肝脂溶颗粒对非酒精性脂肪肝大鼠脂质代谢及胰岛素抵抗的影响
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:通过高脂饮食诱导非酒精性脂肪肝大鼠模型,观察中药肝脂溶颗粒对实验性大鼠血清HOMA-IR、Leptin及肝脏组织TNF-α、PPARα表达的影响,探讨肝脂溶颗粒对非酒精性脂肪肝干预的作用机制。
     方法:将清洁级Wistar大鼠60只,适应环境7天后随机分为2组,正常组9只,高脂组51只。正常组给予普通饲料喂养,高脂组给予高脂饲料喂养。12周后,在正常组中随机选出1只大鼠,在高脂组中随机选出6只大鼠,处死后取肝脏组织进行HE染色。正常组剩余大鼠继续给予普通饲料喂养。高脂组剩余大鼠随机分为5组:模型组、对照组、肝脂溶颗粒高、中、低剂量组,每组9只大鼠。继续高脂饲料喂养同时每日给予不同药物进行灌胃,正常组和模型组给予生理盐水灌胃(lml/100g);对照组给予多烯磷脂酰胆碱胶囊水溶液灌胃(0.14g/kg);中药组分别给予不同剂量肝脂溶颗粒水溶液灌胃(3g/kg、2.1g/kg、0.9g/kg)。连续灌胃4周后取材,取肝脏组织行HE染色,观察肝脏病理形态学改变;运用放射免疫分析法检测血清HOMA-IR、酶联免疫吸附测定血清Leptin表达、免疫组织化学染色检测肝脏组织TNF-α表达及PCR技术检测肝脏组织PPARα表达。
     结果:
     1肝脂溶颗粒对NAFLD大鼠肝指数的影响
     高剂量组肝指数显著低于对照组,有显著统计学意义(P<0.05);中剂量组肝指数与对照组相比,无统计学意义(P>0.05);低剂量组肝指数高于高、中剂量及对照组,有显著的统计学意义(P<0.05)。
     2肝脂溶颗粒对NAFLD大鼠肝脏病理形态学的影响
     模型组大鼠肝脏组织脂肪变程度最高,与正常组相比有显著性差异(p<0.01);高、中、低剂量组及对照组大鼠肝脏组织的病理改变均有不同程度的改善,肝细胞脂肪变数目和胞浆内脂滴均有不同程度的减少,与模型组相比,差异具有统计学意义(p<0.05);高剂量组大鼠肝脏组织病理学改善明显优于对照组(p<0.05);中剂量组大鼠肝脏组织脂肪变性程度与对照组相比,无明显统计学意义(p>0.05);低剂量组与高、中剂量组及对照组相比,有统计学意义(p<0.05)。
     3肝脂溶颗粒对NAFLD大鼠血清生化指标及HOMA-IR表达影响的研究
     3.1血清生化指标
     模型组和药物干预各组大鼠血清TG、CHOL均高于正常组(P<0.01);高、中、低剂量组和对照组均低于模型组(P<0.01),有显著性统计学意义;高剂量组明显低于对照组(P<0.05),有显著性统计学意义;中剂量组与对照组相比(P>0.05),无显著统计学意义;低剂量组高于高、中剂量组及对照组(P<0.05),有统计学意义。各组NAFLD大鼠血清ALT、AST较正常组均有显著的升高(P<0.01);模型组大鼠血清ALT、AST水平最高,与其它药物干预组相比(P<0.01),有显著统计学意义;高剂量组大鼠血清ALT、AST水平低于对照组(P<0.05),有显著统计学意义;中剂量组大鼠血清ALT、AST水平与对照组相比(P>0.05),无统计学意义;低剂量组大鼠血清ALT、AST水平明显高于高、中剂量组及对照组(P<0.01),有统计学意义。说明在改善NAFLD大鼠肝功能(ALT、AST)方面,肝脂溶颗粒效果优于多烯磷脂酰胆碱胶囊。血清游离脂肪酸FFA以正常组最低,与其它各组相比(P<0.01),有显著统计学意义;以模型组最高,与其它药物干预各组相比(P<0.01),有显著统计学意义;高剂量组血清FFA含量明显低于对照组(P<0.05),有显著统计学意义;中剂量组血清FFA含量与对照组相比(P>0.05),无显著统计学意义;低剂量组血清FFA含量均高于高、中剂量组及对照(P<0.01),有统计学意义。
