Akt与Lpl在高脂饮食大鼠非酒精性脂肪肝形成中的作用

The role of Akt and Lpl in formation of nonalcoholic steatohepatitis in rat with a fat-rich diet

目的探讨丝氨酸/苏氨酸激酶(Akt)和脂蛋白脂酶(Lpl)在高脂饮食大鼠非酒精性脂肪肝(NASH)形成中的作用。方法40只雄性Wistar大鼠随机分为8周高脂模型组(n=10)、8周正常对照组(n=10)、12周高脂模型组(n=10)以及12周正常对照组(n=10),检测血脂、胆固醇、血糖、胰岛素,并计算胰岛素抵抗指数(IRI);病理学免疫组化检测Akt和Lpl在肝脏的表达;透射电镜观察肝脏的形态学改变。结果8周高脂模型组大鼠均个体肥胖,形成NASH,肝脏呈现体积增大、外形饱满圆钝、色泽灰黄、切面油腻、质地较脆等特点,并伴有高脂血症,以及肝细胞脂肪变性、肝小叶内炎症细胞浸润和肝细胞坏死;Akt和Lpl在肝脏表达明显减弱,且随着喂养时间的延长,血脂、胆固醇、血糖、胰岛素、IRI均渐进增高,而胰岛素敏感指数(ISI)降低,胰岛素抵抗形成,各组数据均与正常对照组有非常高度显著性差异(P<0.0001)。结论高脂喂养大鼠8周即可形成脂肪肝及胰岛素抵抗,致胰岛素活性和Lpl活性降低,脂肪分解障碍。

Objective To investigate the role of serine/threonine kinase （Akt） and lipoprotein lipase （Lpl） in formation of nonalcoholic steatohepatitis （NASH） in rat with a fat-rich diet. Methods 40 male Wistar rats were randomly divided into the 8-weekrich-fat group （n=10）, 8-week-common-diet control group （ n=10 ）, 12-week-rich-fat group （ n=10 ） and 12-week-common-diet control group （n= 10）. The lipid, cholesterol, glucose and insulin were examined, insulin resistance index （IRI） and insulin sensitivity index （ISI） were calculated, the expression of Akt and Lpl were detected with immunohistochemical method and morphological changes of liver were observed by transmission electron microscope （TEM）. Results NASH was formed in each rat of 8-week-rich-fat group with characteristics of individual obese, increased liver volume, full and clear contour, gray-yellowish luster, greasy section and crisp quality. And it was accompanied by high lipoidemia （HL）, liver fat cell denaturation, inflammatory cell infiltration in liver lobuler and cell death in liver. The expression of Akt was obviously reduced and the expression of Lpl was obviously weakened in liver. Lipid, cholesterol, glucose and insulin and IRI were gradually advancing. ISI was reducing and the insulin resistance formed. The data of fat-rich diet groups was significantly different with that of common-diet control groups （ P〈0. 0001 ）. Conclusion Steatohepatitis and insulin resistance can form in rat by feeding with rich-fat diet for 8 weeks. It causes the insulin and Lpl activeness reducing, and steatolysis barrier.