非诺贝特酯对非酒精性脂肪肝大鼠模型的影响

目的 探讨非诺贝特酯对非酒精性脂肪肝大鼠模型的影响.方法 用高脂乳液制造SD非酒精性脂肪肝大鼠模型,进行随机划分三组,分别是非诺贝特酯组、对照组、易善复组,进行8周治疗后,检测肝组织生化反应和病理学研究.结果 非诺贝特酯对非酒精性脂肪肝大鼠模型的肝脂水平有明显降低的作用,使脂肪变性得到改善.结论 非诺贝特酯对非酒精性脂肪肝大鼠治疗作用明显.     

布渣叶水煎液对非酒精性脂肪肝大鼠促肝纤维化因子的作用研究

目的:观察布渣叶水煎液对非酒精性脂肪肝大鼠血脂、促肝纤维化因子的影响。方法:采用高脂饮食法制备非酒精性脂肪肝大鼠模型;将48只Wistar雄性大鼠随机分为4组:正常对照组、模型对照组、非诺贝特组、布渣叶水煎液组;检测各组大鼠血清和肝组织TC、TG及肝指数变化,检测血清HA、PⅢP和MMP-9等促肝纤维化因子水平。结果:布渣叶水煎液可降低非酒精性脂肪肝大鼠血清和肝组织TC、TG及肝指数,并降低血清促肝纤维化因子水平。结论:布渣叶水煎液对非酒精性脂肪肝大鼠血脂、促肝纤维化因子具有改善作用。     

非酒精性脂肪肝行非诺贝特治疗的临床价值分析

目的:研究分析非诺贝特治疗非酒精性脂肪肝的临床效果。方法:选取我院于2012年4月~2013年5月收治的62例非酒精性脂肪肝患者,将其随机划分为两组,对照组33例患者接受硫普罗宁肠溶片治疗,治疗组29例患者接受非诺贝特治疗,对比两组患者的临床治疗效果。结果:两组患者实施治疗后,治疗组的治疗总有效率为82.8%,对照组的治疗总有效率为69.7%,两组患者的治疗总有效率对比差异显著,对比有统计学意义(P<0.05)。结论:采用非诺贝特对非酒精性脂肪肝进行治疗,其治疗效果显著优于硫普罗宁肠溶片的治疗效果,可显著改善患者的临床症状,提高患者生命质量,值得在临床医学中推广应用。     

非诺贝特和辛伐他汀对酒精性脂肪肝血清游离脂肪酸谱的影响

目的　研究非诺贝特和辛伐他汀对酒精性脂肪肝大鼠模型血清游离脂肪酸谱的影响。方法　以酒精灌胃加橄榄油饮食的方法建立酒精性脂肪肝大鼠模型 ,模型组分为非诺贝特治疗组 (80mg·kg-1)、辛伐他汀治疗组 (4mg·kg-1)以及未治疗组。 4wk后处死大鼠 ,用气相色谱方法测定血清游离脂肪酸谱。结果　非诺贝特治疗组明显改善由乙醇引起的血清多不饱和脂肪酸的降低 [油酸 :(38 2 12± 7 788) μg·L-1vs (31 6 2 0± 6 14 2 ) μg·L-1,亚油酸 :(37 2 6 9± 8 0 6 5 ) μg·L-1vs (30 2 5 4± 9 0 6 3) μg·L-1,花生四烯酸 :(11 6 4 6±2 6 0 1) μg·L-1vs (9 0 12± 1 2 36 ) μg·L-1) ;同时肝脏病理改善。辛伐他汀治疗组则加重血清多不饱和脂肪酸的降低 ,并使饱和脂肪酸增加。结论　非诺贝特和辛伐他汀对酒精性脂肪肝血清游离脂肪酸谱作用不同 ;血清多不饱和脂肪酸在酒精性脂肪肝的发病机制以及治疗反应中可能起着重要的作用     

非诺贝特与多烯磷脂酰胆碱治疗非酒精性脂肪肝效果比较

目的 比较非诺贝特与多烯磷脂酰胆碱治疗非酒精性脂肪肝(NAFLD)的临床疗效.方法 将86例非酒精性脂肪肝患者随机分为治疗组(45例)和对照组(41例).治疗组给予非诺贝特0.2g,每天1次,对照组给予多烯磷脂酰胆碱(易善复)456 mg,每天3次,疗程均为12周.观察两组患者治疗前后的肝功能、血脂、临床症状及肝脏B超检查结果变化,比较两组的疗效.结果 治疗组症状改善率、肝功能及血脂复常率、肝脏超声影像学改善明显优于对照组.治疗组与对照组有效率分别为82.2％( 37/45)、63.4％( 26/41),差异有统计学意义(x2=3.874,P＜0.05).结论 非诺贝特治疗非酒精性脂肪肝疗效好,且药品费用较低,无明显不良反应,值得推广应用.     

