糖尿病小鼠肝脏脂肪酸合成酶的动态表达

Dynamic expression of fatty acid synthase in the liver of diabetic mouse

关键词:  糖尿病  脂代谢紊乱  脂肪酸合成酶

Key words:  diabetes  dyslipidemia  fatty acid synthase

摘要:

目的　观察1型、2型糖尿病小鼠肝脏脂肪酸合成酶(fatty acid synthase, FAS)表达的改变，探讨其在糖尿病肝脏脂质代谢紊乱中的意义。方法　〖ＨＴＫ〗1型糖尿病小鼠模型以链脲佐菌素（streptozotocin，STZ）诱导，对照组小鼠应用等量生理盐水。2型糖尿病小鼠模型选取C57BL/6基因背景下瘦素受体基因缺陷小鼠，纯合子db/db小鼠入选实验组；杂合子db/m小鼠入选对照组。应用免疫组化法检测FAS在肝脏定位；应用Real-time PCR技术、Western 印迹方法，分别从mRNA水平、蛋白水平检测FAS在1型、2型糖尿病小鼠肝脏表达的变化。结果　〖ＨＴＫ〗FAS蛋白在肝脏广泛表达，主要位于肝细胞的胞浆内。1型糖尿病小鼠HbA1c水平（5.45±0.56）%明显高于对照组（2.93±0.08）%（P<0.05），血甘油三酯（triglyceride，TG）水平（2.25±0.66）mmol/L高于对照组（0.99±0.46）mmol/L（P<0.05），血胆固醇（cholesterin，CHO）水平（1.90±0.12）mmol/L高于对照组（1.62±0.10）mmol/L（P<0.05）；FAS的mRNA水平约为对照组的1.4倍，FAS 在蛋白水平也明显高于对照组。2型糖尿病小鼠HbA1c水平（5.73±0.33）%明显高于对照组（3.90±0.07）%（P<0.05），db/db鼠也存在明显高脂血症，血TG水平（2.85±0.24）mmol/L高于对照组（0.87±0.40）mmol/L（P<0.05），血CHO水平（3.60±0.98）mmol/L高于对照组（1.73±0.50）mmol/L（P<0.05）；FAS mRNA水平约为对照组的2.7倍，蛋白印迹显示db/db鼠肝脏FAS也明显高于db/m鼠。结论　〖ＨＴＫ〗1型、2型糖尿病小鼠均存在不同程度的脂质代谢紊乱，其肝脏FAS的含量，无论从mRNA水平还是蛋白水平均较正常小鼠明显增高。

Abstract:

Objective　To investigate the expression of fatty acid synthase in the liver of type 1 and type 2 diabetic mouse. 　Methods　Type 1 diabetes mouse model induced by Streptozotocin and mouse in control group were given the same volume of NS. Leptin receptor-deficient (db/db) mouse on C57BL/6 background were used as type 2 diabetic mouse model and db/m were used as control. Immunostaining was used to detect the FAS protein expression in the liver. Real-time PCR and Western blot were used to detect the expression of FAS in the liver of diabetic mouse on mRNA and protein level. 　Results　FAS was abundantly expressed in liver, especially in cytoplasm of liver cells. Compared with the control group, type 1 diabetic mouse showed higher level of HbA1c, TG and CHO. The HbA1c levels were higher than that in control group（5.45±0.56）% vs （2.93±0.08）%; The serum TG levels were higher than that in control group（2.25±0.66）mmol/L vs （0.99±0.46）mmol/L. The serum CHO levels were higher than that in control group（1.90±0.12）mmol/L vs （1.62±0.10）mmol/L. The mRNA level of FAS in the liver of type 1 diabetic mouse was dramatic higher than control group, increased about 1.4 times. At the protein level, FAS in liver of type 1 diabetic mouse was increased compared with the control. Similarly with type 1 diabetic mouse, type 2 diabetic mouse showed higher level of HbA1c and dramatic hyperlipemia. The HbA1c levels were higher than that in control group （5.73±0.33)% vs (3.90±0.07)%; The serum TG levels were higher than that in control group （2.85±0.24)mmol/L vs (0.87±0.40)mmol/L. The serum CHO levels were higher than that in control group（3.60±0.98)mmol/L vs (1.73±0.50)mmol/L. FAS in liver of db/db mouse was induced about 2.7 times as much as that of db/m mouse at the mRNA level. At the protein level, FAS in liver of db/db mouse was increased compared with the control. 　Conclusion　There existed dyslipidemia in diabetic mouse including Type 1 and Type 2, Liver expression of FAS was increase in Type 1 and Type 2 diabetic mouse were increased control with control.