长期过量碘摄入对小鼠脂蛋白代谢影响

目的观察长期过量碘摄入对小鼠血清脂蛋白代谢影响。方法清洁级雌性断乳Balb/c小鼠60只,按体重随机分为6组(10只/组)。在饮水中以KIO3形式分别给予0(对照组),300,600,1200,2 400和4 800μg/L碘。30 d后,放射免疫法测定甲状腺激素,血清脂蛋白。PCR方法测定肝脏低密度脂蛋白受体(LDLR)、高密度脂蛋白受体(SR-BⅠ)基因表达水平。结果各剂量组小鼠尿碘水平随着碘剂量升高明显增加(P0.01),血清四碘甲状腺原氨酸(TT4)、三碘甲状腺原氨酸(TT3)、促甲状腺激素(TSH)水平未发生明显性改变。2 400,4 800μg/L组血清总胆固醇(TC)与低密度脂蛋白-胆固醇(LDL-C)含量分别为(2.40±0.37),(2.58±0.42)和(0.39±0.11),(0.41±0.11)mmol/L,与对照组比较,差异有统计学意义(P0.05)。LDLR mRNA表达水平呈碘剂量依赖性降低(r=-0.753,P0.01)。结论长期过量碘摄入可致小鼠血清LDL-C水平升高。LDLR受体表达降低可能是过量碘摄入导致脂蛋白代谢紊乱的机制之一。     

过量碘对大鼠血清TC和TG水平的影响

目的观察长期过量碘摄入对大鼠血清TC和TG水平的影响,并对其在评价过量碘危害中的意义进行探讨。方法将60只Wistar大鼠按体重随机分为6组:A组正常对照组,给予去离子水;B～F组为过量碘组,碘剂量分别为1800、3600、7200、14000和28000μgL,喂饲以KIO3配制成不同浓度的高碘水。3个月后,观察甲状腺病理变化,测定尿碘水平、血清甲状腺激素水平和血脂水平。结果各过量碘组大鼠甲状腺未出现明显病理组织学改变。各过量碘组大鼠的尿碘水平随着碘剂量的升高显著升高。TT4水平呈剂量依赖性的降低,在7200μgL组开始与对照组相比有显著性差异。TT3水平各组间无显著性差异。血清TC水平与碘剂量呈显著正相关,在3600μgL组就显著高于正常对照组。TG水平虽有升高,但各组间无显著性差异。血脂与甲状腺激素和尿碘水平的相关性分析表明,血清TC水平与尿碘水平呈显著正相关,与TT4水平呈显著负相关。结论长期过量碘摄入会升高大鼠血脂水平,血脂可以与尿碘、血甲状腺激素一起作为监测过量碘摄入的生物标志物。     

谷豆复合物、谷豆复合膳食纤维及单一谷物膳食纤维对脂代谢紊乱的影响

目的观察谷豆复合物、谷豆复合膳食纤维和全谷物玉米膳食纤维(DF)对脂代谢紊乱大鼠血脂及肝脏脂肪酸合成酶(FAS)活性,及其对大鼠肝组织固醇调节元件结合蛋白-1c(SREBP-1c)mRNA表达的影响,比较谷豆复合物、谷豆复合DF与单一谷物DF改善脂毒性效果。方法 50只SD大鼠适应性喂养1周后,随机分成阴性对照组、高脂模型组、谷豆复合物组、谷豆复合DF组和玉米DF组;以相应的饲料连续喂养8周后,测定各组大鼠总胆固醇(TC)、甘油三酯(TG)、空腹血糖(FBG)、高密度脂蛋白胆固醇(HDL-C)和FAS等指标,测定各组大鼠肝脏SREBP-1c mRNA的表达。结果与阴性对照组相比,高脂模型组的大鼠血清TC、TG水平显著升高(P0.05);与高脂模型组相比,谷豆复合物组、谷豆复合DF组和玉米DF组大鼠血清TC、TG水平显著降低(P0.05);HDL-C水平显著高于高脂模型组,大鼠肝脏脂肪酸合成酶活性及SREBP-1c的表达显著降低。结论谷豆复合膳食纤维可改善脂代谢紊乱大鼠的血脂水平,降低FAS活性及SREBP-1c的表达水平。     

