下丘脑腹内侧核损伤大鼠脂肪肝形成机制探讨

STUDY ON MECHANISM OF FATTY LIVER IN VENTROMEDIAL HYPOTHALAMUS(VMH)-LESIONED OBESE RATS

目的 : 探讨下丘脑腹内侧核损伤性肥胖大鼠脂肪肝形成机制。方法 : 雌性 SD大鼠分为下丘脑腹内侧核损伤肥胖组 (VMH)和下丘脑腹内侧核非损伤对照组 (sham) ,于下丘脑腹内侧核损伤和伪性损伤 1 w后 ,留取肝脏作形态学观察和测定肝脏甘油三酯、磷脂酰磷酸水解酶、苹果酸酶、葡萄糖 - 6 -磷酸脱氢酶及微粒体甘油三酯转运蛋白活性。结果 : VMH组大鼠肝脏中甘油三酯的含量明显增高 ,是对照组的 1 .8倍 ,肝脏磷脂酰磷酸水解酶、苹果酸酶、葡萄糖 - 6 -磷酸脱氢酶活性均高于对照组。显微镜下 ,在 VMH肥胖组大鼠肝细胞中可见有大量的脂质颗粒 ,而其对照组肝细胞中并没有见到类似的脂质颗粒。 VMH肥胖组大鼠肝细胞的微粒体甘油三酯转运蛋白活性是对照组的 1 .1 5倍 ,而且肝脏微粒体甘油三酯转运蛋白活性与血浆胰岛素水平呈明显的相关关系 (R=0 .86 3 ,P<0 .0 5 )。结论 : VMH肥胖大鼠肝脏甘油三酯的产生和微粒体甘油三酯转运蛋白活性均明显增高 ,但后者的增加程度明显低于前者 ,这样可能导致肝脏中产生的甘油三酯不能被微粒体甘油三酯转运蛋白及时从肝脏转运出去 ,而导致甘油三酯在肝脏中积累形成脂肪肝。

Objective: To investigate how fatty liver was developed in ventromedial hypothalamus(VMH)-lesioned obese rats. Methods: Two groups of rats were prepared: (1)VMH-lesioned obese rats, and (2)sham VMH-lesioned rats. One week after VMH lesions, livers of all rats were isolated for morphological observation and for determination of microsomal triglyceride transfer protein(MTP), phosphatidate phyosphohydrolase (PAP), malic enzyme (ME), and glucose-6-phosphate dehydrogenase(G6PDH). Results: Triglyceride contents in livers of VMH-lesoned obese rats increased significantly, and were about 1.8-fold of control group. Activities of ME, G6PDH and PAP in the livers were also enhanced markedly compared to their controls. Many lipid droplets in cytoplasm of hepatocytes from VMH-lesioned obese rats were observed, while there was no similar finding in hepatocytes of control rats. MTP activity in livers of VMH-lesioned obese rats was higher than that in livers of sham-operated non-obese rats [0.201±0.013 vs. 0.175±0.014 μg/(mg protein·h),[WTBX]P<0.01], and increased about 1.15-fold. In VMH-lesioned rats, MTP activity was correlated to its plasma insulin concentrations (R=0.863, , and increased about 1.15-fold. In VMH-lesioned rats, MTP activity was correlated to its plasma insulin concentrations (R=0.863, P<0.05). Meanwhile in sham group, no similar result was observed (R=0.056, P>0.05). Conclusion: Hepatic triglyceride production and activity of MTP were increased in VMH-lesioned obese rats, but magnitude of the latter did not exceed the former. This resulted in hepatic triglyceride accumulation in spite of increase in transport of triglyceride out of liver by MTP. This may contribute to the development of fatty liver in VMH-lesioned obese rats.