Effect of cyclic AMP on lipid accumulation and metabolism in human atherosclerotic aortic cells

The effects of dibutyryl cyclic AMP (db cAMP), cholera toxin, and methylisobutylxanthine on the content and metabolism of lipids in smooth muscle cells cultured from normal and atherosclerotic intima of human aorta have been studied. Db cAMP (0.1 mM) decreased the levels of triglycerides and esterified sterols 1.5-3-fold in cells cultured from fatty streaks and atherosclerotic plaques. Cholera toxin (100 micrograms/ml) and methylisobutylxanthine (0.1 mM) stimulated by 2-fold the cyclic AMP level in aortic smooth muscle cells and decreased the content of triglycerides and esterified sterols by 2-3-fold. Prolonged treatment with db cAMP and methylisobutylxanthine resulted in a fall in the intracellular phospholipids and free sterols. Using the labelled precursors, [3H]acetate and [14C]oleate, it was established that the agents increasing the intracellular cyclic AMP level inhibit the formation of sterols and fatty acids, impede the synthesis of phospholipids, triglycerides and esterified sterols, and stimulate their hydrolysis. The data demonstrate that cyclic AMP facilitates the regression of cellular lipoidosis by altering the intracellular lipid metabolism.     

活血降糖胶囊对动脉粥样硬化大鼠早期血管壁组织结构的影响

目的探讨活血降糖胶囊对动脉粥样硬化大鼠主动脉血管壁组织结构的影响。方法45只SPF级SD大鼠,随机取8只为空白组,其余以高脂高糖饮食加链脲佐菌素(STZ)诱导动脉粥样硬化(AS)模型。将成模大鼠分为模型组,西药组,中药低、高剂量治疗组,连续治疗1个月后,采用光镜和电镜观察各组大鼠主动脉内膜及血管平滑肌的形态。结果模型组主动脉内膜出现典型粥样硬化病变,中药治疗组动脉膜受损程度有所减轻。结论活血降糖胶囊对AS大鼠早期主动脉有保护作用。     

Effect of hypertension on lipid metabolism and beta-oxidation in rat aorta and brain microvessels

The effects of hypertension on various enzyme activities involved in lipid metabolism and beta-oxidation in rat brain microvessels and aorta were studied. The purity of the brain microvessel preparation was confirmed immunologically and microscopically. Activities involved in lipid synthesis, such as triacylglycerol synthesizing activity, acyl-CoA synthesizing activity, acyl-CoA: cholesterol acyltransferase and cytidine diphosphate choline:1,2-diacylglycerol cholinephosphotransferase, were significantly higher in brain microvessels than in aorta in both normotensive and hypertensive rats; lipid hydrolyzing activities, such as lipases and cholesterol esterases, were similar in the two preparations. beta-oxidation in brain microvessels was more active than in aorta in both groups. Hypertension did not alter these enzyme activities in either aorta or brain microvessels, or change beta-oxidation in the aorta. However beta-oxidation in brain microvessels was significantly lower in hypertensive rats than in normotensive rats. These results suggest that brain microvessels are metabolically more active than aorta, and that their beta-oxidation activity is more susceptible to effects of hypertension. Reduced beta-oxidation in brain microvessels might lead to angionecrosis by derangement of energy production, which in turn may cause cerebral bleeding.     

阿托伐他汀对大鼠动脉粥样硬化不稳定斑块内新生血管的影响

目的: 研究阿托伐他汀药物对大鼠动脉粥样硬化斑块内血管生成的影响及可能机制,观察粥样斑块内血管生成与斑块稳定性的关系。方法: 将36只大鼠随机分为正常组,高脂组和阿托伐他汀组。14周后处死大鼠,取血测定血脂及C反应蛋白,观察主动脉病理学变化;测量斑块面积及内膜中膜面积比（I/M）;微血管密度（MVD）测定,免疫组化观察并分析斑块内Ⅷ因子的表达。结果: ①高脂组和阿托伐他汀组血清脂质水平高于正常组（P<0.05）,而二者之间无明显差异性;②高脂组和阿托伐他汀组I/M较正常组明显增多（P<0.05）,而阿托伐他汀组I/M较高脂组明显减少（P<0.05）;③阿托伐他汀和高脂组斑块内MVD及Ⅷ因子阳性率均明显均高于正常组,而阿托伐他汀组MVD及Ⅷ因子阳性率均低于高脂组（P<0.05）;结论: 新生血管多发生在不稳定斑块内,斑块内血管生成是增加斑块不稳定性的又一因素,阿托伐他汀可以减少斑块内血管生成,达到稳定斑块的作用。     