过量碘对甲状腺激素代谢的损伤及硒的干预作用

目的研究过量碘性甲状腺激素代谢紊乱的机制并寻求合适的硒干预剂量。方法140只Balb/c小鼠分为7组:正常组、过量碘组(饮水含碘3000μg/L)和5个补硒组(饮水含碘3000μg/L,硒分别为0.1、0.2、0.3、0.4和0.5mg/L),共喂养16周。放射免疫法测定血清甲状腺激素水平,砷铈催化分光光度法测定尿碘和甲状腺碘水平,测定甲状腺谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)和甲状腺过氧化物酶(TPO)活性以及丙二醛(MDA)水平。结果0.1～0.5mg/L补硒组甲状腺激素水平与正常组比较差异无显著性,0.2mg/L补硒组甲状腺内碘含量较过量碘组显著下降(P<0.05),0.2～0.3mg/L补硒组甲状腺GSH-Px、SOD活性和MDA水平与正常组比较差异无显著性,0.1～0.3mg/L补硒组TPO活性与正常组比较差异无显著性。结论补充硒对过量碘导致的小鼠甲状腺氧化/抗氧化水平失衡、TPO活性水平下降都有有效的干预作用。     

硒对小鼠过量碘性1型脱碘酶损伤的干预作用研究

目的研究过量碘性甲状腺损伤的机制并寻求合适的硒干预剂量。方法160只BALB/c小鼠分为8组:正常组、过量碘组(饮水含碘3000μg/L)和6个补硒组(饮水含碘3000μg/L,硒分别为0.1、0.2、0.3、0.4、0.5和0.75mg/L),共喂养16周。测定肝脏、肾脏和甲状腺组织1型脱碘酶(D1)活性,逆转录聚合酶链反应技术测定D1mRNA水平。结果与正常组比较,过量碘组D1活性、mRNA水平下降,而补充0.1～0.4mg/L硒组上述指标与正常组差异无显著性。结论D1活性、mRNA水平下降可能是过量碘性甲状腺损伤的机制之一,而补充硒应选择合适的干预剂量。     

高碘对仔鼠脑甲状腺激素的影响及硒的干预作用

目的研究高碘摄入对小鼠仔鼠脑组织甲状腺激素的影响及硒的干预作用。方法将60只Balb/c小鼠随机分为4个不同的饮水组:正常对照组、高碘组(3000μg/L)、单独补硒组(200μg/L)、高碘加硒组(I3000μg/L+Se200μg/L)。喂养4个月时,雌雄交配。测定14和28日龄仔鼠血清TSH和甲状腺激素水平以及0、14和28日龄仔鼠大脑组织甲状腺激素水平。结果14日龄仔鼠高碘组血清TT4水平显著低于对照组和高碘加硒组,而TSH水平显著高于对照组和高碘加硒组(P<0·05),高碘组0和14日龄仔鼠脑组织甲状腺激素含量显著低于对照组、单独补硒组和高碘补硒组(P<0·05),28日龄仔鼠血清和脑组织甲状腺激素含量各组间差异无统计学意义。结论补硒能缓解高碘所致仔鼠脑组织甲状腺激素的改变。     