当归注射液治疗大鼠非酒精性脂肪肝的实验研究

目的：研究当归注射液对大鼠非酒精性脂肪肝的保护作用。方法：30只Wistar大鼠随机分为对照组、非酒精性脂肪肝模型组和当归治疗组。模型组与治疗组大鼠皮下注射四氯化碳与植物油混合液,3周末停止皮下注射,治疗组开始每日灌胃25%当归注射液10mg（/kg·d）;模型组与对照组均每日灌胃相应剂量生理盐水,持续4周。实验结束处死大鼠,收集血清和肝组织。检测血清ALT、AST、TC、TG、IL-6、TNF-α、瘦素,计算肝指数。结果：与模型组比较,治疗组能显著降低ALT、AST、TC、TG、IL-6、TNF-α、瘦素含量,明显减轻大鼠肝内脂肪沉积。结论：当归注射液治疗非酒精性脂肪肝有效。     

左卡尼汀治疗非酒精性脂肪肝79例临床观察分析

目的:观察左卡尼汀治疗非酒精性脂肪肝的效果.方法:79人被随机分入左卡尼汀组(应用左卡尼汀治疗4周,减量后继续治疗4周),而78人以非诺贝特片剂口服治疗作为对照组.结果:应用左卡尼汀治疗非酒精性脂肪肝79例,显效64例(81.0%),有效9例(11.4%),总有效率为92.4%,无效6例(7.6%),效果明显优于非诺贝特.结论:左卡尼汀治疗非酒精性脂肪肝有一定效果,且不良反应低,值得推广.     

非诺贝特对非酒精性脂肪性肝病疗效观察

目的探讨非诺贝特对非酒精性脂肪性肝病的临床疗效。方法选择河南省驻马店市第二人民医院2006-01-2009-01门诊或住院患者96例非酒精性脂肪性肝病,随机分为两组,分别给予非诺贝特100 mg,3次/d和藻酸双酯钠100 mg,3次/d,口服,疗程4个月,于治疗前后用B型超声波检查肝脏情况。结果非诺贝特组脂肪肝恢复状况显著高于藻酸双酯钠组,总有效率分别为93.8%和75.0%（P〈0.05）。结论非诺贝特对非酒精性脂肪性肝病较藻酸双酯钠有更好的疗效。     

非诺贝特降低生活方式干预无效的脂肪肝患者LDL的疗效

目的调查单用生活方式干预治疗与同时口服非诺贝特治疗非酒精性脂肪肝患者脂代谢紊乱的疗效。方法纳入经6个月的生活方式干预治疗后仍具有脂代谢紊乱的非酒精性脂肪肝患者,口服非诺贝特每日100mg,同时继续进行生活方式干预治疗。结果在52例参加了6个月的生活方式干预治疗的非酒精性脂肪肝患者中,21例仍有脂代谢紊乱的患者被纳入临床研究。纳入患者年龄58(27~75)岁,体质量63.0(39.4~109.0)kg,体质量指数25.4(18.2~37.1)kg·m-2,ALT 23(14~73)IU·L-1,TG 105(92~216)mg·dL-1,HDL 58(37~93)mg·dL-1,LDL 153(66~209)mg·dL-1。21例患者在使用非诺贝特治疗6月后,20例患者中15例(15/20,75%,P=0.001 5)血LDL水平得到改善,5例患者血LDL水平未见明显下降。1例患者口服非诺贝特后出现皮肤瘙痒及皮疹,退出了研究。结论对伴脂代谢紊乱的非酒精性脂肪肝患者,经生活方式干预治疗后脂代谢紊乱未见改善,在联合使用降血脂药物非诺贝特后,脂代谢紊乱可得到改善。     

非诺贝特通过介导TGF-β1/Smad3信号通路对糖尿病肾病大鼠肾功能的保护作用研究

目的 研究非诺贝特保护糖尿病肾病(DN)大鼠肾功能的作用机制.方法 将30只4周龄SD大鼠分为正常对照组、模型组和非诺贝特组,模型组和非诺贝特组大鼠经高糖高脂饲料饲养联合链脲佐菌素腹腔注射构建DN大鼠模型,非诺贝特组大鼠给予非诺贝特50 mg/kg腹腔注射,连续干预8周.干预8周后检测各组大鼠血脂、肾功能指标水平,取肾...     

