小牛血去蛋白提取物调节急性缺氧模型小鼠肝能量代谢及其作用靶点的研究

目的：考察小牛血去蛋白提取物（DECB）在急性缺氧条件下对小鼠耐缺氧的作用，并初步探索其调节肝脏中能量代谢的可能机制。方法：构建急性缺氧小鼠模型，考察空白组（CON）、模型组（MOD），模型给药组（MOD+DECB）小鼠耐缺氧时间，并检测小鼠肝脏、血清中糖、乳酸、ATP、酮体、三酰甘油（TG）及总胆固醇（TC）的含量，采用mRNA芯片筛选DECB处理后小鼠肝脏中差异表达基因，并进行聚类分析及Real time PCR验证。结果：MOD+DECB组小鼠耐缺氧时间明显高于MOD组，差异具有显著性（P<0.05）；MOD+DECB组血清中糖、乳酸含量显著低于MOD组，酮体含量显著高于MOD组，MOD+DECB组肝脏中糖、ATP和酮体的含量显著高于MOD组，乳酸含量显著低于MOD组，差异具有显著性（P<0.01）。肝脏和血清中TG及TC含量各组之间无显著差异。mRNA表达谱芯片分析共筛选出1 186个差异表达基因，其中上调表达基因495个，占基因总数的41.7%，下调表达基因691个，占基因总数的58.3%，其中Hmgcs2、Cpt1a、Angptl4、Cyp8b1、Ehhadh基因参与小鼠机体能量代谢密切相关，Real time PCR验证结果与芯片分析结果一致。结论：DECB可通过调控Hmgcs2、Cpt1a、Angptl4、Cyp8b1、Ehhadh基因的表达，调节肝脏中能量的代谢，从而提高小鼠耐缺氧的能力。

Effects of deproteinized extract of calf blood on the energy metabolism of liver in acute hypoxia model mice and its targets

OBJECTIVE To investigate the effect of deproteinized extract of calf blood (DECB) on the energy metabolism of liver in acute hypoxia model mice and to explore the possible mechanism of its regulation of energy metabolism. METHODS Acute hypoxia model was established in mice. The duration of hypoxia tolerance of mice in normal control group (CON), acute hypoxia model group(MOD), administration group(MOD+DECB) was observed. The contents of glucose, lactic acid, ATP, ketone body, triglyceride (TG) and total cholesterol (TC) in liver and serum of mice were detected. The differentially expressed genes in DECB treated mice liver were screened by mRNA microarray, and then cluster analysis and Real time PCR validation were performed. RESULTS The hypoxia tolerance time of mice in the MOD+DECB group was significantly prolonged compared with that MOD group (P<0.05). Compared with those in MOD group, glucose and lactic acid contents reduced and the ketone body contents increased significantly in the serum of MOD+DECB group. Compared with those in the MOD group, glucose, ATP, ketone body contents increased and actic acid contents decreased significantly in the liver of MOD+DECB group (P<0.01). There was no significant difference in the contents of TG and TC in liver and serum among groups. The mRNA expression chip screening results showed that 1186 differentially expressed genes were screened, among which 495 genes were up-regulated, accounting for 41.7% of the total number of genes, and 691 were down-regulated, accounting for 58.3% of the total number of genes. In these genes, Hmgcs2, Cpt1a, Angptl4, Cyp8b1 and Ehhadh genes were involved in the energy metabolism in mice, and mainly closely related to some biological processes, including ABC transporters, adipocytokine signaling pathway and PPAR signaling pathway. The results of real-time PCR were consistent with the gene-chip findings. CONCLUSION The DECB can effectively regulate the energy metabolism in the liver and improve the ability of hypoxia tolerance in mice by promoting gene expression of Hmgcs2, Cpt1a, Angptl4, Cyp8b1 and Ehhadh genes.