著升高,在脂肪肝病理机制中有重要意义。(2)姜黄素可显著降低脂肪肝大鼠的PP1、PP2A含量和mRNA水平,这可能为该药防治脂肪肝作用的重要机制。

Objective ： To investigate the changes of protein phosphatase 1 and protein phosphatase 2A in fatty liver in rats induced by high - fat diet and the curcumin intervention effect. Methods ： Non - alcoholic fatty liver disease in SD male rats were induced by high - fat diet for 14 weeks. At the begaining of the ninth week, the rats were divided into model and curcumin groups at random, and were given a gavage for six weeks. The observing items ： （ 1） hepatic steatosis （ H. E. staining） ; （2） hepatic triglyceride （TG）, free fatty acid （ FFA）, protein phosphatasel （ PP1 ） and protein phosphatase 2A （PP2A） ; （ 3 ） hepatic PP1 and PP2A mRNA level ; （4） changes of serum fasting insulin （ FINS）, fasting plasma glucose（FBG） and insulin resistance index （HOMA- IR）;（5 ）correlation analysis among serum FINS, FBG, HOMA - IR,hepatic TG, FFA and PP1, PP2A. Results ： （ 1 ） Significant hepatic steatosis and vesicle changes were observed in model group. The serum FINS, FBG, HOMA - IR and hepatic TG, FFA, PP1 and PP2A contents of model group were significantly higher than that of normal group （P 〈 0.0/）, hepatic PP1 and PP2A mRNA levels of model group were higher than that of normal group too （ P 〈 0.01 ）. Hepatic pathological changes in the curcumin group were meliorated. The serum FINS, FBG, HOMA - IR and hepatic TG, FFA, PP1 and PP2A contents of curcumin group were significantly lower than that of model group（P 〈0.01 ）. The hepatic PP1 and PP2A mRNA level of cnrcumin group were significantly lower than that of model group （P 〈 0.01 ）. （2） Significant positive correlation was observed between hepatic TG, FFA and hepatic PP1, PP2A （P 〈 0.01 ）. The significant positive correlation was also observed between hepatic PP1, PP2A and serum FINS, FBG, HOMA - IR. Conclusion ： （ 1 ） Hepatic PP! and PP2A contents and mRNA level significantly increased in fatty liver in rats and play very important roles in pathological mechanisms of fatty liver disease. （2） Curcumin can decrease the hepatic PP1, PP2A contents and mRNA level which is the important mechanism of its prevention and treatment effect on fatty liver disease.