CAJ | 학술논문

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、GRP78 mRNA 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。
목적：연구내질망응격재고지음식소치간손상중적작용급기궤제。방법48지강단유웅성 SD 대서,수궤분위고지조화대조조。분별채용고지사료화보통사료위양,재제8、12、16주말측량체질량、내장지방질량급간장질량；검측혈청간공능；HE 염색관찰간장병리변화；투사전경관찰간장내질망정황；RT-PCR 법검측량조대서간세포내활화전록인자6(ATF6)、당조절단백78(GRP78)mRNA 적표체。결과①고지조대서체질량화내장지방질량명현고우대조조(P <0.05)。②고지조곡병전안매(ALT)급곡초전안매(AST)균수시간연장경도승고(P >0.05),ALT 재제16주여대조조유현저차별(P <0.05)。③HE 염색광경하가견고지조재제8주간내출현소포성지방변성,12~16주시,간장지방변성진일보가중。④전경하가견,8주시,고지조대서간세포내취집대량지적,결구기본청석,조면내질망결구기본정상；12주급16주,세포내지적증가,조면내질망지내가견선양결구침적。⑤고지조대서간조직내ATF6、GRP78 mRNA 재각개시간점균현저고우대조조(P <0.05)。결론유년고지음식가인기내장지방취집、간세포지방변성급간공손상。고지음식유도간손상적궤제가능여 ATF6개도적내질망응격밀절상관。
Objective To study the effects of endoplasmic reticulum stress on liver damage in young rats fed with high-fat diet.Methods We divided 48 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 1 6 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 week 1 6 was increased significantly compared with that in controls (P < 0.05 ).③ Liver cells in high-fat diet group had steatosis at week 8 and the steatosis became more serious between week 12 and week 1 6.④ In 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 week 1 6,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 1 6 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.