两种调脂药物对高脂血症性脂肪肝治疗的实验性研究.

目的探讨不同作用机制的调脂药(非诺贝特和辛伐他汀)对高脂血症性脂肪肝的作用.方法高脂食饵性喂养诱导大鼠高脂血症性脂肪肝模型.分别给予非诺贝特、辛伐他汀治疗,观察肝指数、肝功能,血脂、肝脂、血清及肝组织过氧化脂质(MDA)含量及组织学的变化.结果非诺贝特显著降低血脂,分别为TC(mmol/L)1.80±0.20与2 10±0.33,TG(mmol/L)0.76±0.18与1.09±0.31、血清及肝组织MDA含量(nmol/ml)分别3.97±0.57与6.89±1.22和75.22±20.88与106.69±15.60,但ALT、ALP、肝脂、肝指数却显著升高,肝组织学呈重度脂肪变;辛伐他汀显著降低血脂、肝脂、血清及肝组织MDA含量,对肝功能无影响,肝组织学接近正常.结论非诺贝特虽可显著降低血脂,但却加重肝内脂质沉积,不宜用于高脂血症性脂肪肝的治疗.辛伐他汀显著降低血脂及肝脂,降低脂质过氧化,,对肝功能无影响,可较安全、有效地用于高脂血症脂肪肝的治疗.     

肝脂复煎剂对实验性脂肪肝的治疗效应

[目的]探讨肝脂复煎剂对实验性脂肪肝的治疗作用.[方法]通过高脂饮食饲养制备大鼠脂肪肝模型;肝脏病理切片证实造模成功.造模大鼠40只随机分为5组,肝脂复低、中、高剂量治疗组,饮食治疗组及模型对照组.分别检测各组大鼠的肝指数(肝重/体重)、肝功能、血脂、血糖、肝脂、血清和肝组织中丙二醛(MDA)及肝组织学改变.[结果]肝脂复煎剂组血脂改善、肝脂显著降低(P＜0.05,＜0.01),血清和肝组织中丙二醛(MDA)显著降低(P＜0.05,＜0.01),肝组织学接近正常.饮食治疗组改善不大.[结论]肝脂复煎剂可有效地用于实验性脂肪肝的治疗.     

健肝消脂合剂对脂肪肝大鼠过氧化物的影响及肝脏病理学改变

[目的]进一步探讨健肝消脂合剂对高脂血症性脂肪肝大鼠肝脏脂变的改善及作用机制。[方法]采用高脂饮食建立营养性脂肪肝大鼠模型,设健肝消脂合剂大、小剂量治疗组和大、小剂量预防组,以东宝肝泰组（简称东宝组）、模型组、正常组为对照组,观察健肝消脂合剂对高脂血症性脂肪肝大鼠血清超氧化物歧化酶（SOD）、丙二醛（MDA）的影响及肝脏病理学的改变。[结果]模型组较正常血清MDA组显著升高,SOD显著降低（P〈0.01）;治疗组、预防组较模型组血清MDA显著降低,SOD升高（均P〈0.01）;模型组大鼠肝脏受损面积明显高于正常组（P〈0.01）;大、小剂量预防组和治疗组均明显低于模型组（P〈0.01）。[结论]健肝消脂合剂能有效地抑制肝细胞内氧应激-脂质过氧化损伤,显著改善脂肪肝病理变化;其作用机制可能通过减少脂质在肝脏沉积与减轻过氧化损伤改善脂肪肝。     

蛇毒类凝血酶对兔高脂血症及脂肪肝的形成的影响

为观察蛇毒类凝血酶对高脂血症及脂肪肝的形成的影响 ,将 2 7只家兔随机分为正常组、模型组和治疗组 ,每组 9只。模型组采用高脂饮食加免疫损伤诱发高脂血症及脂肪肝 ,治疗组给予蛇毒类凝血酶 (1.5u/kg ,连续 3d ,此后每隔 5d 1次 )干预。于实验第 0、15、30、45、6 0及 70d动态观察血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血浆纤维蛋白原和谷丙转氨酶的变化。实验结束时取肝脏标本进行观察 ,检测肝脏脂质含量 ,半定量逆转录聚合酶链反应测定肝组织诱导型一氧化氮合酶mRNA的表达。结果发现 ,模型组血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇和血浆纤维蛋白原进行性升高 ;实验结束时 ,模型组家兔肝脏呈严重脂肪变性 ,肝脏脂质含量明显增高 ,肝组织诱导型一氧化氮合酶mRNA呈高表达 (与正常组相比P <0 .0 1)。与模型组相比 ,治疗组在用药后各时点血浆纤维蛋白原均明显降低 (P <0 .0 5 ) ,但实验后期降纤程度有减弱趋势 ;蛇毒类凝血酶对血脂影响在各时点均无显著性差异 ;肝组织学脂肪变性、肝脏脂质含量及诱导型一氧化氮合酶mRNA表达亦无明显改变。结果提示 ,蛇毒类凝血酶能明显降低家兔高脂饮食诱发的高纤维蛋白原血症 ,但不能抑制高脂血症及脂肪肝的形成。     

