高脂联合地塞米松诱导小鼠急性脂肪肝模型的实验研究

发布时间：2018-04-23 02:40

本文选题：地塞米松 + 高糖高脂饲料　；参考：《重庆医学》2017年17期

【摘要】：目的研究地塞米松配高糖高脂饲料导致小鼠急性脂肪肝模型对药物剂量与时间依存性特征,优化药物性脂肪肝模型的条件。方法雄性昆明鼠分为对照组及高糖高脂饲料加腹腔注射地塞米松组,分3个时间点处死小鼠,检测小鼠体质量,肝质量,计算肝指数,检测血清及肝组织匀浆三酰甘油(TG),血清葡萄糖(GLU)含量,采用HE染色观察肝组织病理变化。肝组织提取总RNA反转录表达相关基因,肝组织提取总蛋白通过Westen Blot检测相关蛋白表达。结果与对照组比较,地塞米松模型组7d后,血及肝匀浆TG增高,肝指数增大,病理切片显示,脂肪肝形成。反转录PCR显示脂肪代谢相关基因表达有明显改变。Western Blot显示沉默信息调节因子1(SIRT1)明显下降。但是,随着地塞米松用量减少,时间延长,脂肪肝相关指标降低,脂代谢基因PPAR、FOXO3、FXR逐渐回升,LXR逐渐下降,蛋白SIRT1逐渐回升。结论高糖高脂饲料加地塞米松大剂量腹腔注射可以建立小鼠急性脂肪肝模型,并且模型的维持对地塞米松的剂量和用药时间有依存性,对于药物干预实验具有指导意义。
[Abstract]:Objective to study the dose-dependent and time-dependent characteristics of acute fatty liver model induced by dexamethasone and high glucose and high fat diet, and to optimize the condition of drug induced fatty liver model. Methods male Kunming rats were divided into control group and high-glucose high-fat diet plus dexamethasone group. The mice were killed at three time points. The body weight, liver mass and liver index were measured. Serum and liver homogenate triglyceride (TGG) and serum glucose glu (GLU) contents were detected and the pathological changes of liver tissue were observed by HE staining. Total RNA was extracted from liver tissue to express related genes, and total protein was extracted from liver tissue to detect the expression of related protein by Westen Blot. Results compared with the control group, after 7 days of dexamethasone model group, TG and liver homogenate increased, liver index increased, pathological section showed fatty liver formation. Reverse transcription PCR showed significant changes in the expression of genes related to fat metabolism. Western Blot showed that silencing signaling factor 1 (sirt1) was significantly decreased. However, with the decrease of dexamethasone dosage and the prolongation of time, the relative indexes of fatty liver decreased, the lipid metabolism gene PPAR- FOXO _ 3 FXR gradually increased and the protein SIRT1 gradually decreased. Conclusion High glucose and high fat diet plus high dose dexamethasone intraperitoneal injection can establish acute fatty liver model in mice, and the maintenance of the model is dependent on the dose of dexamethasone and the time of drug use, which has guiding significance for drug intervention experiment.
【作者单位】：三峡大学医学院肿瘤微环境与免疫治疗湖北省重点实验室;
【基金】：国家自然科学基金资助项目(81473461)
【分类号】：R-332;R575.5

【相似文献】