利拉鲁肽对高脂喂养大鼠肝脏内质网应激及脂质沉积影响的实验研究

发布时间：2018-03-18 13:42

本文选题：利拉鲁肽　切入点：胰岛素抵抗　出处：《中国糖尿病杂志》2017年01期 　论文类型：期刊论文

【摘要】：目的观察利拉鲁肽对高脂喂养大鼠内质网应激标记蛋白葡萄糖调节蛋白(GRP78)及c-Jun氨基端激酶(JNK)蛋白的表达及肝脏脂质沉积的影响。方法以高脂饮食喂养方法建立IR大鼠模型,成模后随机分为对照组(Con)、高脂组(HFD)、低剂量利拉鲁肽组(LL)、高剂量利拉鲁肽组(HL)。药物干预2周后,每组随机取5只行高胰岛素-正葡萄糖钳夹实验。结果与HFD和LL组比较,HL组肝脏内TG(~L TG)降低(P0.05)。Western blot结果显示,与HFD和LL组比较,HL组GRP78[(1.24±0.13)vs(0.97±0.04)vs(0.62±0.17),P0.05]及JNK下降[(0.38±0.01)vs(0.21±0.01)vs(0.12±0.02),P0.05]。电镜结果显示,HFD组肝细胞内有大量脂质,粗面内质网明显扩张,脱颗粒现象明显;HL组肝细胞内无脂质蓄积存在,粗面内质网扩张及脱颗粒现象得到显著缓解。相关分析结果显示,GRP78、JNK蛋白表达量与FFA、~LTG呈正相关,与葡萄糖输注率(GIR)呈负相关。结论利拉鲁肽可呈浓度依赖性改善高脂喂养大鼠脂代谢异常和肝脏脂质沉积,减轻IR,其作用机制可能与肝脏GRP78/JNK通路受抑有关。
[Abstract]:Objective to observe the effects of lilalutide on the expression of glucone-regulated protein GRP78 and c-Jun amino-terminal kinase (JNKK) protein in the endoplasmic reticulum (ER) stress marker and lipids deposition in the liver of rats fed with high fat diet. Methods IR rat model was established by high-fat diet. The model was randomly divided into three groups: control group (Concha), high fat group (HFDD), low dose riparutide group (LLX) and high dose riparutide group (HL1). Five rats in each group were randomly selected for hyperinsulin-glucose clamp test. Results compared with HFD and LL groups, the liver TG(~L in HL group decreased P0.05U. Western blot. Compared with HFD group and LL group, GRP78 (1.24 卤0.13vsl) 0.97 卤0.04 (0.62 卤0.17) and JNK (0.38 卤0.01) vs (0.21 卤0.01) vs 0.12 卤0.02 (P 0.05) were decreased in HL group. The results of electron microscope showed that there was a large amount of lipid in hepatocytes, the rough endoplasmic reticulum was dilated obviously, and there was no lipid accumulation in hepatocytes in HL group. The results of correlation analysis showed that the expression of GRP78 JNK protein was positively correlated with FFAA LTG. Conclusion Lilaru peptide can improve lipid metabolism abnormality and liver lipid deposition in a concentration-dependent manner in rats fed with high fat, and alleviate IR.Therefore, the mechanism may be related to the inhibition of liver GRP78/JNK pathway.
【作者单位】：承德医学院;承德医学院附属医院内分泌科;
【分类号】：R965

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