阿托伐他汀治疗高脂血症性脂肪性肝炎的实验性研究

目的:探讨阿托伐他汀对高脂血症性脂肪性肝炎大鼠的作用。方法:40只SD大鼠持续10周高脂饮食后随机分为2组:模型组(n=20)和阿托伐他汀组(n=20)均恢复正常饮食。同时给予阿托伐他汀(4 mg/kg·d-1)。另设20只普通饮食大鼠作正常对照。4周后处死,分别测定血清肝功能、甘油三酯(TG)、胆固醇(TC)、游离脂肪酸(FFA)、血浆脂蛋白脂酶(LPL)、肝脂酶(HL),血清及肝组织丙二醛(MDA)、肿瘤坏死因子-α(TNF-α),观察肝脏病理变化。结果:与对照组比较,模型组血脂、ALT、AST、血清及肝组织MDA、TNF-α明显升高,血浆LPL、HL明显下降,病理学检查示明显脂肪性肝炎;与模型组比较,阿托伐他汀组血脂紊乱明显改善,血清ALT、AST、血清及肝组织MDA明显降低,血浆LPI、HL明显升高,病理学检查接近正常,但TNF-α下降不明显。结论:阿托伐他汀可通过减轻脂质过氧化促进肥胖高脂血症性脂肪肝性肝炎的痊愈。     

Bezafibrate对大鼠高脂血症和脂肪肝形成的影响

目的探讨以降低甘油三酯为主的血脂调整药对高脂血症脂肪肝的防治作用。方法观察Ｂｅｚａｆｉｂｒａｔｅ对高脂饮食诱发Ｗｉｓｔａｒ大鼠高脂血症和脂肪肝形成的影响（治疗组,ｎ＝８）,并设模型组和正常饮食组作对照。结果与正常组相比,模型组血脂和肝匀浆脂肪含量均显著升高,肝组织学呈中至重度脂肪变。与模型组相比,治疗组血清甘油三酯和总胆固醇显著下降,但血清转氨酶和肝匀浆脂质含量却呈升高趋势,肝脏病理学变化与模型组基本相近。结论Ｂｅｚａｆｉｂｒａｔｅ虽可显著降低高脂饮食诱发的高脂血症,但对肝内脂肪沉积并无防治作用。     

脂肪肝大鼠线粒体膜流动性改变及活血化瘀法防治的实验研究

目的:探讨脂肪肝大鼠线粒体膜流动性改变及活血化瘀法的防治作用.方法:采用高脂饲料辅以乙醇和CCl4复制脂肪肝大鼠模型,观察大鼠肝脏线粒体膜的流动性,肝组织中SOD、MDA含量及肝脂,血清肝功能,血脂等变化,并以活血化瘀法进行防治,观察其对上述指标的影响.结果:模型组肝线粒体膜流动性、SOD活性明显降低、而肝组织MDA含量、肝脂及血清ALT、AST、TG、TC显著升高,与正常组比较差异有显著性意义(P＜0.01);活血化瘀法能明显改善肝线粒体膜流动性,增强SOD活性,降低血脂、肝脂、MDA含量,改善肝功能(P＜0.05或P＜0.01).结论:脂肪肝大鼠肝脏脂质过氧化增强,线粒体膜流动性降低;活血化瘀法可通过减轻肝脏脂质过氧化并修复线粒体膜流动性,从而达到减轻肝脂变、保护肝功能的作用.     

清肝降浊颗粒对酒精合并高脂饮食性脂肪肝大鼠的治疗作用

目的研究清肝降浊颗粒对酒精与高脂饲料联合诱导的大鼠脂肪肝是否具有治疗作用。方法采用灌服56%乙醇同时饲喂高脂饲料的方法,诱导建立复合因素导致的脂肪肝大鼠模型。给药4 w后,检测与酒精性脂肪肝密切相关的各项指标。血液生化学指标检测:天冬氨酸氨基转移酶(AST)活性,丙氨酸氨基转移酶(ALT)活性;血清及肝组织中总胆固醇(TC)含量,甘油三酯(TG)含量;肝脏组织中超氧化物歧化酶(SOD)活性,丙二醛(MDA)含量;肝脏、脾脏、胸腺及肾上腺脏器系数。结果清肝降浊颗粒对脂肪肝动物血清AST、ALT、TC和TG水平的异常升高均具有明显的降低作用(P0.01或P0.05);可以升高脂肪肝动物肝组织中SOD活性,降低TC、TG和MDA含量及肝脏系数(P0.01或P0.05)。结论清肝降浊颗粒具有保肝降酶、抑制脂质过氧化反应、降低血脂肝脂含量,从而达到治疗复合因素所致脂肪肝的作用。     

