Pentoxifylline alleviates high-fat diet-induced non-alcoholic steatohepatitis and early atherosclerosis in rats by inhibiting AGE and RAGE expression

Aim:

To investigate the expression of advanced glycation end products (AGEs) and their receptor RAGE in the livers and blood vessels of rats with non-alcoholic steatohepatitis (NASH) and the effect of pentoxifylline (PTX) on liver and artery function in rats with NASH.

Methods:

Sprague-Dawley rats were fed a high-fat diet for 12 weeks and given PTX by gavage for 4 weeks. The effects of PTX on hepatic liver and vessel function as well as the expression of AGE and RAGE in rats with NASH were assessed. The intima-media thickness (IMT) of the aorta and carotid artery was evaluated using ultrasonography.

Results:

Serum aspartic aminotransferase (AST) and blood levels of glucose (GLU) were reduced in the PTX group relative to the NASH group. The IMT of the aorta and carotid artery was increased in the NASH group compared with the control group. The IMT was reduced in NASH rats after treatment with PTX. Rats with NASH demonstrated higher AGE and RAGE protein levels in the liver and arteries compared with those of control rats. PTX treatment in NASH rats resulted in a decrease in AGE and RAGE protein levels in the liver and arteries compared with those in the NASH group.

Conclusion:

Early atherosclerosis was observed in rats with NASH induced by a 16-week high-fat diet. High expression of AGE and RAGE in the livers and arteries of rats with NASH may contribute to the pathogenesis of NASH and early atherosclerosis. PTX showed protective effects on hepatic and arterial function, partially through inhibition of AGE and RAGE expression.     

Knockdown of hepatic aquaglyceroporin-9 alleviates high fat diet-induced non-alcoholic fatty liver disease in rats

Non-alcoholic fatty liver disease (NAFLD) has emerged as a common public health problem that can progress to end-stage liver disease. Although the function of aquaglyceroporin-9 (AQP9) as a glycerol channel has been proven, the mechanism of AQP9 in the development of NAFLD is poorly understood. To investigate the effect of hepatic glycerol uptake inhibition, we utilized a lentivirus-associated RNA interference technique to knock down the expression of hepatic AQP9 in high fat diet (HFD)-induced NAFLD in rodents. Male Sprague–Dawley rats were fed with a standard chow diet or HFD for 8 weeks. Rats fed a HFD were separated into 3 groups: HFD, control and transfection group, which were injected with equivalent amounts of PBS, lentivirus-scramble and lentivirus-shRNA-AQP9 through the hepatic portal vein. The results showed a remarkable decrease in the expression of AQP9 mRNA and protein in liver for the transfection group. Furthermore, less hepatic steatosis occurred when compared to the HFD and control groups after 8 weeks. Our results indicate a potential role for AQP9 in the pathogenesis of hepatic steatosis.     

Effects of fenofibrate and xuezhikang on high-fat diet-induced non-alcoholic fatty liver disease

1. Fenofibrate and xuezhikang are two types of drugs widely used in the treatment of dyslipidaemia in China. The main purpose of present study was to test the efficacies and explore the potential mechanisms of action of the two lipid-lowering agents on high-fat diet-induced non-alcoholic fatty liver disease (NAFLD). 2. Rats were randomly divided into four groups, with eight rats per group. One group was given normal diet, whereas the other three groups were fed a high-fat diet. Forty-two days later, two of the high-fat diet-fed groups were administered fenofibrate (100 mg/kg, p.o.) and xuezhikang (300 mg/kg, p.o.) for another 42 consecutive days. The other two groups were administered placebo (saline) by gavage. 3. Typical pathological symptoms of NAFLD occurred in the high-fat diet groups. Fenofibrate and xuezhikang treatment markedly improved NAFLD, ameliorating dyslipidaemia and fat accumulation in the liver, improving insulin resistance and ameliorating oxidative stress. Hepatic steatosis, necro-inflammation and collagen deposition were lessened in the drug-treated groups. However, both xuezhikang and fenofibrate failed to reverse hepatomegaly and fenofibrate even aggravated it. Xuezhikang reversed aminotransferase abnormalities, but fenofibrate had less of an effect. 4. The common therapeutic mechanism of action of fenofibate and xuezhikang likely involves inhibition of the hepatic expression of tumour necrosis factor-alpha. Fenofibrate upregulated mRNA levels of peroxisome proliferator-activated receptor (PPAR) alpha in the liver, whereas xuezhikang had no effect on the hepatic expression of PPARalpha and this may explain, in part, their different effects on the NAFLD rats. 5. The results suggest that fenofibrate and xuezhikang may have potential clinical application in the treatment of NAFLD. However, the side-effects of fenofibrate and the underlying constituents of xuezhikang need to be determined and investigated further.     

