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目的探讨不同膳食脂肪酸构成对非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)发生、发展的影响及其与固醇调节元件结合蛋白-1c(SREBP-1c)的关系。方法 100只成年SD大鼠,按随机数字表法分为5组:对照组、NAFLD模型组、单不饱和脂肪酸组(monounsaturated fatty acid,MUFA)、n-6多不饱和脂肪酸组(n-6 polyunsaturated fatty acids,n-6 PUFA)和4∶1 n-6/n-3 PUFA组,每组20只。对照组用基础饲料喂养,其余各组饲料中加1%胆固醇和10%不同油脂(分别是10%猪油、10%橄榄油、10%玉米油、8%玉米油+2%鱼油)。分别于第8、16周时,采用HE染色观察肝脏脂肪变性情况,测定血清和肝脏中脂质含量,采用实时定量PCR分析SREBP-1c、FAS mRNA表达,Western blot检测SREBP-1c、FAS的蛋白表达。结果 NAFLD模型组大鼠体质量显著高于对照组和其他膳食脂肪酸组(P<0.05),模型组、MUFA组大鼠肝脏中TG含量显著高于对照组(P<0.05),而n-6 PUFA组和4∶1n-6/n-3 PUFA组大鼠血清中TG及肝脏中TC、TG浓度显著低于模型组(P<0.05);HE染色后,NAS量化评分显示模型组大鼠肝脏脂肪变性程度较对照组、MUFA组、n-6 PUFA组、4∶1 n-6/n-3 PUFA组严重;与对照组比较,NAFLD模型组大鼠肝脏SREBP-1c与FAS mRNA表达升高,MUFA组、n-6 PUFA组和4∶1 n-6/n-3 PUFA组SREBP-1c蛋白表达降低(P<0.05)。结论降低膳食中饱和脂肪酸,增加不饱和脂肪酸(尤其是适当比例的n-6/n-3 PUFA)可下调高脂喂养大鼠肝内SREBP-1c的表达,延缓高脂膳食引起的NAFLD发生、发展。
Objective To investigate the effect of dietary fatty acid composition on the occurrence and development of nonalcoholic fatty liver disease (NAFLD) and its relationship with steroid regulatory element binding protein-1c (SREBP-1c). Methods 100 adult SD rats were randomly divided into 5 groups: control group, NAFLD model group, monounsaturated fatty acid group (MUFA), n-6 polyunsaturated fatty acid group (n-6 polyunsaturated fatty acids, n-6 PUFA) and 4: 1 n-6 / n-3 PUFA groups, 20 in each. The control group was fed with basal diet, and the remaining groups were fed 1% cholesterol and 10% different fat (10% lard, 10% olive oil, 10% corn oil, 8% corn oil and 2% fish oil respectively). At the 8th and 16th week, the hepatic steatosis was observed by HE staining. The serum and liver lipid contents were determined. The expression of SREBP-1c and FAS mRNA was detected by real-time quantitative PCR. The protein expressions of SREBP-1c and FAS were detected by Western blot expression. Results The body weight of NAFLD model group was significantly higher than that of control group and other dietary fatty acid groups (P <0.05). The content of TG in liver of model group and MUFA group was significantly higher than that of control group (P <0.05) The levels of TG and TC, TG in the liver of PUFA group and 4:1n-6 / n-3 PUFA group were significantly lower than those of model group (P <0.05). After HE staining, NAS rat liver Compared with the control group, the levels of SREBP-1c and FAS mRNA in the liver of NAFLD model group were significantly higher than those in control group, MUFA group, n-6 PUFA group and 4:1 n-6 / n-3 PUFA group , SLEBP-1c protein expression in MUFA group, n-6 PUFA group and 4:1 n-6 / n-3 PUFA group decreased (P <0.05). Conclusions Reducing dietary saturated fatty acids and increasing unsaturated fatty acids (especially appropriate proportions of n-6 / n-3 PUFA) can reduce the expression of SREBP-1c in the liver of rats fed high fat diet and delay the occurrence of NAFLD induced by high fat diet. development of.