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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 study the changes of protein phosphatase1 (PP1) and protein phosphatase 2A (PP2A) in fatty liver induced by high fat diet and the intervention of curcumin. Methods: The fatty liver model induced by simple high fat diet was randomly divided into normal group, model group and curcumin group. The model was made for 14 weeks. Curcumin group was administrated with curcumin for 6 weeks from the 9th week. Observation items: (1) Hepatic tissue was stained with hematoxylin and eosin (HE) to observe the degree of hepatic steatosis in each group; (2) The content of triglyceride (TG), free fatty acid (FFA), PP1, 3) The levels of PP1, PP2A mRNA in liver tissue; (4) The changes of fasting insulin (FINS), fasting blood glucose (FBG) and insulin resistance index (HOMA- PP2A content and serum FINS, FBG, HOMA-IR correlation analysis. Results: (1) Hepatic steatosis and vacuolar degeneration were observed in the model group. The content of FINS, FBG, HOMA-IR and TG, FFA, PP1 and PP2A in the liver tissue of the model group were significantly increased (P <0.01) , And the levels of PP1 and PP2A mRNA in liver tissue were also significantly increased (P <0.01). The levels of FINS, FBG, HOMA-IR and TG, FFA, PP1 and PP2A in the curcumin group were significantly lower than those in the untreated group (P <0.01), and the levels of PP1 and PP2A mRNA in the liver tissue were significantly lower than those in the model group Significantly lower (P <0.01). (2) There was a significant positive correlation between the content of PP1 and PP2A in liver tissue and the content of TG and FFA in liver tissue, and also positively correlated with the levels of FINS, FBG and HOMA-IR. Conclusion: (1) The content and mRNA level of PP1, PP2A in liver tissue of fatty liver rats are significantly increased, which is of great significance in the pathological mechanism of fatty liver. (2) Curcumin can significantly reduce the content and mRNA level of PP1, PP2A in fatty liver rats, which may be the important mechanism of the drug in preventing and treating fatty liver.