Ezetimibe improves high fat and cholesterol diet-induced non-alcoholic fatty liver disease in mice

Ezetimibe is a novel cholesterol and plant sterol absorption inhibitor that reduces plasma low-density lipoprotein-cholesterol by selectively binding to the intestinal cholesterol transporter, Niemann-Pick C1-Like 1. Mice deficient in Niemann-Pick C1-Like 1 are protected from high fat/cholesterol diet-induced fatty liver as well as hypercholesterolemia. The object of the present study was to determine whether ezetimibe treatment could reduce hepatic steatosis in diet-induced obese mice. C57BL/6J mice were fed a high fat/cholesterol containing semi-purified diet (45% Kcal fat and 0.12% cholesterol) for 7 months after weaning. These mice were not only obese, but also developed hepatomegaly and hepatic steatosis, with varying degrees of liver fibrosis and steatohepatitis. About 87% of the mice on the high fat/cholesterol diet for 7 months had elevated plasma alanine aminotransferase activity, a biomarker for non-alcoholic fatty liver disease. Chronic administration of ezetimibe for 4 weeks significantly reduced hepatomegaly by decreasing hepatic triglyceride, cholesteryl ester and free cholesterol in diet-induced obese mice fed high fat/cholesterol diet for 7 months. Chronic ezetimibe treatment also significantly decreased plasma alanine aminotransferase activity. These results suggest that ezetimibe may be a novel treatment for high fat/cholesterol-induced non-alcoholic fatty liver disease.     

Cassia tora (Leguminosae) seed extract alleviates high-fat diet-induced nonalcoholic fatty liver

The aim of this study was to examine the effects of Cassia tora seeds on high-fat diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. After being fed a HFD for two weeks, rats were orally dosed with Cassia seed ethanol extract (CSEE) (100, 200, or 300 mg/kg) once daily for 8 weeks. CSEE induced dose-dependent reductions in plasma lipid levels, as well as decreased the over hepatic lipid accumulation. Furthermore, CSEE treatment improved HFD-induced hepatic histological lesions. CSEE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated the gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the livers of HFD-fed rats. AMPK inhibition by compound C retarded CSEE-induced reduction in triglyceride accumulation in HepG2 cells stimulated by insulin. Our findings suggest that CSEE may regulate hepatic lipid homeostasis related with an AMPK-dependent signaling pathway. Targeting AMPK activation with CSEE may represent a promising approach for the prevention and treatment of obesity-related non-alcoholic fatty liver disease.     

机械加载对高脂饮食诱导的肥胖和非酒精性脂肪肝的治疗作用

目的 探讨机械加载对高脂饮食诱导的肥胖和非酒精性脂肪肝的疗效。方法 选用6周龄的C57BL/6雌性小鼠30只,体质量约18 g,按随机数字表法分为正常对照组（NC组）、高脂饮食组（HF组）和高脂饮食机械加载治疗组（HF+L组）,每组10只,持续饮食诱导12周。高脂饮食6周后,HF+L组进行机械加载治疗6周。实验动物进行体成分分析,观测全身体脂含量的变化。收集肾周脂肪、子宫周脂肪、肠系膜脂肪、腹股沟脂肪和肝脏并称量湿质量。留取部分肝脏做组织形态学检测,油红O和HE染色分析观察肝脏的病理改变,部分肝脏用于Western blot检测内质网应激相关蛋白（eIF2α、p-eIF2α、ATF4）的表达。结果 与NC组相比,高脂饮食导致HF组体质量、体脂明显增加,机械加载治疗后,HF+L组体质量、体脂较HF组明显降低（P＜0.05）。肝脏组织学结果表明,高脂饮食导致一定程度的肝脏脂肪变性,通过治疗后,脂肪变性得到有效缓解（P＜0.05）。Western blot分析结果表明,高脂饮食导致小鼠肝脏eIF2α、p-eIF2α和ATF4蛋白表达升高,机械加载能够抑制肝脏p-eIF2α和ATF4蛋白的表达。结论 机械加载能够有效缓解高脂饮食导致的体质量、体脂增加及非酒精性脂肪肝,其治疗作用可能与肝脏内质网应激有关。     

