下丘脑腹内侧核损伤性肥胖大鼠动力相脂肪代谢研究

目的 :　探讨下丘脑腹内侧核损伤性肥胖大鼠在肥胖形成动力相中脂肪合成与分解代谢的变化。方法 :　雌性 SD大鼠分为下丘脑腹内侧核损伤肥胖组 (VMH)和下丘脑腹内侧核非损伤对照组 (sham) ,于下丘脑腹内侧核损伤和伪性损伤 1 w后 ,留取肝脏、皮下脂肪、子宫外周和肠系膜脂肪组织以及腓肠肌分别测定脂肪合成和分解酶活性。结果 :　VMH组大鼠肝脏微粒体甘油三酯转运蛋白、肝脏以及子宫外周和肠系膜脂肪组织的磷脂酰磷酸水解酶、苹果酸酶、葡萄糖 - 6 -磷酸脱氢酶活性均高于对照组。与对照组相比 ,VMH组子宫外周和肠系膜脂肪组织激素敏感脂酶(HSL )活性没有变化 ,皮下脂肪组织的 HSL活性升高 ,相反腓肠肌的 HSL活性下降。在 VMH组 ,皮下脂肪组织、子宫外周脂肪组织、肠系膜脂肪组织以及腓肠肌中的脂蛋白脂酶活性均升高。结论 :　在动力相 ,VMH肥胖大鼠肝脏合成和转运甘油三酯能力 ,以及脂肪组织如子宫外周和肠系膜脂肪组织的脂质合成和储存增强 ;另一方面 ,肌肉组织和皮下脂肪组织的脂肪分解也增强。     

下丘脑腹内侧核损伤大鼠脂肪肝形成机制探讨

目的 :　探讨下丘脑腹内侧核损伤性肥胖大鼠脂肪肝形成机制。方法 :　雌性 SD大鼠分为下丘脑腹内侧核损伤肥胖组 (VMH)和下丘脑腹内侧核非损伤对照组 (sham) ,于下丘脑腹内侧核损伤和伪性损伤 1 w后 ,留取肝脏作形态学观察和测定肝脏甘油三酯、磷脂酰磷酸水解酶、苹果酸酶、葡萄糖 - 6 -磷酸脱氢酶及微粒体甘油三酯转运蛋白活性。结果 :　VMH组大鼠肝脏中甘油三酯的含量明显增高 ,是对照组的 1 .8倍 ,肝脏磷脂酰磷酸水解酶、苹果酸酶、葡萄糖 - 6 -磷酸脱氢酶活性均高于对照组。显微镜下 ,在 VMH肥胖组大鼠肝细胞中可见有大量的脂质颗粒 ,而其对照组肝细胞中并没有见到类似的脂质颗粒。 VMH肥胖组大鼠肝细胞的微粒体甘油三酯转运蛋白活性是对照组的 1 .1 5倍 ,而且肝脏微粒体甘油三酯转运蛋白活性与血浆胰岛素水平呈明显的相关关系 (R=0 .86 3 ,P<0 .0 5 )。结论 :　VMH肥胖大鼠肝脏甘油三酯的产生和微粒体甘油三酯转运蛋白活性均明显增高 ,但后者的增加程度明显低于前者 ,这样可能导致肝脏中产生的甘油三酯不能被微粒体甘油三酯转运蛋白及时从肝脏转运出去 ,而导致甘油三酯在肝脏中积累形成脂肪肝。     

下丘脑腹内侧核损伤性肥胖大鼠急性期脂肪代谢相关酶活性研究

目的 :　观察下丘脑腹内侧核损伤性肥胖大鼠在自由进食状态下脂肪合成与分解代谢的变化。方法 :　雌性 SD大鼠分为下丘脑腹内侧核损伤肥胖组 (VMH)和下丘脑腹内侧核非损伤对照组 (假手术 ) ,于下丘脑腹内侧核手术 1 w后 ,留取血样、肝脏、皮下脂肪、子宫外周和肠系膜脂肪组织以及腓肠肌分别测定生化指标、脂肪合成酶和分解酶活性。结果 :　在自由进食状态下VMH血清胰岛素水平显著高于对照组 ,而血浆游离脂肪酸显著低于对照组。大鼠肝脏微粒体甘油三酯转运蛋白 (MTP)、肝脏磷脂酰磷酸水解酶 (PAP)、苹果酸酶 (ME)、葡萄糖 - 6-磷酸脱氢酶(G6PDH)以及子宫外周脂肪组织 ME和肠系膜脂肪组织 ME、G6PDH的活性均高于对照组。与对照组相比 ,VMH组子宫外周、肠系膜脂肪组织和腓肠肌激素敏感脂酶 (HSL)活性没有变化 ,皮下脂肪组织的 HSL活性升高。在 VMH组 ,皮下脂肪组织、子宫外周脂肪组织、肠系膜脂肪组织以及腓肠肌中的脂蛋白脂酶活性均显著升高。结论 :　下丘脑腹内侧核损伤性肥胖大鼠自由进食状态下肝脏合成和转运甘油三酯能力增强 ,脂肪组织如子宫外周和肠系膜脂肪组织的脂质合成和储存增多 ;而外周组织如肌肉组织和皮下脂肪组织的脂肪分解和动员也增加     