胆宁片对高脂饮食大鼠非酒精性脂肪性肝炎模型形成的影响

目的　高脂饮食建立大鼠非酒精性脂肪性肝炎模型 ,观察中药胆宁片对造模形成的影响。方法　以连续16周的高脂饮食建立大鼠脂肪性肝炎模型 ,治疗组大鼠从高脂饮食 8周起加用胆宁片治疗。测定血脂和血清转氨酶 ,苏木精 伊红染色观察肝脏病理改变 ,并以正常饮食大鼠作为对照。结果　与正常组 (n =6)相比 ,模型组大鼠 (n =12 )血清TC、LDL C、ALT、AST水平显著升高 ,所有造模肝组织均呈现脂肪性肝炎改变 ,模型复制率为 10 0 %。与模型组相比 ,治疗组大鼠 (n =12 )血清TC、LDL C以及肝指数 ( 3 .91± 0 .5 3对 3 .48± 0 .2 9,P <0 .0 5 )显著下降 ,肝组织炎症活动计数显著降低 ( 5 .83± 2 .0 2对 4.2 3± 0 .64 ,P <0 .0 5 ) ,但仍显著高于正常对照组 ,并且血清转氨酶和肝脂肪变性程度在模型组和治疗组之间差异无显著性。结论　持续 16周的高脂饮食可成功复制大鼠非酒精性脂肪性肝炎模型 ,胆宁片对模型大鼠血脂紊乱和肝组织炎症改变有一定改善作用。     

香蕉皮多酚与辛伐他汀对高脂血症大鼠血脂水平的影响

目的以高脂血症大鼠为模型比较香蕉皮多酚、辛伐他汀降血脂及抗氧化作用。方法雄性SD大鼠灌胃给予高脂饲料制备高脂血症大鼠模型。造模的同时,给予香蕉皮多酚、辛伐他汀,连续给药40 d后测定总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙二醛(MDA)的含量,超氧化物歧化酶(SOD)的活性。结果当香蕉皮多酚浓度低于60 mg/kg,辛伐他汀降低血清中的TC、TG的能力、抗氧化能力显著优于香蕉皮多酚组(P0.05),当香蕉皮多酚浓度达到120 mg/kg,香蕉皮多酚降低血清中的TC的能力显著优于辛伐他汀组,抗氧化能力显著优于辛伐他汀(P0.05)。结论香蕉皮多酚对高脂血症模型大鼠具有降低血脂及抗氧化的双重作用。     

Effect of insulin-sensitizing agents in combination with ezetimibe, and valsartan in rats with non-alcoholic fatty liver disease

AIM: To assess whether treatment with insulin-sensitizing agents (ISAs) in combination with ezetimibe and valsartan have greater effect on hepatic fat content and lipid peroxidation compared to monotherapy in the methionine choline-deficient diet (MCDD) rat model of non-alcoholic fatty liver disease (NAFLD). METHODS: Rats (n = 6 per group) were treated with different drugs, including MCDD only, MCDD diet with either metformin (200 mg/kg), rosiglitazone (3 mg/kg), metformin plus rosiglitazone (M R), ezetimibe (2 mg/ kg), valsartan (2 mg/kg), or combination of all drugs for a total of 15 wk. Liver histology, lipids, parameters of oxidative stress and TNF-alpha were measured. RESULTS: Fatty liver (FL) rats demonstrated severe hepatic fatty infiltration (> 91% fat), with an increase in hepatic TG ( 1263%, P < 0.001), hepatic cholesterol ( 245%, P < 0.03), hepatic MDA levels ( 225%, P < 0.001), serum TNF-alpha (17.8±10 vs 7.8±0.0, P < 0.001), but a decrease in hepatic alpha tocopherol (-74%, P < 0.001) as compared to the control rats. Combination therapy with all drugs produced a significant decrease in liver steatosis (-54%), hepatic TG (-64%), hepatic cholesterol (-31%) and hepatic MDA (-70%), but increased hepatic alpha tocopherol ( 443%) as compared to FL rats. Combination therapy with ISA alone produced a smaller decrease in liver steatosis (-32% vs -54%, P < 0.001) and in hepatic MDA levels (-55% vs -70%, P < 0.01), but a similar decrease in hepatic lipids when compared with the all drugs combination. TNF-alpha levels decreased significantly in all treatment groups except in ISA group. CONCLUSION: Combination therapies have a greater effect on liver fat content as compared to monotherapy. Rosiglitazone appears to improve hepatic steatosis to a greater extent than metformin.     

