摘要
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 explore the relationship between Non-alcoholic fatty liver disease(NAFLD) and microsomal triglyceride transfer protein(MTP). Methods: 60 male Wistar rats were randomly divided into normal control group(group A), high fat group(group B), and MTP inhibitors group(group C). Group B and group C were given high fat feed. 8 weeks after successful establishment of the model of nonalcoholic fatty liver disease, the rats in group C was given high fat diet mixed with specificity of intestinal MTP inhibitor JTT-130, and the rats in high-fat group was fed high-fat feed all the time, while the rats of the control group was fed regular feed. After12 weeks, the levels of TG, TC, HDL-c in rat serum and TC, TG, phospholipid in the intestinal content were measured. And the activity and the m RNA expression of liver MTP was determined. Results: Compared with the normal control group, the levels of TG, TC, HDL-c in rat serum and TC, TG, phospholipid in the intestinal content in group B were higher than those in normal control group, and the difference was statistically significant(P〈0.05). The activity and m RNA levels of MTP were significantly decreased(P〈0.05). Compared with the high fat diet group(group B), the concentration of serum TC, TG, HDL-c and the TC, TG content in liver was decreased significantly in the rats of MTP inhibitor group(group C)(P〈0.05), and no significant differences of MTP activity and m RNA expression(P〉0.05). Conclusions: MTP expression is downregulated in non-alcoholic fatty liver disease, while the specific intestinal MTP inhibitor JTT-130 can effectively inhibit the intestinal transport of TG, but not affect the hepatic TG secretion, and it can also decrease plasma TG and cholesterol levels and TG content in liver of high fat rats.
出处
《现代生物医学进展》
CAS
2015年第27期5234-5237,共4页
Progress in Modern Biomedicine
基金
黑龙江省普通高等学校医学遗传学重点实验室开放课题资助(20101324)
哈尔滨市科技创新人才研究专项资金(2014RFXGJ043)