葡萄糖对下丘脑腹内侧核损伤性肥胖大鼠脂质代谢的影响

大鼠下丘脑腹内侧核损伤性肥胖模型(ventromedial hypothalamus-lesioned obesity,VMH)是常用的肥胖模型 ,表现有肥胖、食欲亢进、高胰岛素血症、高甘油三酯血症 [1～ 3] 。血浆甘油三酯是形成肥胖的物质基础 ,它在脂蛋白脂酶的作用下 ,分解为游离脂肪酸和甘油 ,前者进入脂肪细胞重新酯化为甘油三酯而贮存[4 ] 。以往的研究已经证实VMH肥胖大鼠肝脏合成甘油三酯增加 [2 ] 。在 VMH肥胖的形成过程中 ,葡萄糖对甘油三酯的代谢有什么影响还不清楚 ,为此 ,利用静脉葡萄糖耐量实验探讨了葡萄糖对甘油三酯代谢的影响。1　材　料　与　方　法1 …     

饮食诱导肥胖抵抗和肥胖大鼠血中激素水平的比较

目的　研究饮食诱导肥胖抵抗 (DIO R)和肥胖 (DIO)大鼠血中胰岛素、瘦素 (leptin)和神经肽Y(NPY)水平的差别。方法　采用 5 0只健康雄性SD大鼠 ,随机分为基础组和高脂组 ,分别用基础饲料和高脂饲料喂养 13周 ,然后根据体重筛选出DIO R和DIO组 ,观察体重、摄食量和体脂含量的变化 ,放免法测血清胰岛素、leptin和血浆NPY含量。结果　DIO R大鼠体重、摄食量和体脂含量均明显低于DIO大鼠 (P <0 0 5 ) ;血清胰岛素、血浆NPY含量显著低于DIO大鼠 (P <0 0 5 ) ;高脂饲料使大鼠血清leptin水平明显增加 (P <0 0 5 ) ,但DIO R与DIO大鼠间无明显差别 (P >0 0 5 )。结论　高脂饲料能够诱导SD大鼠发生肥胖和肥胖抵抗 ,胰岛素 leptin NPY反馈环的平衡在肥胖抵抗的发生中起重要作用。     

吡非尼酮对大鼠矽肺纤维化的抑制作用

目的 探讨吡非尼酮(PFD)对大鼠矽肺纤维化的抑制作用.方法 75只SD雄性大鼠,随机分成未处理对照组、生理盐水组、生理盐水+PFD组、SiO2组、SiO2+PFD组,每组15只,采用非暴露式气管内染尘法,SiO2组和SiO2+PFD组注入SiO2粉尘悬液(25 mg/ml),生理盐水组和生理盐水+PFD组注入等量生理盐水,染尘后第2天灌胃给予PFD(50 mg/kg),分别观察7、21、42 d后处死.HE、VG和Foot染色观察肺组织的病理形态学改变并进行病理分级,测定肺组织中羟脯氨酸(HYP)的含量.结果 大鼠肺组织病理观察显示,SiO2+PFD组肺组织纤维化程度比同期SiO2组明显减轻,胶原纤维形成缓慢,矽结节分级评分降低.第42天时,SiO2+PFD组大鼠肺组织HYP含量[(0.75±0.12)mg/g肺组织]比SiO2组[(1.19±0.17)mg/g肺组织]明显降低,差异有统计学意义(P＜0.05).结论 PFD能降低大鼠矽肺纤维化程度并减少肺组织中HYP的含量,对实验性大鼠矽肺纤维化具有抑制作用.     