乳清酸诱导大鼠脂肪肝的机制研究

目的研究乳清酸诱发大鼠脂肪肝的机制。方法将大鼠分成两组,对照组喂食AIN93标准饲料,模型组饲料中添加1%乳清酸。饲喂10d后,分别测定大鼠血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、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。同时测定了肝脏中脂肪酸合成酶(FAS)、肉碱棕榈酰转移酶(CPT)、微粒体甘油三酯转运蛋白(MTP)的活性和其mRNA表达量,以及固醇调节元件结合蛋白(SREBP-1c)和过氧化物酶体增殖物激活受体(PPARα)的mRNA表达量。结果乳清酸可显著提高大鼠血清TG浓度和肝脏TC、TG含量。添加乳清酸后,大鼠肝脏中FAS活性及mRNA水平明显上调,而CPT、MPT活性及mRNA水平明显下调,同时作为转录调节因子的SREBP-1cmRNA表达量增加3.13倍,PPARα mRNA表达量无明显变化。结论1%乳清酸诱发大鼠脂肪肝与SREBP-1c的表达量升高引发的脂肪合成亢进有关,并与脂肪酸氧化分解受抑制及MTP活性和基因表达量降低有关。     

石榴鞣花酸对高脂血仓鼠肝脏脂质合成与分解基因表达的影响

目的观察石榴鞣花酸(PEA)对饮食诱导性高脂仓鼠脂质合成与分解相关基因的影响,探讨PEA降脂的作用机制。方法采用HPLC法测定PEA主要成分;54只雄性仓鼠随机均分为6组:正常对照组(NG,8w普通饲料);五个高脂组(HFG):模型对照组(MG)、药物对照组(辛伐他汀1.77mg/kg bw,SG)、PEA低(PEA-L 44 mg/kg bw)、中(PEA-M 88 mg/kg bw)、高(PEA-H 177 mg/kg bw;)剂量组,后5组为前4w高脂饲料,后4w普通饲料;4w高脂模型建立成功后,以灌胃方式连续给予仓鼠对应处理,第4w、8w检测仓鼠血清TC、TG含量;采用RT-PCR法测定肝脏中脂质代谢调控因子固醇调节元件结合蛋白-1c(SREBP-1c)m RNA表达和脂肪酸合成酶(FAS)以及脂蛋白脂肪酶(LPL)m RNA表达量。结论 PEA可以降低血液中TC、TG的含量,升高HDL-C的含量,主要通过抑制SREBP-1c m RNA、FAS m RNA的基因表达,促进LPL m RNA的基因表达实现降脂功能。PEA降脂效果存在剂量依赖关系,高剂量PEA效果较好。     

全小麦纤维对载脂蛋白E基因敲除小鼠肝脏脂代谢的影响

目的 探讨全小麦纤维通过改善肝脏脂代谢发挥抗动脉粥样硬化(AS)的作用及机制。方法 20只7周龄雄性载脂蛋白E基因敲除(ApoE~(-/-))小鼠,按体重随机分为AS模型组和全小麦纤维组,同时选相同遗传背景的C57BL/6小鼠作为空白对照组。预防性干预18周后,取主动脉和肝脏进行HE染色,肝匀浆行总胆固醇(TC)、甘油三酯(TG)和游离脂肪酸(FFAs)测定;蛋白质印迹法(Western blot)测定肝脏组织中胆固醇调节元件结合蛋白-1(SREBP-1)、脂肪酸合成酶(FAS)、乙酰辅酶A羧化酶(ACC)以及SREBP-2、低密度脂蛋白受体(LDLR)和B族1型清道夫受体(SR-B1)的蛋白表达水平。结果 实验结束时,与空白对照组相比,AS模型组小鼠主动脉内膜明显增生,管腔内大量泡沫细胞和无结构样坏死物,全小麦纤维组小鼠管腔内泡沫细胞减少,粥样斑块面积明显减少;AS模型组小鼠肝脏有明显的肝细胞脂肪变性,全小麦纤维组小鼠肝脏脂肪空泡的数目明显减少,肝细胞脂肪变性有所改善;与AS模型组相比,全小麦纤维组肝匀浆TC水平降低[(60.56±13.49)μmol/g vs.(51.10±5.94)μmol/g](P<0.05);肝脏组织中SREBP-1、FAS、ACC的蛋白表达量降低(P<0.05),SREBP-2和SR-B1的蛋白表达量增加(P<0.05)。结论 全小麦纤维可通过调控参与肝脏脂代谢相关蛋白的表达,改善肝脏脂代谢,发挥抗AS作用。     

