奥氮平对小鼠白色脂肪米色化的抑制作用及其机制

发布时间：2018-11-01 15:47

【摘要】：从奥氮平(olanzapine,OLA)对白色脂肪米色化(beiging)的调节作用探讨其引起代谢紊乱的可能机制。C57BL6/J小鼠连续28 d灌胃给予高、低剂量(4,8 mg/kg)OLA,隔天记录体重及摄食变化;通过糖耐量实验和冷应激考察小鼠血糖调控和产热能力的变化。分离小鼠肾周(pWAT)、附睾(eWAT)及腹股沟(iWAT)处白色脂肪,通过解偶联蛋白-1(UCP-1)免疫组化技术和苏木精-伊红染色确证米色化程度的改变;通过Western blot考察奥氮平对米色脂肪分化关键调控蛋白哺乳动物雷帕霉素靶蛋白(mTOR)活化和Notch1胞内结构士或(N1ICD)表达的影响。实验结果表明:OLA可致小鼠基础产热明显降低,并可抑制环境适应性产热和葡萄糖利用。OLA引起腹股沟处米色脂肪分化异常,抑制冷应激诱导的白色脂肪米色化及UCP-1激活,并显著上调磷酸化mTOR(p-mTOR)与N1ICD的表达。以上结果提示,白色脂肪米色化的抑制作用参与到OLA诱导的代谢紊乱,mTOR-Notch信号通路的激活可能是其中的关键分子事件。
[Abstract]:To explore the possible mechanism of metabolism disorder induced by olanzapine (olanzapine,OLA) on (beiging) of white fat beige. C57BL6/J mice were given high and low dose (4 ~ 8 mg/kg) OLA, by intragastric administration for 28 days. Body weight and food intake were recorded the next day; Glucose tolerance test and cold stress were used to investigate the changes of blood glucose regulation and heat production ability in mice. White fat was isolated from the epididymal (eWAT) and inguinal (iWAT) of (pWAT), of mice around the kidney. The changes of the degree of beige color were confirmed by immunohistochemical technique of uncoupling protein-1 (UCP-1) and hematoxylin eosin staining. The effects of olanzapine on the activation of rapamycin target protein (mTOR) and the expression of Notch1 intracellular structure or (N1ICD) were investigated by Western blot. The results showed that OLA could significantly decrease the basic heat production and inhibit the environmental adaptive heat production and glucose utilization. OLA induced abnormal beige fat differentiation in the groin, and inhibited the white fat beige and UCP-1 activation induced by cold stress. The expression of phosphorylated mTOR (p-mTOR) and N1ICD was significantly up-regulated. These results suggest that the inhibition of white aliphatic decolorization is involved in the metabolic disorder induced by OLA, and the activation of mTOR-Notch signaling pathway may be a key molecular event.
【作者单位】：东南大学附属中大医院药学部;南京中医药大学附属医院药学部;
【基金】：江苏省自然科学基金资助项目(No.BK20150644,No.BK20141035)~~
【分类号】：R965

【相似文献】