高脂饲料诱导肥胖及肥胖抵抗大鼠的瘦素、胰岛素水平

目的:探讨高脂饲料肥胖诱导大鼠的瘦素、胰岛素水平与肥胖抵抗的关系。方法:将50只雄性Wistar大鼠随机分为肥胖诱导组和正常对照组,分别喂以高脂饲料和基础饲料8周,观察体脂含量的变化,第8周末根据体重增加量筛选出膳食诱导肥胖(DIO)组大鼠和膳食诱导肥胖抵抗(DIO-R)组大鼠,采用酶法测定血脂4项,酶联免疫法测定瘦素和胰岛素水平并进行比较。结果:高脂饲料喂养导致肥胖组和肥胖抵抗组大鼠的血清总胆固醇、低密度脂蛋白胆固醇、瘦素和胰岛素水平均显著高于正常对照组,也使肥胖组大鼠体重显著高于肥胖抵抗组与正常对照组大鼠,肥胖抵抗组大鼠体重和正常对照组比较没有差异。结论:高脂饲料诱导肥胖抵抗大鼠不易产生瘦素抵抗和胰岛素抵抗,但伴有一定程度的血脂代谢紊乱。     

共轭亚油酸对肥胖大鼠PPARγ基因表达及血清瘦素水平的影响

目的　研究不同剂量共轭亚油酸 (CLA)对饮食诱导肥胖大鼠PPARγ基因、瘦素、血糖、血脂的影响。方法　选用雄性Wistar大鼠 ,随机分为对照组、高脂组、高脂 +CLA组 (每 10 0g饲料含CLA分别为 0 75g、1 5 0g、3 0 0g) ,于第 12周末处死动物 ,计算脂 体比 ,测定大鼠血糖、血脂及瘦素水平 ,并应用RT PCR的方法检测大鼠白色脂肪组织过氧化物酶体增殖物激活受体γ(PPARγ)的表达水平。结果　CLA可降低肥胖大鼠血糖、甘油三酯 (TG)、总胆固醇 (TC)及瘦素水平 ,增加脂肪组织PPARγmRNA的表达水平。结论　CLA可降低肥胖大鼠血糖、血脂 ,并可通过激活PPARγ下调瘦素水平 ,有改善肥胖大鼠的瘦素抵抗作用。     

细胞因子信号转导抑制因子3基因沉默对高脂喂养肥胖幼年大鼠的影响

目的 观察RNA干扰(RNA interference, RNAi)沉默细胞因子信号转导抑制因子3(suppressor of cytokine signaling3, SOCS3)能否改善高脂喂养幼年大鼠的肥胖和瘦素抵抗。方法 32只5周龄健康雄性SD大鼠, 随机分为4组干扰+普食组, 对照+普食组, 干扰+高脂组, 对照+高脂组, 每组各8只。侧脑室注射慢病毒载体SOCS3干扰液或慢病毒载体对照液, 然后给予高脂或普通饲料喂养28 d, 期间测摄食量和体重。处死后取血, 放射免疫法测瘦素(leptin)含量, 全自动生化分析仪测血糖(plasma glucose, PG)、总胆固醇(total cholesterol, TC)、甘油三脂(triglycerides, TG)水平。结果 干扰+高脂组大鼠的摄食量和体重分别于注射后第14天和第21天起低于对照+高脂组(P＜0.05);于注射后第22天起和第28天高于对照+普食组(P＜0.05)。干扰+高脂组大鼠瘦素水平(0.86±0.12)ng/mL低于对照+高脂组(0.97±0.13)ng/mL, 高于对照+普食组(0.75±0.10)ng/mL(P＜0.05)。结论 SOCS3基因沉默可改善幼年大鼠高脂喂养诱导的肥胖和瘦素抵抗。     

营养性幼年肥胖雌性大鼠模型的建立

[目的]模拟营养性肥胖儿童的饮食特点,建立一种适合儿童肥胖研究的幼年大鼠营养性肥胖模型。[方法]将30只SD雌性刚离乳大鼠按体重随机分成模型组和对照组,模型组给予改良的高酯饲料喂养,对照组给予普通饲料喂养,8周后测定两组组大鼠的体重、体长和血清瘦素指标。[结果]8周后模型组的体重为和血清瘦素水平分别为(276±15.59)g,(3.60±0.49)μg/L,对照组的体重和血清瘦素水平分别为(252±19.93)g,(3.20±0.36)μg/L,经统计学检验模型组的均高于对照组(P均﹤0.05);而两组的体长差异无统计学意义(P﹥0.05)。[结论]改良的高脂饲料配方组成较为合理,致肥率为50%,致肥效果较好。     