高碘致仔鼠脑甲状腺激素代谢异常及硒的干预作用

目的:研究高碘摄入对小鼠子代脑甲状腺激素代谢的影响及硒干预的适宜剂量。方法:将120只Balb/c小鼠随机分为8个饮水组:正常对照组、高碘组(3000μg/LI)、6个高碘加硒组(100、200、300、400、500、750μg/L)。饲养4个月时,雌雄交配。测定0d和14d仔鼠血清和脑组织甲状腺激素以及脑5’-脱碘酶和5-脱碘酶活性。结果:高碘组14d仔鼠血清TT4水平以及0d、14d仔鼠脑组织TT4、TT3和rT3含量显著低于对照组,脑5’-脱碘酶活性显著高于对照组,脑5-脱碘酶活性显著低于对照组。加硒200μg/L至400μg/L组可有效改善碘过量所致的脑甲状腺激素代谢异常。结论:适量补硒可有效干预碘过量引起的仔鼠脑甲状腺激素代谢异常。     

硒对高碘小鼠肝脏两种含硒酶的影响

目的:研究硒对高碘小鼠肝脏含硒酶的影响,探讨硒干预高碘危害的机制。方法:40只雌性Balb/c小鼠按体重随机分为4组:正常对照组(NC);高碘对照组(HI),饮用3.0mg/LI的高碘水;高碘+硒I组(HI+Se1),高碘水中补充0.5mg/LSe;高碘+硒II组(HI+Se2),高碘水中补充1.0mg/LSe。5个月后,观察甲状腺病理变化,测定血清总T4(TT4)、总T3(TT3)、反式T3(rT3)水平以及肝脏硒含量、谷胱甘肽过氧化物酶(GSH-Px)活性、1型脱碘酶(DI-1)活性及mRNA表达。结果:高碘组小鼠出现了弥漫胶质性甲状腺肿;与正常对照组相比,高碘组的血清TT4水平显著升高,TT3水平显著降低;而补硒可显著抑制TT4的升高和TT3的降低;高碘组肝脏硒含量降低,MDA含量显著升高,GSH-Px和DI-1活性分别降低了47%和33%,DI-1mRNA的表达也下调。而两个补硒组能显著升高肝硒含量,增强GSH-Px活性以及DI-1活性和表达,其中以0.5mg/L的硒剂量作用最为明显。结论:适当剂量的硒可通过影响含硒酶的活性和mRNA的表达来发挥对高碘危害的干预作用。     

Sasa borealis Stem Extract Attenuates Hepatic Steatosis in High-Fat Diet-induced Obese Rats

The aim of the current study is to examine the improving effect of Sasa borealis stem (SBS) extract extracts on high-fat diet (HFD)-induced hepatic steatosis in rats. To determine the hepatoprotective effect of SBS, we fed rats a normal regular diet (ND), HFD, and HFD supplemented with 150 mg/kg body weight (BW) SBS extracts for five weeks. We found that the body weight and liver weight of rats in the HFD + SBS group were significantly lower than those in the HFD group. Significantly lower serum total cholesterol (TC) and triglyceride (TG) concentrations were observed in the SBS-supplemented group compared with the HFD group. We also found that the HFD supplemented with SBS group showed dramatically reduced hepatic lipid accumulation compared to the HFD alone group, and administration of SBS resulted in dramatic suppression of TG, TC in the HFD-induced fatty liver. In liver gene expression within the SBS treated group, PPARα was significantly increased and SREBP-1c was significantly suppressed. SBS induced a significant decrease in the hepatic mRNA levels of PPARγ, FAS, ACC1, and DGAT2. In conclusion, SBS improved cholesterol metabolism, decreased lipogenesis, and increased lipid oxidation in HFD-induced hepatic steatosis in rats, implying a potential application in treatment of non-alcoholic fatty liver disease.     

