A BASIC APPROACH TO ASSOCIATION OF INSULIN RESISTANCE WITH TNF α IN COWS WITH FATTY LIVER

最近有报道称，在围产期期间有时观察到具有胰岛素抗性的奶牛，并且它们的产奶量显著降低。指出脂肪肝与其发病机制密切相关。脂肪细胞分泌的肿瘤坏死因子α（TNFα）被认为是胰岛素抵抗的最重要因素。我们设计了两个诱导脂肪肝的实验。试验一，奶牛禁食4天，使能量处于负平衡状态。此外，作为实验-2，奶牛被给予乙硫氨酸，类似于蛋氨酸的物质，以减少肝脏中蛋白质的产生。在每个试验中分析所用奶牛的胰岛素抵抗和TNF α。禁食后肝脏甘油三酯（TG）含量明显升高.在脂肪肝的发生发展过程中，胰岛素抵抗程度增加.禁食奶牛血清TNFα浓度无显著变化.在肝脏的显微形态学分析中，与对照组相比，脂肪肝奶牛的肝基底层显著变厚。乙硫氨酸处理组奶牛肝脏TG含量显著升高.血清载脂蛋白B-100浓度在脂肪肝发生发展过程中显著降低.肝硬化明显诱导胰岛素抵抗.在处理的奶牛中观察到高血糖和高胰岛素血症。结果表明，两种实验方法均能有效诱导大鼠脂肪肝的发生。虽然对肝组织中TNFα进行了生化和组织学分析，但未检测到其与肝硬化的相关性。我们正计划改进TNFα测定和组织学标本以仔细检查这些实验。

It has been recently reported that cows with insulin resistance are sometime observed during the periparturient period, and their milk production are remarkably decreased. It is pointed out that fatty liver is closely linked to that pathogenesis. Tumor necrosis factor ct (TNFα) secreted from fatty cell is considered to be the most important factor in the insulin resistance. We designed two experiments for induction of fatty liver. In experiment-1, cows were fasted for 4 day to be fallen into negative energy balance. Moreover, as experiment-2, cows were administrated ethionine, analogous substance of methionine, to reduce the production of proteins in the liver. Insulin resistance and TNF α of used cows were analyzed in each experiment.Experiment-11. Liver triglyceride (TG) content was apparently increased after fasting.2. The increase of insulin resistance was observed in the development of fatty liver.3. Serum concentration of TNFα was not significantly changed in the fasted cow.4. In micromorphological analysis of liver, hepatic basal lamina in the cow with fatty liver remarkably became thicker compared to that in control.Experiment-21. Liver TG contents were remarkably increased in ethionine-treated cows.2. Serum concentration of apolipoprotein B-100 was significantly decreased in the development of fatty liver.3. Hepatic lipidosis apparently induced insulin resistance.4. Hyperglycemia and hyperinsulinism were observed in treated cows.5. The apparent association of fatty liver with serum concentration of TNFα was not detected.From these results, two experiments were suggested to be effective for induction of fatty liver. Although TNFα of sampled liver tissues were analyzed biochemically and histologically, its relevance to hepatic lipidosis was not detected. We are planning to improve TNFα determination and histological specimens to scrutinize these experiments.