限制进食对下丘脑腹内侧核损伤性肥胖大鼠体重反弹的影响

目的：探讨限制进食后体重快速回升的机理。方法：下丘脑腹内侧核损伤性（ＶＭＨ）肥胖大鼠给予其正常进食量的５０％饲养６天后,收集血样,分析胆固醇、甘油三酯、游离脂肪酸、血浆消瘦素、胰岛素和脂蛋白脂酶的水平和活性。结果：在限制进食后,ＶＭＨ肥胖大鼠体重和血浆消瘦素、胆固醇、甘油三酯以及游离脂肪酸明显下降;肝脏分泌甘油三酯减少,同时血浆中甘油三酯清除加快。但是,血浆胰岛素水平和肝素后脂蛋白脂酶活性并没有下降,仍然维持在很高的水平上。结论：虽然限制进食能够减轻体重、体内脂肪量,降低血浆胆固醇、甘油三酯浓度,但并不能降低血浆胰岛素水平和脂蛋白酯酶活性,即不能消除或减轻脂肪合成亢进的危机。这是停止限制进食、转入正常进食后,体重快速回升的生化基础。     

Effect of a high-protein diet on insulin and glucagon secretion in ventromedial hypothalamic (VMH) lesioned rats

The effects of a high-protein diet on insulin and glucagon secretion in ventromedial hypothalamic (VMH) lesioned and sham-operated (sham) rats were studied in vivo as well as in perfusate from isolated pancreas. Two weeks after VMH destruction or sham operation, the rats were given either a balanced diet (protein 27%, carbohydrate 61%, fat 12%) or a high-protein diet (protein 55%, carbohydrate 30%, fat 15%) for the following 2 weeks. The calorie intake and body weight changes after the commencement of the diets were almost the same in the groups of VMH lesioned rats, but these were much greater than those in the two sham-operated groups. Fasting blood glucose, plasma insulin, and plasma glucagon concentrations were also similar between the two VMH groups, but in the sham-operated rats fasting blood glucose and plasma insulin concentrations of those rats on high-protein diet were significantly increased when compared to those on balanced diet. In the isolated, perfused pancreas, an arginine-induced excess insulin and glucagon secretion was not significantly different between the VMH lesioned rats. An arginine-induced rise in insulin concentration in the sham-operated rats on high-protein diet was significantly higher than for rats on balanced diet. We therefore suggest that hyperinsulinemia already produced in the VMH lesioned rats may not be influenced by the change in the composition of the dietary protein and carbohydrate.     

下丘脑腹内侧核损伤性肥胖大鼠氨基酸代谢的变化

目的　探讨下丘脑腹内侧核损伤性肥胖大鼠氨基酸代谢的变化。方法　下丘脑腹内侧核损伤性肥胖大鼠用 2 m A直流电造成下丘脑腹内侧核损伤后 1、2、4、6、1 0及 1 2周收集血样 ,分析血清氨基酸、葡萄糖及甘油三酯浓度。结果　 (1 )损伤后 1 2周 ,肥胖大鼠的血清葡萄糖和甘油三酯浓度明显增高 ;(2 )肥胖大鼠的血清支链氨基酸即缬氨酸、亮氨酸及异亮氨酸明显高于非肥胖组 ;(3)肥胖大鼠血清中的一些生糖性氨基酸如苏氨酸、甘氨酸、丙氨酸明显增高 ;(4)肥胖大鼠的血清精氨酸水平随肥胖的发展而呈进行性下降。结论　下丘脑腹内侧核损伤性肥胖大鼠不仅血糖、血脂代谢紊乱 ,而且氨基酸代谢发生了异常的改变。     

Neonatal leptin treatment programmes leptin hypothalamic resistance and intermediary metabolic parameters in adult rats

We previously showed that neonatal leptin treatment programmes higher body weight and food intake in adult rats. Here we investigate whether leptin treatment during lactation affects the anorectic effect of leptin on adult rats and their hypothalamic leptin receptors (OB-Rb) and whether those changes could have consequences on intermediary metabolism. When the offspring were born, pups were divided into two groups: the Lep group, injected daily with leptin (8 microg/100 g body weight, subcutaneously) for the first 10 d of lactation, and the control group, injected daily with saline. After weaning (day 21), body weight and food intake were monitored until the rats were 150 d old. Food intake was higher in the Lep group (approximately 14 %, P<0.05) from day 133 onwards, and body weight was higher (approximately 10 %, P<0.05) from day 69 onwards, compared with the control group. At 150 d of age, the rats were tested for food intake in response to either leptin (0.5 mg/kg body weight intraperitoneally; groups CL and LepL) or saline (groups CSal and LepSal). The CL group showed a decrease in food intake, but no response was observed in the LepL group, suggesting leptin resistance. The Lep group demonstrated a decrease in OB-Rb expression (-40 %, P<0.05), hyperleptinaemia (+78 %, P<0.05), hyperinsulinaemia (+100 %, P<0.02), hypertriacylglycerolaemia (+17 %, P<0.05) and a higher protein content in the body (+16 %, P<0.05) without changes in fat mass and glycaemia. We conclude that neonatal leptin treatment programmes both hyperleptinaemia and hyperinsulinaemia in adulthood, which leads to leptin resistance by reducing the expression of the hypothalamic leptin receptor.     