Dietary sea cucumber cerebroside alleviates orotic acid-induced excess hepatic adipopexis in rats

ABSTRACT: BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease in industrialized countries. The present study was undertaken to explore the preventive effect of dietary sea cucumber cerebroside (SCC) extracted from Acaudina molpadioides in fatty liver rats. METHODS: Male Wistar rats were randomly divided into four groups including normal control group, NAFLD model group, and two SCC-treated groups with SCC at 0.006% and 0.03% respectively. The fatty liver model was established by administration of 1% orotic acid (OA) to the rats. After 10d, serum and hepatic lipid levels were detected. And the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were also determined. Besides, to gain the potential mechanism, the changes of key enzymes and gene expressions related to the hepatic lipid metabolism were measured. RESULTS: Dietary SCC at the level of 0.006% and 0.03% ameliorated the hepatic lipid accumulation in fatty liver rats. SCC administration elevated the serum triglyceride (TG) level and the ALT, AST activities in OA-fed rats. The activities of hepatic lipogenic enzymes including fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphatedehydrogenase (G6PDH) were inhibited by SCC treatment. And the gene expressions of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c) were also reduced in rats fed SCC. However, dietary SCC didn't affect the activity and mRNA expression of carnitine palmitoyltransferase (CPT) in liver. Besides, suppression of microsomal triglyceride transfer protein (MTP) activity was observed in SCC-feeding rats. CONCLUSIONS: These results suggested that dietary SCC could attenuate hepatic steatosis due to its inhibition of hepatic lipogenic gene expression and enzyme activity and the enhancement of TG secretion from liver.     

Potato pulps lowered the serum cholesterol and triglyceride levels in rats

In our previous study, we demonstrated that retrograded starch, a kind of resistant starch, of beans reduced serum lipid levels in rats. In this study, we examined whether retrograded starch in potato pulps could reduce serum lipid concentrations. Rats were given diets containing 15 g of retrograded starch in potato pulps from the Benimaru potato (BM) or Hokkaikogane potato (HK) in a 100 g diet for 4 wk. At the 4th week, the total cholesterol level in the serum in the BM group and serum triglyceride (TG) level in the HK group were significantly lower than those in the control group. In the BM group, the contents of fecal bile acids were significantly higher than those in the control group. On the other hand, in the HK group, the hepatic mRNA level of fatty acid synthase (FAS) was significantly lower than that in the control group. The FAS mRNA level correlated with the mRNA level of sterol regulatory element-binding protein-1c (SREBP-1c), a regulator of expression of FAS, positively. These results suggested that BM pulp promoted the excretion of bile acids, which resulted in a low concentration of serum cholesterol. On the other hand, HK pulp inhibited the synthesis of fatty acids at the mRNA levels of FAS and SREBP-1c, which might lead to a reduction of the serum TG level.     

Soy protein affects serum insulin and hepatic SREBP-1 mRNA and reduces fatty liver in rats

The consumption of soy protein was shown to reduce blood lipids in humans and other animal species. Furthermore, it was shown that the ingestion of soy protein maintains normal insulinemia. Thus, the purpose of the present study was to determine whether soy protein affects the synthesis of lipids in the liver through sterol-regulatory element binding protein-1 (SREBP-1) due to modulation of insulin levels. We first conducted a short-term study in which rats were fed a diet containing 18 g/100 g soy protein or casein for 10 d. Rats fed soy protein had significantly lower serum insulin concentrations than rats fed casein, and this response was accompanied by an elevation in hepatic SREBP-1 mRNA that was 53% lower than that in rats fed casein at d 10. The increase in SREBP-1 mRNA occurred 30 min after consumption of the casein mean, and increased steadily for the next 2 h. We then conducted a second study to assess the long-term effect of soy protein consumption for 150 d on hepatic SREBP-1 expression. Long-term consumption of soy protein maintained normal insulin concentrations compared with rats fed casein, which were hyperinsulinemic. Thus, rats fed the soy protein diet had significantly lower expression of SREBP-1 mRNA than rats fed the casein diet. Soy protein intake also reduced the expression of fatty acid synthase (FAS) and malic enzyme, leading to low hepatic lipid depots of triglycerides and cholesterol, whereas rats fed the casein diet developed fatty liver. These data suggest that soy protein regulates SREBP-1 expression by modulating serum insulin concentration, thus preventing the development of fatty liver.     