Current best treatment for non-alcoholic fatty liver disease

Treatment of patients with non-alcoholic fatty liver disease (NAFLD) has typically been focused on the management of associated conditions such as obesity, diabetes mellitus and hyperlipidaemia. NAFLD associated with obesity may be resolved by weight reduction, although the benefits of weight loss have been inconsistent. Improving insulin sensitivity with lifestyle modifications or medications usually improves glucose and lipid levels in patients with diabetes and hyperlipidaemia. Improving insulin sensitivity is expected to improve the liver disease but in many diabetic/hyperlipidaemic patients with NAFLD, the appropriate control of glucose and lipid levels is not always accompanied by improvement of the liver condition. Results of pilot studies evaluating ursodeoxycholic acid, gemfibrozil, betaine, N-acetylcysteine, αtocopherol, metformin and thiazolidinedione derivatives suggest that these medications may be of potential benefit. This article reviews the treatment modalities currently available for patients with NAFLD, including emerging data from clinical trials evaluating promising medications as well as possibilities for the future.     

Cold-pressed raspberry seeds oil ameliorates high-fat diet triggered non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is considered one of the most serious public health problems affecting liver. The reported beneficial impact of raspberries on obesity and associated metabolic disorder makes it a suitable candidate against NAFLD. In the current study, the chemical profile of raspberry seed oil (RO) was characterized by analysis of fatty acid and tocopherol contents using high-performance liquid chromatography (HPLC) in addition to the determination of total phenolic and flavonoids. High levels of unsaturated fatty acids, linoleic acid (49.9%), α-linolenic acid (25.98%), and oleic acid (17.6%), along with high total tocopherol content (184 mg/100 gm) were detected in oil. The total phenolic and flavonoid contents in RO were estimated to be 22.40 ± 0.25 mg gallic acid equivalent (GAE)/100 mg oil and 1.34 ± 0.15 mg quercetin (QU)/100 mg, respectively. Anti-NAFLD efficacy of RO at different doses (0.4 and 0.8 mL) in a model of a high-fat diet (HFD) fed rats was assessed by estimating lipid profile, liver enzyme activity, glucose and insulin levels as well as adipokines and inflammatory marker. Peroxisome proliferator-activated receptor γ (PPARγ), which is a molecular target for NAFLD was also tested. Liver histopathology was carried out and its homogenate was used to estimate oxidative stress markers. Consumption of RO significantly improved lipid parameters and hepatic enzyme activities, reduced insulin resistance and glucose levels, significantly ameliorated inflammatory and oxidative stress markers. Furthermore, RO treatment significantly modulated adipokines activities and elevated PPARγ levels. Raspberry seed oil administration significantly improved these HFD induced histopathological alterations. Moreover, a molecular docking study was performed on the identified fatty acids and tocopherols. Among the identified compounds, oleic acid, α-linolenic acid and γ-tocopherol exhibited the highest docking score as PPARγ activator posing them as a potential anti-NAFLD drug leads. Study findings suggest RO as an effective therapeutic candidate for ameliorating NAFLD.     

Curcumin decreases oxidative stress in mitochondria isolated from liver and kidneys of high-fat diet-induced obese mice

Oxidative stress plays a key role in obesity and diabetes-related mitochondrial dysfunction. Mitochondrial dysfunction is characterized by increased oxidative damage, nitric oxide (NO) synthesis, and a reduced ratio of adenosine-5'-triphosphate (ATP) production/oxygen consumption. Curcumin represents a potential antioxidant and anti-inflammatory agent. In this study, our objective was to determine the effect of curcumin treatment on oxidative stress and mitochondrial dysfunction in high-fat diet (HFD)-induced obese mice (OM). These results suggest that curcumin treatment increased oxygen consumption and significantly decreased lipid and protein oxidation levels in liver mitochondria isolated from HFD-induced OM compared with those in the untreated OM (UOM). In kidney mitochondria, curcumin treatment significantly increased oxygen consumption and decreased lipid and protein peroxidation levels in HFD-induced OM when compared with those in UOM. Curcumin treatment neither has any effect on body weight gain nor have any effects on mitochondrial NO synthesis. These findings suggest that obesity induces oxidative stress and mitochondrial dysfunction, whereas curcumin may have a protective role against obesity-induced oxidative stress and mitochondrial dysfunction.     

