Effects of AG490 on lipid metabolism of the obese mouse and _expression of related genes | AG490对肥胖模型小鼠脂代谢及相关基因表达的影响

Chinese. 研究AG490阻断肥胖模型小鼠JAK2/STAT3信号通路对脂代谢及相关基因表达的影响。以雄性昆明小鼠为供试动物，构建肥胖模型。将肥胖模型小鼠分为2组，处理组用JAK2特异性抑制剂AG490(1 mg/(kg•d))腹腔连续注射2周，对照组腹腔连续注射相同剂量的生理盐水。2周后处死小鼠，检测各组小鼠血清中总胆固醇（TC）、总甘油三酯（TG）、高密度脂蛋白固醇（HDL-C）的含量；取脂肪组织提取总RNA，RT-PCR方法检测JAK2/STAT3信号通路基因（JAK2、STAT-3）及脂代谢关键基因（FAS、PPARγ、HSL）的表达量。与对照组相比，AG490可显著降低小鼠血清中的HDL-C水平；与对照组相比，处理组脂肪组织中JAK-2 mRNA表达量差异不显著（P＞0.05），STAT3 mRNA表达量显著降低（P＜0.05），脂代谢相关基因FAS mRNA表达量极显著降低（P＜0.01），PPARγ mRNA表达量显著降低（P＜0.05），HSL mRNA表达量差异不显著（P＞0.05）。JAK2/STAT3通路可能通过影响脂肪组织中生脂基因的表达而调节体脂沉积。

English. It aimed to study the effects of AG 490 on lipid deposition and expression of relevant genes of the obese mouse by JAK2/STAT3 signal transduction pathway occlusion. The obese model which was constructed by the male Kunming mouse were divided into 2 groups. The treatment group was treated with intraperitoneal injection by AG490 (1 mg/(kg•d)) and the control group was treated by the same method with NS (1 mg/(kg•d)) for two weeks, then executed and the adipose was reserved. To estimate the content of TC, TG and HDL-C in blood, Total RNA was extracted. RT-PCR was used to analyze the expression of JAK2/STAT3 signal transduction pathway and adipogenesis genes (FAS, PPARγand HSL). Compared with the control group, AG490 was able to cut down the level of HDL-C significantly in blood with the treated mice; Compared with the control group, the mRNA expression of JAK2 had not significant difference (P＞0.05) and the mRNA expression of STAT3 was significantly lowered (P＜0.05) in the treatment group. The mRNA expression of FAS was significantly lower (P＜0.01), the mRNA expression of PPARγ had a significant reduction (P＜0.05) and the mRNA expression of HSL had no significant difference (P＞0.05). We conjectured that JAK2/STAT3 signal transduction pathway regulated lipid deposition by affecting the expression of adipogenesis genes in adipose tissue.