Dietary umbelliferone attenuates alcohol-induced fatty liver via regulation of PPARα and SREBP-1c in rats

This study investigated the effects of umbelliferone (UF) on alcoholic fatty liver and its underlying mechanism. Rats were fed a Lieber–DeCarli liquid diet with 36% of calories as alcohol with or without UF (0.05 g/L) for 8 weeks. Pair-fed rats received an isocaloric carbohydrate liquid diet. UF significantly reduced the severity of alcohol-induced body weight loss, hepatic lipid accumulation and droplet formation, and dyslipidemia. UF decreased plasma AST, ALT, and γGTP activity. UF significantly reduced hepatic cytochrome P450 2E1 activities and increased alcohol dehydrogenase and aldehyde dehydrogenase 2 activities compared to the alcohol control group, which resulted in a lower plasma acetaldehyde level in the rats that received UF. Chronic alcohol exposure inhibited hepatic AMPK activation compared to the pair-fed rats, which was reversed by UF supplementation. UF also significantly suppressed the lipogenic gene expression (SREBP-1c, SREBP-2, FAS, CIDEA, and PPARγ) and elevated the fatty acid oxidation gene expression (PPARα, Acsl1, CPT, Acox, and Acaa1a) compared to the alcohol control group, which could lead to inhibition of FAS activity and stimulation of CPT and fatty acid β-oxidation activities in the liver of chronic alcohol-fed rats. These results indicated that UF attenuated alcoholic steatosis through down-regulation of SREBP-1c-mediated lipogenesis and up-regulation of PPARα-mediated fatty acid oxidation. Therefore, UF may provide a promising natural therapeutic strategy against alcoholic fatty liver.     

碘过量对仔鼠脑突触素表达影响及硒干预作用

目的 研究碘过量摄入对小鼠仔鼠脑突触素表达影响及硒的干预作用.方法 将60只BALB/c小鼠随机分为4组:正常对照组(饮用自来水)、碘(Ⅰ)过量组(饮水3 000μg/L Ⅰ)、单独补硒(Se)组(饮水200μg/L Se)、碘过量加硒(饮水3 000 μg/L Ⅰ+200μg/L Se)组.饲养4个月后,雌雄交配.测定第14和28 d仔鼠血清总四碘甲状腺原氨酸(T_4)和总三碘甲状腺原氨酸(T_3)水平,分别用荧光定量聚合酶链式反应(PCR)和蛋白印迹试验(Western blot)测定仔鼠大脑组织突触素mRNA和蛋白的表达.结果 第14 d碘过量组仔鼠血清L_4水平为(68.78±11.10)nmol/L,明显低于正常对照组和碘过量加硒组的(100.85±11.47)和(93.15±12.10)nmol/L(P<0.05);其脑组织突触素mRNA相对量为(44.87±3.82),明显低于正常对照组、单独补硒组和碘过量加硒组的(58.34±8.13),(54.33±5.32),(49.89±7.46);其蛋白相对量为(0.64±0.02),明显低于正常对照组、单独补硒组和碘过量加硒组的(0.78±0.01),(0.76±0.01),(0.81±0.03)(P<0.05).碘过量和补硒对第28 d仔鼠血清T_4和T_3水平和脑组织突触素表达水平无明显影响.结论 碘过量引起仔鼠脑突触素表达异常,补硒有缓解作用.