The fatty acid oxidation pathway as a therapeutic target for insulin resistance

It is recognised that obesity is a major driver for insulin resistance and Type 2 diabetes in both adult and young members of diverse societies. Weight loss strategies involving diet, exercise and behaviour modification work only for the minority of highly motivated individuals, but fail completely in the vast majority; yet weight loss is associated with benefits in metabolic health. Why is it so difficult to maintain weight loss in the longer term? Here, the authors explore the possibility that energy partitioning, especially of lipids, plays a key role in both weight recidivism and, by association, insulin resistance. Drug targets that address key pathways important in this process, where progress in drug discovery is apparent, are discussed.     

酒精性脂肪肝脂质代谢研究进展

酒精性脂肪肝(AFL)是长期大量饮用酒精引发的肝脏损害性病变,可逆转也可进一步发展为肝纤维化和肝硬化。众多的脂肪细胞因子如瘦素(Leptin)、抵抗素(Resistin)和肿瘤坏死因子-α(TNF-α)在脂肪肝的发病中起到一定的促进作用,脂联素(Adiponectin)能改善脂质代谢,延缓脂肪肝的发生;脂联素通过腺苷酸活化蛋白激酶(AMPK)调节糖脂代谢、改善胰岛素敏感性。脂联素/AMPK信号通路是酒精在肝脏的作用靶点、也是调节PPARγ作用的重要信号通路;脂肪分化相关蛋白(ADRP)调节脂质代谢、促进酒精性脂肪肝的形成;过氧化物酶增殖体激活受体γ(PPARγ)参与机体脂质稳态的调节,脂肪肝时PPARγ表达增高,肝纤维化时PPARγ表达减少。对酒精性脂肪肝脂质代谢的深入研究,有助于阐明酒精性脂肪肝发病机制并为临床防治ALD及脂质代谢相关疾病提供新策略。     

脂多糖加速饮食所致非酒精性脂肪肝小鼠的炎症和氧化应激

目的本研究旨在探讨脂多糖在非酒精性肝炎(NASH)模型中的作用。方法采用胆碱蛋氨酸缺乏(Methionine choline deficient,MCD)饮食诱导的小鼠NASH模型。18只雄性C57BL/6小鼠分为3组,MCS+Saline组给予正常饮食+腹腔生理盐水,MCD+Saline组给予胆碱蛋氨酸缺乏饮食+腹腔注射生理盐水,MCD+LPS组给予胆碱蛋氨酸缺乏饮食+腹腔注射1 mg/kg脂多糖,共2周。在最后一次注射的6 h之后处死小鼠,取血清和肝组织。进行肝脏HE染色和Sirius Red染色,观察肝组织病理学变化。并测定血清中血清丙氨酸氨基转移酶(ALT)和肿瘤坏死因子-α(TNF-α)的含量。结果 MCD造成小鼠肝脏中大量脂肪滴的沉积和炎症细胞浸润,血清ALT升高,脂多糖注射进一步加重肝细胞凋亡,肝脏中TBARS进一步升高,血清TNF-α含量显著增加。结论在MCD所致非酒精性脂肪肝炎模型小鼠中,腹腔注射脂多糖引起血清中TNF-α升高,进一步加重细胞凋亡,因此,脂多糖在非酒精性脂肪肝炎的进程中具有重要作用,提示临床预防或治疗非酒精性脂肪肝炎需要关注患者肠道菌群失调症状。     

Red algae (Gelidium amansii) hot-water extract ameliorates lipid metabolism in hamsters fed a high-fat diet

The purpose of this study was to investigate the effects of Gelidium amansii (GA) hot-water extracts (GHE) on lipid metabolism in hamsters. Six-week-old male Syrian hamsters were used as the experimental animals. Hamsters were divided into four groups: (1) control diet group (CON); (2) high-fat diet group (HF); (3) HF with GHE diet group (HF + GHE); (4) HF with probucol diet group (HF + PO). All groups were fed the experimental diets and drinking water ad libitum for 6 weeks. The results showed that GHE significantly decreased body weight, liver weight, and adipose tissue (perirenal and paraepididymal) weight. The HF diet induced an increase in plasma triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol and very-low-density lipoprotein cholesterol levels. However, GHE supplementation reversed the increase of plasma lipids caused by the HF diet. In addition, GHE increased fecal cholesterol, TG and bile acid excretion. Lower hepatic TC and TG levels were found with GHE treatment. GHE reduced hepatic sterol regulatory element-binding proteins (SREBP) including SREBP 1 and SREBP 2 protein expressions. The phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) protein expression in hamsters was decreased by the HF diet; however, GHE supplementation increased the phosphorylation of AMPK protein expression. Our results suggest that GHE may ameliorate lipid metabolism in hamsters fed a HF diet.     

