目的研究内质网应激在高脂饮食所致肝损伤中的作用及其机制。方法 48只刚断乳雄性SD大鼠,随机分为高脂组和对照组。分别采用高脂饲料和普通饲料喂养,在第8、12、16周末测量体质量、内脏脂肪质量及肝脏质量;检测血清肝功能;HE染色观察肝脏病理变化;透射电镜观察肝脏内质网情况;RT-PCR法检测两组大鼠肝细胞内活化转录因子6(ATF6)、糖调节蛋白78(GRP78)mRNA的表达。结果 1高脂组大鼠体质量和内脏脂肪质量明显高于对照组(P〈0.05)。2高脂组谷丙转氨酶(ALT)及谷草转氨酶(AST)均随时间延长轻度升高(P〉0.05),ALT在第16周与对照组有显著差别(P〈0.05)。3HE染色光镜下可见高脂组在第8周肝内出现小泡性脂肪变性,12-16周时,肝脏脂肪变性进一步加重。4电镜下可见,8周时,高脂组大鼠肝细胞内聚集大量脂滴,结构基本清晰,粗面内质网结构基本正常;12周及16周,细胞内脂滴增加,粗面内质网池内可见线样结构沉积。5高脂组大鼠肝组织内ATF6、GRP78mRNA在各个时间点均显著高于对照组(P〈0.05)。结论幼年高脂饮食可引起内脏脂肪聚集、肝细胞脂肪变性及肝功损伤。高脂饮食诱导肝损伤的机制可能与ATF6介导的内质网应激密切相关。
Objective To study the effects of endoplasmic reticulum stress on liver damage in young rats fed with high-fat diet.Methods We divided48 male weaned young rats randomly into high-fat diet group and control group,which were separately fed with high-fat diet and normal diet.After feeding 8,12 and 16 weeks,the body weight and visceral fat of the rats were measured.The serum liver function was measured.The morphology of livers was observed by HE and transmission electron microscopy.The mRNA expressions of ATF6 and GRP78 in hepatocytes were measured with RT-PCR.Results 1 The body weight and visceral fat weight of rats in high-fat diet group increased compared with those in control group(P〈0.05).2 Alanine aminotransferase and aspartate aminotransferase in high-fat diet group increased slightly over time(P〉0.05);alanine aminotransferase at week16 was increased significantly compared with that in controls(P〈0.05).3 Liver cells in high-fat diet group had steatosis at week8 and the steatosis became more serious between week12 and week16.4In high-fat diet group at week 8 there were a large number of lipid droplets in the cytoplasm,and the cell structure was close to that of normal cells;rough endoplasmic reticulum was nearly normal and the ribosome was visible.At week 12 and week16,besides a large number of lipid droplets,we could also see that some substances with line-like structure deposited in rough endoplasmic reticulum pool.5 The expressions of ATF6 and GRP78 mRNA in hepatocytes in high-fat group at weeks 8,12 and 16 were significantly increased compared with those in control group(P〈0.05).Conclusion High-fat diet in infants can cause visceral fat accumulation,fatty degeneration of hepatocytes and liver injury.ATF6-mediated endoplasmic reticulum may be closely related to the liver injury which results from highfat diet.