柚皮素脂质体对非酒精性脂肪性肝病大鼠脂质代谢的影响及机制研究

目的 研究柚皮素脂质体对高糖高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)大鼠脂质代谢的影响及其机制。方法 将50只SD大鼠随机分为对照组、模型组、柚皮素组、柚皮素脂质体Ⅰ组和柚皮素脂质体Ⅱ组。除对照组大鼠外,其余四组大鼠均采用高糖高脂饲料饲养建立模型,并分别给予生理盐水、柚皮素30 mg·kg^-1·d^-1、柚皮素脂质体20 mg·kg^-1·d^-1和柚皮素脂质体30 mg·kg^-1·d^-1腹腔注射,观察12 w。采用ELISA法检测血清超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和丙二醛(MDA)水平,采用Western blot法检测肝组织Nrf2蛋白表达,采用RT-PCR法检测肝组织Nrf2 mRNA水平。结果 模型组大鼠体质量、肝质量、血清TC、TG、ALT、AST、SOD、CAT和MDA水平分别为(547.6±19.8)g、(12.9±0.3)g、(1.2±0.2)mmol/L、(2.6±0.2)mmol/L、(69.8±5.3)U/L、(229.6±18.2)U/L、(29.9±6.4)U/L、(26.5±2.4)U/mg和(11.7±1.1)nmol/mL,而柚皮素组、柚皮素脂质体Ⅰ组和柚皮素脂质体Ⅱ组大鼠上述大部分指标均有不同程度的下降(P＜0.05),仅SOD和CAT水平显著升高(P＜0.05);柚皮素组、柚皮素脂质体Ⅰ组和柚皮素脂质体Ⅱ组大鼠肝组织Nrf2蛋白表达和Nrf2 mRNA水平均显著高于模型组。结论 柚皮素脂质体可有效降低NAFLD大鼠血脂水平,促进SOD和CAT生成,其机制可能与激活Nrf2有关。     

健脾疏肝方对非酒精性脂肪性肝炎大鼠肝脂代谢分子网络的影响

目的:观察健脾疏肝方对非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)的疗效以及对NASH大鼠肝脂代谢分子网络的影响.方法:将40只♂SD大鼠随机分成空白组、模型组、健脾疏肝方组、易善复组4组,采用高脂饲料造模连续8wk.模型成立后,改用普通饲料饲喂,同时健脾疏肝方组及易善复组分别予健脾疏肝方浸膏和易善复混悬液灌胃,模型组和空白组予去离子水灌胃,连续4wk;实验结束后处死全部大鼠,观察大鼠肝组织病理改变,测定大鼠肝功、血脂、肝脂以及抗氧化指标水平,观察大鼠肝组织SREBP-1c、SCAP、PPAR、PGC-1、LXR mRNA表达.结果:健脾疏肝方可有效改善大鼠肝组织脂肪变性及炎症损伤,降低肝功、血脂、肝脂水平,提高抗氧化物质,并可同时上调PPAR及PGC-1,下调SREBP-1c及SCAP mRNA表达(P<0.05,P<0.01),且在改善大鼠肝指数、体质量,降低谷丙转氨酶(ALT)水平、肝甘油三酯(TG)、MDA含量,提高GSH-PX含量,上调PPAR、PGC-1mRNA表达等方面优于易善复(P<0.05,P<0.01).结论:健脾疏肝方可通过网络调控NASH肝脂代谢而防治NASH,在今后研究中,可将健脾疏肝方作为基础,结合其他治法,辨证施治.     

Effect of growth hormone administration to hypophysectomized rats on muscle lipid metabolism.