Fruit vinegars attenuate cardiac injury via anti-inflammatory and anti-adiposity actions in high-fat diet-induced obese rats

Context: Fruit vinegars (FVs) are used in Mediterranean folk medicine for their hypolipidemic and weight-reducing properties.

Objective: To investigate the preventive effects of three types of FV, commonly available in Algeria, namely prickly pear [Opuntia ficus-indica (L.) Mill (Cectaceae)], pomegranate [Punica granatum L. (Punicaceae)], and apple [Malus domestica Borkh. (Rosaceae)], against obesity-induced cardiomyopathy and its underlying mechanisms.

Materials and methods: Seventy-two male Wistar rats were equally divided into 12 groups. The first group served as normal control (distilled water, 7?mL/kg bw), and the remaining groups were respectively treated with distilled water (7?mL/kg bw), acetic acid (0.5% w/v, 7?mL/kg bw) and vinegars of pomegranate, apple or prickly pear (at doses of 3.5, 7 and 14?mL/kg bw, acetic acid content as mentioned above) along with a high-fat diet (HFD). The effects of the oral administration of FV for 18 weeks on the body and visceral adipose tissue (VAT) weights, plasma inflammatory and cardiac enzymes biomarkers, and in heart tissue were evaluated.

Results: Vinegars treatments significantly (p?Discussion and conclusion: These findings suggest that pomegranate, apple and prickly pear vinegars may prevent HFD-induced obesity and obesity-related cardiac complications, and that this prevention may result from the potent anti-inflammatory and anti-adiposity properties of these vinegars.     

Current pharmacotherapy for treating pediatric nonalcoholic fatty liver disease

Introduction: In the past decade, nonalcoholic fatty liver disease (NAFLD) had rapidly become one of the most common liver diseases. If efficient therapeutic strategies will not reduce the prevalence of NAFLD in children soon, serious deleterious effects on the quality of life of these patients in adulthood are expected. Lifestyle modification is the current first-line therapy for pediatric NAFLD, even though it is difficult to obtain and to maintain. Therefore, lifestyle changes are usually ineffective and long-lasting improvement of the NAFLD-associated liver damage is rarely observed. As guidelines for the management of NAFLD in children are still lacking, the identification of effective treatments represents a challenge for pediatric hepatologists in the near future.

Areas covered: Here, we review the existing therapeutic approaches for treating NAFLD in children and overview all ongoing clinical trials for new promising drugs in pediatric setting.

Expert opinion: Considering the multifactorial pathogenesis and the wide spectrum of histological and clinical features of NAFLD, we believe that a drug mix, containing agents that are effective against the principal pathogenetic factors, associated with lifestyle modification, could represent the winning choice of treatment for pediatric NAFLD.     

2-(3,4-Dihydro-2H-pyrrolium-1-yl)-3oxoindan-1-olate (DHPO), a novel, synthetic small molecule that alleviates insulin resistance and lipid abnormalities

Type-2 diabetes is growing at epidemic proportions world-wide. This report describes the effect of a novel, synthetic, small molecule 2-(3,4-dihydro-2H-pyrrolium-1-yl)-3oxoindan-1-olate (DHPO), on metabolic abnormalities in genetic and dietary mouse models of type-2 diabetes. DHPO (20 mg/kg/d i.p. for 21 days) attenuated fasting blood glucose, improved glucose disposal and corrected dyslipidemia in genetic (leptin deficient, ob/ob) and dietary (high-fat-fed) mouse models of insulin resistance. In addition, DHPO augmented 2-deoxy-d-glucose (2DG) uptake in gastrocnemius muscles of wild-type mice and in cultured myotubes. The increase in 2DG-uptake was associated with an increase in the phosphorylation of AMPK (thr-172) and its downstream effector acetyl-CoA carboxylase without any changes in the phosphorylation of Akt of insulin receptor. The AMPK inhibitor, compound C attenuated DHPO-induced glucose-uptake whereas the PI3-kinase inhibitor Wortmannin was less effective. In addition, DHPO failed to augment glucose-uptake in the gastrocnemius muscle from AMPK-α2-transgenic (kinase-dead) mice. Taken together, these results suggest that DHPO is a novel small molecule that alleviates impaired glucose tolerance and lipid abnormalities associated with type-2 diabetes.     

