急性血糖波动对肝细胞凋亡的影响及可能的机制研究

目的探讨急性血糖波动对肝细胞凋亡的影响及可能的机制。方法选择30只健康雄性Wistar大鼠，将其随机分为3组：对照组、血糖波动组及持续性高血糖组，各10只。以间断和持续静脉滴注50％葡萄糖注射液48h的方法，建立急性血糖波动和持续性高血糖雄性Wistar大鼠动物模型。滴注48h后，采用比色法检测大鼠血清丙二醛（MDA）水平及超氧化物歧化酶（SOD）活性；采用Tunnel方法检测肝细胞凋亡的情况；采用免疫组化方法检测肝细胞内核因子-KB（NF—KB）、Jun氨基末端激酶-1（JNK1）表达。结果血糖波动组大鼠MDA水平、SOD活性及MDA／SOD与对照组、持续性高血糖组比较，差异有统计学意义（P〈0．05）；血糖波动组大鼠肝细胞凋亡率显著高于对照组及持续性高血糖组，差异亦有统计学意义（P〈0．05）。血糖波动组大鼠肝细胞内NF—KB、JNK1表达水平及JNK1／NF—KB值亦显著高于对照组及持续性高血糖组（P〈0．05）。结论血糖波动能诱导氧化应激增强，进而使JNK1、NF—KB细胞信号转导途径激活，这可能是导致肝细胞凋亡的主要原因。

Acute Blood Glucose Fluctuation Has Effects on the Hepatocyte Apoptosis

Objective To investigate that acute blood glucose fluctuation has the effect on the hepatocyte apoptosis.Methods The male Wistar rats were infused intermittently or consistently with 50% glucose solution.The level of maleic dialdehyde(MDA) and superoxide dismutase(SOD) was mearused with colorimetry.The expression of hepatocyte apoptosis was determined with the tunnel method.Results The levels of serum MDA and SOD of fluctuative blood glucose group and the ratio of MDA to SOD were significantly higher than consistently high blood glucose group(P＜0.01).The expression of the hepatocyte apoptosis in fluctuative blood glucose group was also evidently higher than that of consistently high blood glucose group and control group(P＜0.05).The expression of nuclear factorκB (NF-κB)and N-terminal Kinase-1(JNK1) in blood glucose fluctuation group is evidently higher than consistently high blood glucose group and control group(P＜0.01).Conclusion The hepatocyte apoptosis were increased by the oxidative stress induced by acute blood glucose fluctuation.Blood glucose fluctuation would increase oxidative stress in hepatocytes,which could result in the unbalance of the expression of NF-κB and JNK1 that would cause hepatocyte apoptosis.