大豆异黄酮对肥胖大鼠血脂及瘦素水平的影响

目的：通过大豆异黄酮（SIF）对肥胖大鼠的干预，观察大鼠体重、血脂及血清瘦素水平的变化，探讨SIF对肥胖大鼠的减肥作用及机制。方法：用高脂饲料造成雄性大鼠肥胖模型，然后按体重将其随机分为4组，各组均继续给予高脂饲料。其中一组为肥胖对照组，灌胃生理盐水，另外三组灌胃SIF，剂量分别为50mg／kg BW、150mg／kg BW及450mg／kg BW。第4周末股动脉取血，用酶免法检测血浆中瘦素，酶法检测血脂。结果：与肥胖对照组相比，450mg／kg BW剂量组大鼠血清瘦素水平明显升高，大鼠体重、血清TG、TC水平降低（P〈0．05或P〈0．01）；150mg／kg BW剂量组大鼠的体重及血清TC水平降低（P〈0．05）。结论：SIF对肥胖大鼠有减肥作用，机制可能与SIF调节瘦素表达和分泌有关。     

Ventromedial and lateral hypothalamic injections of naloxone or naltrexone suppress the acute food intake of food-deprived rats

Experiments were conducted to determine the anorexigenic effects of ventromedial (VMH) and lateral hypothalamic (LH) injections of the mu-opiate receptor antagonists, naloxone and naltrexone, on food-deprived (20 h) rats. Lever pressing to obtain food pellets was measured in groups of hungry, male Sprague-Dawley rats following VMH, LH or subcutaneous (SC) injections of saline, naloxone or naltrexone. VMH injections of either narcotic antagonist (5 and 10 micrograms/microliter) and LH injections of naloxone (5 and 10 micrograms/microliter) decreased the total 90-min food intake, compared to saline controls, due to suppressed feeding especially during the initial 30-min interval. Rats given SC injections of naloxone (10 mg/kg) also decreased their food intake compared to amounts eaten after SC saline was given. Decrements in food consumption relative to saline controls were similar following VMH or LH administration of naloxone. Moreover, the anorexia observed following VMH naloxone administration was similar to that found after VMH injections of equal doses of naltrexone.     

Dietary supplementation with conjugated linoleic acid plus n-3 polyunsaturated fatty acid increases food intake and brown adipose tissue in rats

The effect of supplementation with 1% conjugated linoleic acid and 1% n-3 long chain polyunsaturated fatty acids (CLA/n-3) was assessed in rats. Food intake increased with no difference in body weights. White adipose tissue weights were reduced whereas brown adipose tissue and uncoupling protein-1 expression were increased. Plasma adiponectin, triglyceride and cholesterol levels were reduced while leptin, ghrelin and liver weight and lipid content were unchanged. Hypothalamic gene expression measurements revealed increased expression of orexigenic and decreased expression of anorexigenic signals. Thus, CLA/n-3 increases food intake without affecting body weight potentially through increasing BAT size and up-regulating UCP-1 in rats.     

Leptin suppresses food intake and body weight in corticosterone-replaced adrenalectomized rats

Intracerebroventricular (ICV) injections of leptin decrease food intake and body weight while increasing energy expenditure. Some of these effects are reportedly enhanced in bilaterally adrenalectomized (ADX) rats. The purpose of the present experiment was to establish the time course of the suppression in body weight and food intake after an ICV injection of leptin. We wanted to establish the effect of varying doses of corticosterone (CORT) on body weight and food intake suppression by using separate groups of ADX, ADX and corticosterone-treated and sham-operated Sprague-Dawley rats. All rats were implanted with cholesterol pellets that varied in CORT content. During the same surgical session, all rats were fitted with a cannula in the lateral ventricle. After recovering from surgery, each rat was administered a 5- micro g ICV injection of leptin. ADX rats that were treated with CORT replacement lost more (P < 0.05) weight and took longer (P < 0.05) to return to baseline body weight than sham-operated controls. Leptin injection decreased food consumption to a greater extent (P < 0.05) in the ADX groups treated with CORT than in the sham-operated controls. Plasma insulin increased in a dose-dependent manner in the ADX rats as a function of CORT replacement. The higher of the two CORT replacement doses used in this experiment restored circulating CORT to levels observed in sham-operated controls. Contrary to earlier reports, physiological doses of CORT appear to enhance leptin-induced weight loss.