厄贝沙坦对高血压合并糖尿病大鼠脂肪肝的治疗作用及机制探讨#br#

摘要：目的　探讨厄贝沙坦对高血压合并糖尿病（SHDM）大鼠脂肪肝的治疗作用及对过氧化物酶体增殖物激活受体γ（PPAR-γ）介导AMPK/mTOR信号通路的影响。方法　原发性高血压模型大鼠通过链脲佐菌素联合高糖高脂饲料建立SHDM大鼠模型。将模型大鼠随机分为模型组、厄贝沙坦组和厄贝沙坦+PPAR-γ抑制剂组,另设正常对照组。分别干预8周后,观察血压、血糖、血脂、肝功能以及肝脏病理的变化,检测肝组织PPAR-γ、AMPK/mTOR信号通路及自噬标志蛋白LC3B的表达情况,并利用电镜观察肝脏自噬小体的变化。结果　与模型组相比,经厄贝沙坦治疗后,SHDM大鼠收缩压、血糖、血脂、肝功能及肝脏病理脂肪变均明显改善（P＜0.05）;但厄贝沙坦联合PPAR-γ抑制剂干预后,以上指标除血糖外,均再次升高,并且厄贝沙坦增加SHDM大鼠肝组织PPAR-γ表达和AMPK磷酸化水平,降低mTOR磷酸化水平,升高LC3BⅡ/Ⅰ比值和肝细胞自噬小体数量,与模型组相比,其差异均有统计学意义（P＜0.05）。但是,加用PPAR-γ抑制剂后,以上效应被逆转。结论　厄贝沙坦对SHDM大鼠脂肪肝有治疗作用,其作用机制与激活PPAR-γ介导的AMPK/mTOR信号通路,从而促进肝细胞自噬有关。     

阿托伐他汀对高脂饮食大鼠非酒精性脂肪性肝炎的影响

目的观察阿托伐他汀对高脂饮食大鼠非酒精性脂肪性肝炎(NASH)的影响。方法将23只SD大鼠随机分为三组:正常对照组(NC组,8只)、高脂饲养模型组(HF组,7只)和高脂饲养+阿托伐他汀组(HF+AT组,8只)。观察大鼠血清及肝脏各指标的变化,RT-PCR分别检测肝组织核转录因子κB(NF-κB)、肿瘤坏死因子α(TNF-α)及过氧化物酶体增生物激活受体γ(PPARγ)mRNA表达。结果与HF组相比,HF+AT组大鼠血清相关指标明显改善,肝组织脂肪变性及炎症活动得以减轻,肝脏NF-κB及TNF-αmRNA表达降低,PPARγmRNA表达增加(P<0.05或P<0.01)。结论阿托伐他汀能减轻高脂诱导的模型大鼠NASH。     

氢杨梅素改善高脂饮食诱导的肥胖小鼠肝脏脂肪沉积及机制（英文）

有文献报道, SIRT1-AMPK信号通路可能在DHM改善肝脏细胞甘油三酯蓄积、胰岛素抵抗等作用中发挥作用。为此,本课题拟进一步观察DHM对高脂饮食诱导的肥胖小鼠肝脏脂肪沉积的影响,并探讨其可能机制。C57BL/6J小鼠采用普通饲料和高脂饲料喂养,同时分别用或不用低剂量(125 mg/kg)或高剂量(250 mg/kg)的DHM处理16周。实验期间,每两周检测体重一次。16周后,眼眶静脉取血并处死动物,同时取肩胛下、附睾与腹股沟的脂肪并用电子秤进行称重,并记录脂肪重量。全自动生化分析仪检测:血清甘油三酯(triglyceride,TG)、血清总胆固醇(totalcholesterol,TC)、血清高密度脂蛋白(high-densitylipoprotein,HDL)、血清低密度脂蛋白(low-densitylipoprotein,LDL)。取肝脏甲醛固定、HE和油红O染色检测肝脏脂肪沉积情况;比色法检测肝脏MDA和SOD含量; Realtime PCR检测相关指标的基因表达:IL-6、IL-8、TNF-α、乙酰辅酶A羧化酶(acetyl-Co A carboxylase, ACC)、固...