This study was undertaken to determine whether increased oxidation of intracellular muscle lipids could explain the impaired carbohydrate metabolism of that tissue following growth hormone (GH) administration. Pieces of diaphragm from either hypophysectomized (hypox) rats injected for 10 days with saline or 1 mg bovine GH or animals of similar weight with intact pituitary glands were studied. In hypox rats, GH administration increased both weight gain and plasma glucose concentrations at sacrifice and impaired glucose uptake by diaphragms in vitro. Tissue triglyceride (TG) content was markedly decreased in hypox muscle compared to diaphragms removed from animals with intact pituitary glands. GH administration lowered TG levels even further. Initial phospholipid (PL) content was similar in all groups and fell significantly during the second hour of incubation only in hypox muscle. GH administration had no effect on PL changes. The differences in TG- and PL-specific activities strongly suggested that most of the C¹⁴O₂ produced in the second hour of incubation was derived from TG. Approximately 25% of diaphragm TG was oxidized to CO₂ in all three groups of animals. Changes in lipid-specific activities during the second hour indicated that in tissue from hypox animals, TG-fatty acids were converted to PL-fatty acids, whereas no such exchange occurred in muscle from intact rats. In conclusion: (1) enhanced oxidation of intracellular muscle lipids does not explain the effect of GH on carbohydrate metabolism; (2) diaphragm TG content is markedly decreased in hypox animals and is not secondary to GH deficiency; (3) diaphragms incubated in vitro will utilize PL for energy only if TG levels are low; and (4) as PI content falls, some TG-fatty acids are shifted into PL, possibly in an attempt to maintain the important “structural-functional elements” of muscle.     

脂质代谢水平与冠状动脉粥样硬化病变的关系

目的 探讨脂质代谢水平与冠状动脉粥样硬化病变的关系.方法 回顾性分析182 例疑似冠状动脉粥样硬化病变患者的资料,均实施冠状动脉数字减影血管造影(DSA)检查,将有冠状动脉粥样硬化病变者列为研究组,否则列为对照组.检测受试者血浆甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LD...     

三基因突变小鼠血脂代谢及动脉粥样硬化早期病变特征

目的研究血脂代谢相关基因与瘦素受体基因联合突变导致小鼠血脂代谢紊乱的发生机制和动脉粥样硬化早期病变的特点及两者间的关系。方法应用生物化学及组织形态学手段对三基因突变(apoE-/-/LDLR-/-/Leprdb/db)与双基因突变(apoE-/-/LDLR-/-)小鼠和单基因突变(Leprdb/db)小鼠之间血脂及动脉粥样硬化早期病变的差异进行了比较研究。结果三基因突变小鼠3周龄时血浆总胆固醇、甘油三酯和血糖浓度分别为(1988±190)、(293±029)和(727±088)mmol/L,均高于双基因和单基因突变小鼠,同时出现轻微的主动脉内膜损伤,血脂及动脉粥样硬化程度随年龄增长而加重。11周龄三基因突变小鼠血浆总胆固醇、甘油三酯和血糖水平分别高出双基因突变小鼠166、141和24倍,且动脉内膜病变较双基因和单基因突变小鼠明显,其严重程度与血脂紊乱正相关。结论三个脂代谢相关基因联合突变在导致小鼠血脂代谢紊乱及主动脉粥样硬化病变的发生发展中起重要作用。     

有机铬对实验性糖尿病大鼠糖、脂质代谢的影响

目的:观察微量元素铬对实验性糖尿病大鼠糖、脂质代谢的影响。方法;对四氧嘧啶诱导的糖尿病大鼠经灌胃给予有机铬(吡啶甲酸铬)水溶液治疗84天后,用葡萄糖氧化酶法分别观察口服有机铬200μg/d及400μg/d的糖尿病大鼠血糖水平;用酶法测定甘油三酯和胆固醇水平。实验分为4组:1组为正常对照组;2组为铬400μg/d治疗组:3组为铬200μg/d治疗组:4组为糖尿病模型对照组。4组均自由进食。结果:有机铬具有明显的降低血糖、血清甘油三酯和血清胆固醇水平的作用(P<0.05～<0.001)。结论:铬能明显改善糖尿病大鼠的糖、脂代谢。