Effects of emodin on treating murine nonalcoholic fatty liver induced by high caloric laboratory chaw

AIM: To investigate the effects of emodin on the treatment of non-alcoholic fatty liver in rats induced by high caloric laboratory chaw. METHODS: Non-alcoholic fatty liver model was successfully established by feeding with high caloric laboratory chaw for 12 wk. Then the model rats were randomly divided into 3 groups, namely model control group, emodin group and dietary treatment group. The rats in emodin group were given emodin at dose of 40 mg/(kg·d) while animals in other groups were given distilled water of the same volume. The rats in model control group were fed with high caloric laboratory chaw while animals in other groups were fed with normal diet. Four weeks later, liver index (liver/body weight ratio), serum activities of liver-associated enzymes, blood lipid, fasting blood glucose, fasting plasma insulin, HOMA insulin resistance index (HOMA-IR), hepatic triglyceride content and histology features of all groups were assayed. The expression of hepatic peroxisomal proliferator activated receptor (PPAR) gamma was determined by RT-PCR. RESULTS: The body weight, liver index, serum activities of alanine aminotransferase (ALT), blood lipid, hepatic triglyceride content of model control group were significantly elevated, with moderate to severe hepatocyte steatosis. The expression of hepatic PPAR gamma mRNA was obviously reduced in model control group. Compared with model control group, the body weight, liver index, serum activities of ALT, blood lipids and hepatic triglyceride of emodin group significantly decreased and hepatic histology display was also greatly improved. Meanwhile, the expression of hepatic PPAR gamma mRNA was elevated. However, high serum activities of ALT and hyperlipidemia were persisted in dietary treatment group although liver index was decreased and liver histology was somewhat improved. CONCLUSION: It is suggested that emodin might be effective in the treatment of non-alcoholic fatty liver in rats. Its therapeutic mechanism could be associated with increasing the expression of hepatic PPAR gamma mRNA.     

甘氨酸对高脂饮食诱导小鼠高脂血症的保护作用

目的研究甘氨酸(Gly)降低高脂血症小鼠血脂的作用。方法将40只小鼠随机分为对照组、高脂组、小剂量和大剂量甘氨酸处理组,在不同处理2周后,取血测定小鼠血酯水平、肝组织丙二醛(MDA)和超氧化物歧化酶(SOD)活性,及观察肝组织病理形态学表现。结果与对照组比,高脂饮食小鼠TC、LDL、HDL-C、MDA含量明显增高(P0.05),SOD活性下降(P0.05);与高脂血症动物比,甘氨酸处理小鼠血TC、LDL明显降低(P0.01),MDA含量下降(P0.05),SOD活性升高(P0.05);高脂血症小鼠肝组织可见弥漫性脂肪变性,而甘氨酸处理动物肝细胞内脂滴小且少。结论甘氨酸可通过调节血脂代谢增强抗氧化能力,从而能防治高脂血症所致的肝脂肪变性。     

抗脂肪肝中剂对大鼠高脂血症防治的实验研究

目的：探讨抗脂肪肝冲剂对高脂血症大鼠脂质代谢的影响,寻求防治高脂血症的有效药物。方法：采用高脂饮食喂养大鼠,形成高脂血症模型,饲以抗脂肪肝冲剂,观察大鼠血清总胆固醇（TC）及甘油三酯（TG）的含量,结果：抗脂肪肝冲剂能显著降低高脂血症大鼠血清中TC含量（与模型对照组比较P＜0．01）及TG含量（大、中、小剂量组与模型对照组比较P＜0．01,P＜0．05,P＜0．05）。结论：抗脂肪肝冲剂能够降低高脂血症大鼠TC、TG的含量,具有防治高脂血症的作用。     