     3.2血清HOMA-IR表达
     各组NAFLD大鼠空腹血糖、胰岛素和IR均明显高于正常组(P<0.01),有显著统计学意义;而模型组大鼠空腹血糖、胰岛素和IR最高,明显高于各药物干预组(P<0.01),有显著统计学意义;高剂量大鼠空腹血糖、胰岛素和IR明显低于对照组(P<0.01),有显著统计学意义;中剂量组大鼠空腹血糖、胰岛素和IR低于对照组(P<0.05),有统计学意义;低剂量组大鼠空腹血糖、胰岛素和IR与对照相比较(P>0.05),无统计学意义。
     4肝脂溶颗粒对NAFLD大鼠血清Leptin表达影响的研究
     各组NAFLD大鼠血清Leptin的含量均明显高于正常组(P<0.01),有显著统计学意义;模型组大鼠血清Leptin的含量最高,与其它药物干预组相比有显著差异(P<0.01),有统计学意义;高剂量组大鼠血清Leptin的含量明显低于对照组(P<0.05),有统计学意义;中剂量组大鼠血清Leptin的含量与对照组相比较(P>0.05),无显著统计学意义;低剂量组大鼠血清Leptin的含量与高、中剂量组及对照组相比(P<0.05),有统计学意义。
     5肝脂溶颗粒对NAFLD大鼠肝脏组织TNF-α表达影响的研究
     各NAFLD模型组大鼠肝脏组织内TNF-α的表达明显高于正常组(P<0.01),具有显著性统计学意义;模型组大鼠肝脏组织内TNF-α的表达明显高于各药物干预组(P<0.01),具有显著性统计学意义;高剂量组大鼠肝脏组织内TNF-α的表达低于对照组(P<0.05),具有显著性统计学意义;中剂量组大鼠肝脏组织内TNF-α的表达与对照组相比较(P>0.05),无显著性统计学意义;低剂量组大鼠肝脏组织内TNF-α的表达与高、中剂量组及对照组相比较(P<0.05),有统计学意义。
     6肝脂溶颗粒对NAFLD大鼠肝脏组织PPARα表达影响的研究
     正常组明显高于其它各组(P<0.01),有显著统计学意义;模型组明显低于其它各组(P<0.01),有显著统计学意义;高剂量组最接近正常组,显著高于其它药物干预组(P<0.05),有显著统计学意义;中剂量组与对照组相比(P>0.05),无显著统计学意义;低剂量组低于高、中剂量组及对照组(P<0.05),有显著统计学意义。
     结论:
     1肝脂溶颗粒能改善实验性NAFLD大鼠的一般状态,减轻肝内脂质沉积,改善肝脂肪变性程度。
     2肝脂溶颗粒有一定保护肝功能、降低转氨酶、调节血脂异常、改善胰岛素抵抗,恢复正常糖脂代谢的作用。
     3肝脂溶颗粒明显降低血清Leptin表达、降低肝脏组织TNF-α表达、增强肝脏组织PPARαmRNA表达。
     4肝脂溶颗粒通过减轻肝内脂质沉积,改善肝脂肪变性程度;保肝、降酶、降脂,而体现对非酒精性脂肪肝有良好的防治作用。
     5肝脂溶颗粒通过改善IR、抑制血清Leptin表达、抑制肝脏组织TNF-α表达、增强肝脏组织PPARαmRNA表达,增加胰岛素敏感性,调节脂质代谢,促进脂肪酸氧化分解,减轻肝脏脂肪变性,从而发挥对非酒精性脂肪肝的治疗作用,这可能是肝脂溶颗粒防治非酒精性脂肪肝的机制之一。
Purposes:Through the high fat diet-induced non-alcoholic fatty liver rat model,observation on liver lipid soluble granule on experimental rat serum HOMA-IR, Leptin andliver tissue TNF-α, PPAR α expression effects on hepatic lipid soluble, particles ofnon-alcoholic fatty liver intervention mechanism.