非诺贝特在非酒精性脂肪性肝病大鼠中的作用探讨

目的高脂饮食构建NAFLD大鼠模型,观察非诺贝特对NFALD大鼠血清学肝功、血脂及肝脏病理的影响。方法将27只雄性SD大鼠随机分为正常组(N组)、病理组(B组)及非诺贝特组(F组),每组9只,分别予正常饮食及高脂饮食建立NAFLD模型。于4、8、12周后,每组各处死大鼠3只,称体重、肝湿重,计算肝指数;8周后测定血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、三酰甘油(TG)、总胆固醇(TC);肝脏病理切片行HE染色,观察病理改变。F组第5周开始药物干预。结果 8周时B组大鼠体重及肝指数高于N组,差异有统计学意义(P<0.05),F组肝指数低于B组,差异有统计学意义(P<0.05);12周时N组与F组大鼠肝指数组间比较差异无统计学意义(P>0.05),B组大鼠体重和肝指数大于N组,差异有统计学意义(P<0.05)。血清学指标:8周时N组与F组AST、ALT、TG、TC比较差异无统计学意义(P>0.05),B组AST、ALT、TG、TC明显高于N组,且差异有统计学意义(P<0.05)。12周时B组AST、ALT、TG、TC明显高于N组,差异有统计学意义(P<0.05),B组ALT、TG高于F组,差异有统计学意义(P<0.05),F组与N组AST、ALT、TC、TG差异无统计学意义(P>0.05)。结论改良法高脂饮食诱导SD大鼠非酒精性脂肪性肝病,造模成功;非诺贝特对NAFLD大鼠的肝脏酶学、血脂及病理学均有一定改善。     

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.     

亚虎四君汤治疗非酒精性脂肪肝的实验研究分析

目的探讨亚虎四君汤防治非酒精性脂肪肝炎（NAFLD）的疗效和作用机制。方法应用高脂饲料饮食制备非酒精性脂肪性肝病动物模型,治疗组药物灌胃,60只清洁小鼠随机分4组：①正常对照组（n=15）普通饲料喂养;②模型组（n=15）高脂饲料喂养;③亚虎四君汤组（n=15）在高脂饲料喂养2周后予亚虎四君汤22g（0．5ml）·d^-1;④非诺贝特阳性对照组（n=15）在高脂饲料喂养2周后予非诺贝特胶囊水溶液22g（0．5ml）·d^-1。观察小鼠一般情况、测定肝指数、血清肝功能、血脂。结果与模型组及对照组相比,亚虎四君汤组的体重、血CHOL（总胆固醇）和血清转氨酶均呈下降趋势。肉眼观察示亚虎四君汤组肝脏组织外形及色泽有明显改善。结论亚虎四君汤在一定程度上有防治NAFLD的作用,作用机制与其能降低血糖,减少脂质瘀积,抑制致炎细胞因子的表达,减少干细胞的变性坏死有关。     

Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome: a randomised study

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS). There is no established treatment for NAFLD. AIM: To evaluate a multifactorial intervention in the treatment of NAFLD. METHODS: A prospective, open-label, randomised study in non-diabetic patients (n = 186) with MetS (follow-up: 54 weeks). All patients had both biochemical and ultrasonographic evidence of NAFLD at baseline. Other causes of liver disease were excluded. Patients received lifestyle advice and treatment for hypertension (mainly inhibitors of the renin-angiotensin system), impaired fasting glucose (metformin), obesity (orlistat) and dyslipidaemia [randomly allocated to atorvastatin 20 mg/day (n = 63) or micronised fenofibrate 200 mg/day (n = 62) or both drugs (n = 61)]. Liver ultrasonography was assessed at baseline and at the end of the study. RESULTS: At the end of treatment, 67% of patients on atorvastatin, 42% on fenofibrate and 70% on combination treatment no longer had biochemical plus ultrasonographic evidence of NAFLD (p < 0.05 vs. baseline for all comparisons). The percentage of patients who no longer had evidence of NAFLD was significantly higher (p < 0.009) in the atorvastatin and combination groups compared with the fenofibrate group. This effect was independently related to drug treatment, as well as to reductions in high-sensitivity C-reactive protein, waist circumference, body weight, triglycerides, low-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure and glucose. Four patients discontinued treatment because of adverse effects. CONCLUSIONS: Multifactorial intervention in MetS patients with both biochemical and ultrasonographic evidence of NAFLD offsets surrogate markers of NAFLD (i.e. elevated aminotransferase plus echogenic liver).     

