论文部分内容阅读
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(P<0.05)。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),P<0.05]及JNK下降[(0.38±0.01)vs(0.21±0.01)vs(0.12±0.02),P<0.05]。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。
Objective To observe the effect of liraglutide on the expression of endoplasmic reticulum stress-regulated protein (GRP78) and c-Jun N-terminal kinase (JNK) and lipid deposition in liver of high fat diet rats. Methods The IR rat model was established by feeding with high-fat diet. The rats were randomly divided into control group (Con), high fat group (HFD), low dose liraglutide group (LL) and high dose liraglutide group (HL). Two weeks after drug intervention, five rats in each group were randomly assigned to a high-insulin-plus-glucose clamp test. Results Compared with HFD and LL group, the content of TG (~ L TG) in HL group decreased (P <0.05). Western blot results showed that compared with HFD and LL group, GRP78 [(1.24 ± 0.13) vs (0.97 ± 0.04) vs (0.62 ± 0.17), P <0.05, and JNK decreased significantly in HL group [(0.38 ± 0.01) vs ± 0.01) vs (0.12 ± 0.02), P <0.05]. Electron microscopy results showed that a large number of lipids were found in the hepatocytes of HFD group, and the rough endoplasmic reticulum was obviously expanded and degranulation was obvious. In the HL group, there was no lipid accumulation in the hepatocytes, and the expansion of rough endoplasmic reticulum and degranulation were significant ease. Correlation analysis showed that the expressions of GRP78 and JNK were positively correlated with FFA and LTG, and negatively correlated with glucose infusion rate (GIR). Conclusion Liraglutide can ameliorate lipid metabolism and liver lipid deposition in rats with high fat diet in a concentration-dependent manner and reduce IR. The mechanism may be related to the depression of GRP78 / JNK pathway in liver.