     Methods: Will clean in60Wistar rats, to adapt to the environment after7days wererandomly divided into2groups, the normal group9, high fat group51.Normal group weregiven general feeding, high lipid group were fed high fat diet.12weeks later, in the normalgroup selected randomly from1rats, in hyperlipidemia group selected randomly from6rats,were killed after liver tissues were stained with HE.The normal group the remaining ratscontinued to give ordinary feed.High lipid group remaining rats were randomly divided into5groups: control group, model group, hepatic lipid soluble granule high, low dose group,9ratsin each group.Continue the feeding high-fat diet and daily administration of different drugs togastric lavage, normal group and model group were given saline (lml/100g); the control groupwas given the polyene phosphatidylcholine capsule solution intragastrically (0.14g/kg);traditional Chinese medicine group were treated with different doses of liver fat solubleparticles in aqueous solution (3g/kg,2.1g/kg, gastric perfusion0.9g/kg).Consecutive gavagefor4weeks after operation, the liver tissue stained with HE, were observed in the liverpathological change; by radioimmunoassay in detection of serum HOMA-IR, enzyme linkedimmunosorbent assay of Leptin expression, immunohistochemical staining for detection ofliver tissue TNF-α expression and PCR technique for the detection of liver tissue PPAR αexpression.
     Result:
     1Liver lipid soluble particle effects on NAFLD rats liver index
     The high dose group of liver index was significantly lower than the control group, therewas significant(P<0.05); the middle dose group of liver index compared with the controlgroup, no statistical significance(P>0.05); low dose group of liver index higher than high,middle dose and control group, there was a statistically significant difference(P<0.05).
     2Liver fat soluble granule on NAFLD rat liver pathological and morphological effects
     The model of liver tissue steatosis degree is the highest in rats of group, there wassignificant difference compared with the normal group (p<0.01); high, medium, low dosegroup and the control group of rats liver tissue pathological changes were improved, liversteatosis and reduce the number of cytoplasmic lipid droplets in varying degrees, comparedwith with the model group, the difference was statistically significant (p<0.05); high dosegroup rats liver tissue were significantly better than the control group (p<0.05); the middledose group rats liver tissue steatosis compared with the control group, no statisticalsignificance (p>0.05); low dose group, middle dose group compared with control group, therewas statistical significance (p<0.05).
     3Liver fat soluble granule on NAFLD rat serum biochemical index and HOMA-IRexpression of
     3.1Serum biochemical indexes
     The model group and drug intervention group rats serum TG, CHOL, FFA were higherthan those in the normal group (P<0.01); high, low dose group and control group were lowerthan those in the model group (P<0.01), there is statistical significance; the high dose groupwas significantly lower than that of the control group (P<0.05), a significant; compared withmiddle dose group and the control group (P>0.05), no significant difference; low dose groupwas higher than that of high, middle dose group and the control group (P<0.05), there wasstatistical significance.
     Detection results show that the groups of NAFLD rats serum ALT and AST weresignificantly increased in the normal group (P<0.01); Model group rats serum ALT, AST levelthe highest, compared with other drug intervention group (P<0.01), there is significantstatistical significance; High dose group of rats serum ALT, AST level is lower than thecontrol group (P<0.05), there is significant statistical significance; Dose group of rats serumALT, AST level compared with the control group (P>0.05), no statistical significance; Lowdose group of rats serum ALT, AST level significantly higher than the high, middle dosegroup and control group (P<0.01), with statistical significance. Instructions to improveNAFLD rats liver function (ALT, AST), liver lipid soluble particle effect is better than that ofpolyene phosphatidylcholine capsules.
     Serum free fatty acid FFA in normal group were the lowest, compared with the othergroups (P<0.01), there was significant; the model group was the highest, compared with otherdrug intervention group (P<0.01), there was significant; high dose group, serum FFA wassignificantly lower than that of the control group (P<0.05), there was significant statisticalsignificance the serum content of FFA; the middle dose group compared with the controlgroup (P>0.05), no significant difference of serum FFA content; low dose group were higherthan those of high, middle dose group and control (P<0.01), there was statistical significance.
     3.2Expression of serum HOMA-IR
     Groups of NAFLD rats fasting blood glucose, insulin and IR were significantly higherthan that in normal group (P<0.01), there was significant; while the fasting blood glucose,insulin and IR in the rats of model group was significantly higher than that of the highest,drug intervention group (P<0.01), there was significant; high dose rats fasting blood glucose,insulin and IR significantly lower than the control group (P<0.01), there was significant; themiddle dose group rats, fasting blood glucose, insulin and IR lower than that of the controlgroup (P<0.05), there was significant; low dose group rats, fasting blood glucose, insulin andIR compared with the control (P>0.05), no statistical significance.