头顶一颗珠水提取物对非酒精性脂肪肝大鼠肝脏结构及功能的影响

目的：探讨头顶一颗珠对非酒精性脂肪肝（NAFLD）大鼠肝脏结构及功能的影响,阐明头顶一颗珠干预NAFLD的作用机制。方法：采用复合高脂饮食结合四氯化碳溶液腹腔注射建立NAFLD大鼠模型,模型复制成功后动物随机分为正常组、模型组、头顶一颗珠水提取物高、中、低剂量组、多烯磷脂酰胆碱组,连续灌胃给药4周,实验前及实验过程中每周称取大鼠体质量1次,实验结束称取肝湿重,计算肝指数,并观察动物肝脏的质地弹性及颜色、形态等,全自动生化分析仪测定肝酶谱,HE染色行大鼠肝脏病理组织学观察,免疫组化（SP）法检测GRP94蛋白表达,RT-PCR（逆转录聚合酶链反应）法检测GRP94 mRNA基因表达。结果：与正常组比较,模型组大鼠肝脏形态,光镜下结构,体质量、肝湿重和肝指数,肝酶谱,内质网应激等相关指标有显著异常的变化;与模型组比较,头顶一颗珠水提取物各剂量组大鼠肝脏肉眼形态,肝脏病理组织学不同程度改善,ALT、AST、ALP等肝酶谱指标及肝组织GRP94蛋白及基因表达不同程度下降,差异均有统计学意义（P<0.05或P<0.01）;结论：头顶一颗珠水提取物治疗NAFLD疗效明显,可有效逆转肝损伤,从多个层次防治NAFLD。     

甘草酸二铵脂质复合物对大鼠非酒精性脂肪肝的治疗效果研究

目的:研究甘草酸二铵脂质复合物(甘平,DGLL)对大鼠非酒精性脂肪肝(NAFLD)的治疗作用。方法:以高脂饲料喂养方式建立大鼠非酒精性脂肪肝模型,证实造模成功后随机分为空白对照组、模型组、多烯磷脂酰胆碱组和甘平高中低(900、300、100mg/kg)剂量组。给药4周后,处死所有动物,检测血脂、氧化应激、肝功能、胰岛素相关等指标,并观察肝脏组织病理学变化。结果:甘平能显著降低NAFLD大鼠的转氨酶(ALT、AST)活力、丙二醛(MDA)含量、TNF-α水平、空腹血糖(FBG)、空腹胰岛素(FINS)水平和空腹胰岛素抵抗指数(HOMA-IR),升高超氧化物歧化酶(SOD)活力,改善NAFLD大鼠的总胆固醇(TC)、甘油三酯(TG)水平。结论:甘平可以用来治疗大鼠NAFLD,其机制可能与抗氧化作用及改善胰岛素抵抗有关。     

药物对非酒精性脂肪肝大鼠的实验研究

目的观察药物对非酒精性脂肪肝大鼠血浆和肝组织血栓素B2(TXB2)和6-酮-前列腺素F1α(6-Keto-PGFlα)的影响。方法高脂饲料制备Wistar大鼠非酒精性脂肪肝大鼠模型并用降脂益肝冲剂进行干预。苏木素-伊红(HE)染色观察肝脏病理组织学改变,放射免疫法测定血浆和肝组织TXB2和6-Keto-PGFlα含量及其比值。结果治疗组肝脏脂肪变性程度明显改善,6-Keto-PGFlα含量显著高于模型组(P<0.01),TXB2含量、TXB2/6-Keto-PGFlα比值明显低于模型组(P<0.01)。结论降脂益肝冲剂对大鼠血浆和肝组织TXB2、6-Keto-PGFlα的含量及其比值具有调节作用,这可能是其抗非酒精性脂肪肝的作用机制之一。     

非诺贝特对衰老大鼠肝脏组织酰基辅酶A合成酶的影响

摘要目的观察非诺贝特对衰老大鼠肝脏组织酰基辅酶A（CoA）合成酶的影响,探讨衰老后出现脂质代谢异常的可能机制及非诺贝特对脂质代谢的调节作用。方法 雄性SD年轻大鼠（4～6周龄）和老年大鼠（24个月龄）各16只,随机分为对照组（常规喂养2周）和实验组（非诺贝特喂养2周）,测定大鼠血清三酰甘油和总胆固醇水平,采用半定量逆转录聚合酶链反应法检测大鼠肝脏组织酰基CoA合成酶水平。结果与年轻对照组比较,老年对照组三酰甘油和总胆固醇水平升高,老年大鼠肝脏组织酰基CoA合成酶水平表达降低。实验组与老年对照组比较三酰甘油和总胆固醇水平均下降;肝脏组织酰基CoA合成酶水平均升高。结论老年大鼠肝脏组织酰基CoA合成酶水平表达减少可能与老年脂质代谢异常有关;非诺贝特对老年脂质代谢异常有调节作用。     

