内质网应激在高脂饲料诱导幼年大鼠脂肪性肝损伤中的作用

发布时间：2018-06-02 11:23

本文选题：内质网应激 + 肝损伤　；参考：《西安交通大学学报(医学版)》2015年06期

【摘要】：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(P0.05)。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(P0.05),ALT在第16周与对照组有显著差别(P0.05)。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(P0.05)。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。
[Abstract]:Objective to study the role and mechanism of endoplasmic reticulum stress in liver injury induced by high fat diet. Methods 48 newly weaned male SD rats were randomly divided into hyperlipidemia group and control group. Body weight, visceral fat mass and liver mass were measured at the end of week 812, and liver function was detected by HE staining. Liver endoplasmic reticulum (ER) was observed by transmission electron microscopy (TEM) and RT-PCR was used to detect the expression of transcriptional factor 6 (ATF6) and glycosylregulatory protein (78(GRP78)mRNA) in rat hepatocytes. Results 1 the body weight and visceral fat mass in the hyperlipidemia group were significantly higher than those in the control group (P0.05n.2) and the alanine aminotransferase (alt) and glutamic oxaloacetic transaminase (AST) in hyperlipidemia group were significantly higher than those in the control group in the 16th week. Under the light microscope, the hyperlipidemia group appeared vesicular steatosis in the liver at the 8th week. Liver steatosis was further aggravated at 8 weeks under electron microscope. In high fat group, a large amount of lipid droplets were accumulated in liver cells, the structure was basically clear, the structure of rough endoplasmic reticulum was normal for 12 weeks and 16 weeks, and the lipid droplets in the cells increased. The level of ATF6mGRP78 mRNA in liver tissue of rats with high fat was significantly higher than that of control group (P 0.05) at each time point. Conclusion Juvenile high fat diet can induce the accumulation of visceral fat, fatty degeneration of hepatocytes and damage of liver function. The mechanism of liver injury induced by high fat diet may be closely related to endoplasmic reticulum stress mediated by ATF6.
【作者单位】：西安交通大学医学部第二附属医院儿科;西安市儿童医院;浙江大学附属儿童医院;
【基金】：国家自然科学基金资助项目(No.81172689) 西安交通大学医学部第二附属医院重大科研方向资助计划[No.YJ(ZDJH)2013(03)]~~
【分类号】：R575.5

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