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目的:探讨非酒精性脂肪性肝病(Non-alcoholic fatty liver disease,NAFLD)与微粒体甘油三酯转运蛋白(microsomal triglyceridetransfer protein,MTP)的关系。方法:将雄性Wistar大鼠60只随机分为正常对照组(A组)、高脂组(B组)和MTP抑制剂组(C组),每组各20只。B组、C组给予高脂饲料喂养,8周后确认非酒精性脂肪肝建模成功,C组大鼠给予混有特异性小肠MTP抑制剂JTT-130的高脂饲料喂养,B组大鼠建模过程始终喂养高脂饲料,A组大鼠喂养普通饲料。于第12周,分别测定大鼠血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-c)含量,以及肝脏TC、TG、磷脂含量。同时测定肝脏中微粒体甘油三酯转运蛋白(MTP)的活性与m RNA表达量。结果:与正常对照组(A组)相比,高脂组(B组)大鼠血清TC、TG、HDL-c浓度和肝脏TC、TG含量明显提高(P<0.05),MTP活性及m RNA水平明显下调(P<0.05)。与高脂组(B组)比较,MTP抑制剂组(C组)大鼠血清TC、TG、HDL-c浓度和肝脏TC、TG含量明显下降(P<0.05),而MTP活性及m RNA表达量比较无明显差别(P>0.05)。结论:非酒精性脂肪性肝病存在MTP表达下调,特异性小肠MTP抑制剂JTT-130可以有效抑制肠道对TG的转运,不影响肝脏TG分泌,并在降低高脂大鼠血浆TG和胆固醇水平的同时也降低肝脏TG含量。
Objective: To investigate the relationship between non-alcoholic fatty liver disease (NAFLD) and microsomal triglyceride transfer protein (MTP). Methods: Sixty male Wistar rats were randomly divided into normal control group (group A), high fat group (group B) and MTP inhibitor group (group C), 20 rats in each group. Groups B and C were fed with high-fat diet, and non-alcoholic fatty liver was confirmed 8 weeks later. Rats in group C were fed with high-fat diet mixed with specific intestinal MTP inhibitor JTT-130. Rats in group B The modeling process always fed high fat diet, group A rats fed normal feed. At week 12, the levels of triglyceride (TG), total cholesterol (TC) and high density lipoprotein-cholesterol (HDL-c) TG, phospholipid content. Simultaneously, the microsomal triglyceride transporter (MTP) activity and m RNA expression in the liver were measured. Results: Compared with normal control group (group A), serum TC, TG and HDL-c levels and liver TC and TG levels were significantly increased (P <0.05), MTP activity and m RNA Level was significantly lower (P <0.05). The levels of TC, TG, HDL-c and TC, TG in liver of rats in MTP inhibitor group (C group) were significantly decreased compared with those in high fat group (P <0.05), while MTP activity and m RNA expression There was no significant difference (P> 0.05). CONCLUSIONS: MTP expression is down-regulated in non-alcoholic fatty liver disease. Specific intestinal MTP inhibitor JTT-130 can effectively inhibit intestinal transit of TG, does not affect hepatic TG secretion, and decreases plasma TG and cholesterol levels It also reduces liver TG levels.