降脂益肝冲剂对非酒精性脂肪性肝病大鼠肝脏TBP-2mRNA表达的影响

目的 探讨硫氧还蛋白结合蛋白(TBP-2)与大鼠非酒精性脂肪性肝(NAFLD)的关系,并观察降脂益肝冲剂的疗效,探讨其对肝组织TBP-2 mRNA表达的影响.方法 72只雄性Wistar大鼠随机分为9组:空白对照组(N组)、实验对照组(M组),实验干预组(D组),每组24只,分别设9、13、17周三个时相点.空白对照组给予普通饲料喂养,实验对照组和实验干预组给予高脂饮食喂养.实验干预组分别于0周、9周、13周末开始给予降脂益肝冲剂,同时空白对照组和实验对照组分别给予等量的生活饮用水灌胃,分别于9周、13周、17周末处死各组大鼠.应用半定量逆转录-聚合酶链反应(RT-PCR)法测定各组大鼠肝细胞硫氧还蛋白结合蛋白(TBP-2)mRNA的表达;HE染色观察肝组织病理变化.结果 RT-PCR结果发现在单纯性非酒精性脂肪肝期(M1组)TBP-2的mRNA表达(0.63±0.12)较N1组(1.02±0.10)下降明显(P<0.01),可能为机体的一种保护性应激,以减少TBP-2对Trx的抑制作用,间接增加了机体的抗氧化能力.当疾病继续进展到非酒精性脂肪性肝炎期(M2组和M3组),这种保护性应激能力逐渐减少,TBP-2的mRNA表达增加,但仍然少于同期的正常组即空白对照组(N2,N3)(P<0.01),提示机体仍可通过下调TBP-2的表达以增加了机体的抗氧化能力;N1,N2,N3组相比TBP-2的mRNA表达统计学上无差异;D2组(0.66±0.79)与M2组(0.89±0.10),D3组(0.73±0.12)与M3组(0.90±0.88)相比TBP-2的mRNA表达均有所下降(P<0.01).药物干预后,肝脏病理改变较实验对照组明显减轻(P<0.01).结论 TBP-2在单纯性非酒精性脂肪性肝和非酒精性脂肪性肝炎期表达下调,可能是机体的一种保护性应激,参与NAFLD的发生、发展.降脂益肝冲剂对NASLD有很好的防治作用,TBP-2是其可能的作用靶点.     

Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome: a randomised study

ABSTRACT

Background: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS). There is no established treatment for NAFLD.

Aim: To evaluate a multifactorial intervention in the treatment of NAFLD.

Methods: A prospective, open-label, randomised study in non-diabetic patients (n = 186) with MetS (follow-up: 54 weeks). All patients had both biochemical and ultrasonographic evidence of NAFLD at baseline. Other causes of liver disease were excluded. Patients received lifestyle advice and treatment for hypertension (mainly inhibitors of the renin–angiotensin system), impaired fasting glucose (metformin), obesity (orlistat) and dyslipidaemia [randomly allocated to atorvastatin 20?mg/day (n = 63) or micronised fenofibrate 200?mg/day (n = 62) or both drugs (n = 61)]. Liver ultrasonography was assessed at baseline and at the end of the study.

Results: At the end of treatment, 67% of patients on atorvastatin, 42% on fenofibrate and 70% on combination treatment no longer had biochemical plus ultrasonographic evidence of NAFLD (?p < 0.05 vs. baseline for all comparisons). The percentage of patients who no longer had evidence of NAFLD was significantly higher (?p < 0.009) in the atorvastatin and combination groups compared with the fenofibrate group. This effect was independently related to drug treatment, as well as to reductions in high-sensitivity C-reactive protein, waist circumference, body weight, triglycerides, low-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure and glucose. Four patients discontinued treatment because of adverse effects.

Conclusions: Multifactorial intervention in MetS patients with both biochemical and ultrasonographic evidence of NAFLD offsets surrogate markers of NAFLD (i.e. elevated aminotransferase plus echogenic liver).