联合应用丹酚酸和氨氯地平对高血压合并高脂血症大鼠的治疗作用

目的：观察丹酚酸联合氨氯地平对高血压合并高脂血症大鼠的治疗作用。方法24只自发性高血压大鼠,高脂饲喂2周后,随机分成氨氯地平组、多达一（苯磺酸氨氯地平阿托伐他汀钙片）组、联合用药组和对照组4组,每组6只。连续给药4周,并继续饲喂高脂,测定大鼠给药前后的血压、血脂,血浆、肝和心肌组织中超氧化物歧化酶（SOD）和丙二醛（MDA）含量。结果治疗4周后,对照组血压升高,HDL- C降低（P＜0.05和0.01）;联合用药组血压、血TG、LDL- C、LDL- C /HDL- C、肝组织TC和TG水平,血浆和心肌组织MDA降低,SOD活性和SOD /MDA比值升高,与对照组比较差异有统计学意义（P＜0.05或0.01）;氨氯地平组和多达一组血压、LDL- C、LDL- C /HDL- C、肝组织TC水平、心肌组织MDA含量降低,心肌组织SOD/MDA比值升高,与对照组比较差异有统计学意义（P＜0.05或0.01）,多达一组肝组织TG低于对照组,差异有统计学意义（P＜0.05）。结论丹酚酸联合氨氯地平能协同增强高血压合并高脂血症大鼠的降压和降脂作用,其作用与抑制脂质过氧化、保护血管内皮功能有关。     

Protective role of supplement with foreign Bifidobacterium and Lactobacillus in experimental hepatic ischemia-reperfusion injury

BACKGROUND AND AIM: Intestinal microflora play a crucial role in some severe liver diseases. The purpose of this study was to evaluate the effects of a Lactobacillus strain and a Bifidobacterium strain on ischemia-reperfusion (I/R) liver injury. METHODS: Rats were divided into six groups. Each group received either Bifidobacterium Catenulatum ZYB0401; Lactobacillus Fermentum ZYL0401; a mixture of these two bacterial strains; gentamicin; or saline by daily gavage for 7 days. On the sixth day, all rats, except those in the control group, were subjected to 20 min of liver ischemia. After 22 h of hepatic reperfusion, liver enzymes and histology, malondialdehyde (MDA), superoxide dismutase (SOD), endotoxemia, serum tumor necrosis factor-alpha (TNF-alpha), intestinal bacteria, intestinal mucosal ultrastructure, and bacterial translocation were studied. RESULTS: All administered bacteria increased intestinal Bifidobacterium and Lactobacillus, decreased endotoxemia (P < 0.01), alanine aminotransferase (ALT) (P < 0.01), and markedly ameliorated liver histology and intestinal mucosal ultrastructure. Only rats treated with Bifidobacterium Catenulatum ZYB0401 and Lactobacillus Fermentum ZYL0401 showed reduced incidence of bacterial translocation to the kidney (P < 0.05), associated with decreased serum TNF-alpha and liver MDA (P < 0.05) and increased liver SOD (P < 0.05) compared to the I/R group. Gentamicin decreased almost all kinds of intestinal bacteria (P < 0.01) and decreased ALT (P < 0.01) and serum TNF-alpha, but failed to reduce both endotoxemia and the incidence of bacterial translocation and had no effects on liver MDA and SOD. CONCLUSION: Bifidobacterium Catenulatum ZYB0401 in combination with Lactobacillus Fermentum ZYL0401 could be useful in restoring intestinal microflora and in preventing liver injury in hepatic I/R of rats.     

辛伐他汀对高脂血症患者内皮功能障碍的干预作用及其与碱性成纤维细胞生长因子的关系

目的 研究辛伐他汀对高脂血症患者血管内皮功能障碍的干预作用及其与血清碱性成纤维细胞生长因子的关系.方法 将54例高脂血症患者按血脂水平随机分为辛伐他汀组(28例,辛伐他汀20 mg/d,8周)和高.脂对照组(26例),另设正常对照组(29例,正常健康受试者).应用彩色多谱勒超声诊断仪测量受试者肱动脉血流介导的舒张功能,评价血管内皮功能的变化.应用酶联免疫吸附双抗体夹心法和硝酸酶还原法检测受试者血清碱性成纤维细胞生长因子和一氧化氮的含量,评价一氧化氮及碱性成纤维细胞生长因子与血管内皮功能障碍的关系.常规检测血清总胆固醇、甘油三酯、低密度脂蛋白及高密度脂蛋白的浓度.结果 8周后,辛伐他汀组与高脂对照组相比肱动脉血流介导的舒张功能明显改善(P<0.05),血清一氧化氮和血清碱性成纤维细胞生长因子含量升高(P<0.05),血清总胆固醇、甘油三酯和低密度脂蛋白浓度明显下降(P<0.01),而高密度脂蛋白浓度明显升高(P<0.01).结论 辛伐他汀可增加血清碱性成纤维细胞生长因子含量,提高一氧化氮含量,改善高脂血症患者血管内皮功能障碍,其作用机制与降低血清总胆固醇、甘油三酯和低密度脂蛋白的浓度有一定关系.