     4Liver fat soluble granules on NAFLD rat serum Leptin express impact studies
     The Leptin content in serum of rats in each group of NAFLD were significantly higherthan normal group (P<0.01), there was significant; the serum Leptin in the rats of modelgroup was the highest, compared with other drug intervention group were significantlydifferent (P<0.01), there is statistical significance; the Leptin content in serum of rats in highdose group was lower than that of the control group (P<0.05), there is statistical significance;serum Leptin rats dose content compared with the control group (P>0.05), no statistical significance; the content of serum Leptin in rats of low dose compared with high, middle dosegroup and the control group (P<0.05), there was statistical significance.
     5Liver fat soluble granules on NAFLD rat liver tissue TNF alpha express impactstudies
     The expression of NAFLD in liver tissue of rats in model group of TNF-α was higherthan that in normal group (P<0.01), with significant statistical significance; expression ofliver tissue in rats of model group was significantly higher than that of TNF-α in the drugintervention group (P<0.01), with significant statistical significance; expression in liver tissueof rats in high dose group of TNF-alpha is lower than that of the control group (P<0.05), withsignificant statistical significance; liver tissue dose group rats TNF-expression compared withthe control group (P>0.05), no significant difference; the expression of liver tissue in rats oflow dose group, TNF-α with high, middle dose group and the control group. Comparison(P<0.05), there was statistical significance.
     6liver fat soluble granules on NAFLD rat liver tissue PPAR α express impact studies
     The normal group was significantly higher than that in the other groups (P<0.01), therewas significant; the model group was significantly lower than that of other groups (P<0.01),there was significant; high dose group was the most close to the normal group, theintervention group was significantly higher than that of other drugs (P<0.05), there wassignificant; compared with middle dose group and the control group (P>0.05), no statisticalsignificance; low dose group were lower than those in high, middle dose group and thecontrol group (P<0.05), there was significant.
     Conclusion:
     1. Liver fat soluble granules can improve experimental NAFLD rat general condition,reduce the intrahepatic lipid deposition, improve the degree of hepatic steatosis.
     2Liver fat soluble granules have certain protection liver function, reduce thetransaminase, regulating dyslipidemia, improving insulin resistance, restore normal glucolipidmetabolism role.
     3Liver fat soluble granules obviously decrease serum Leptin expression, reduce the livertissue TNF alpha expression, strengthen liver tissue PPAR α mRNA expression.
     4Liver fat soluble granules through can reduce intrahepatic lipid deposition, improvehepatic steatosis degree; Protect liver, reduce enzyme, fall fat, and reflect on nonalcoholicfatty liver disease have good control effect.
     5Liver fat soluble granules by improving IR, inhibition of serum Leptin expression,inhibiting liver tissue TNF alpha expression, strengthen liver tissue PPAR α mRNAexpression, increase insulin sensitivity, regulate lipid metabolism, promote the fatty acidoxidation decomposition, reduce the liver steatosis, thus play on nonalcoholic fatty liverdisease treatment effect, this may be liver fat soluble particle control nonalcoholic fatty liverdisease is one of the mechanisms.
引文
[1]陈润花.非酒精性脂肪性肝病的中医证候特点研究[M].北京中医药大学硕士学位论文,2008
    [2]朱文峰.国家标准应用:中医内科疾病诊疗常规[M].长沙:湖南科学技术出版社,1999:395-396
    [3]赵秀莉.中医辨治脂肪肝[J].中国社区医师,2003,19(16):13
    [4]刘天虹.健脾益肾祛瘀法治疗脂肪肝34例[J].河北中医,2004,26(11):818
    [5]王中琳.“血浊”病因病机浅谈[J].中国中医药现代远程教育,2009,7(8):81
    [6]杨智海.刘吉善治疗非酒精性脂肪肝的临床经验[J].光明中医,2008,23(12):1915
    [7]于丰彦,周小军,周福生.周福生教授治疗脂肪肝经验介绍[J].陕西中医学院学报,2008,6:19-20
    [8]乔娜丽,杨钦河,纪桂元,等.论肝郁脾虚是脂肪肝的基本发病病机[J].时珍国医国药,2008,19(5):238-239
    [9]曲丽丽,史焱.浅谈从脾论治高脂血症[J].2009,7(3):82
    [10]董志,王述文.试论浊病病机[J].中国中医药现代远程教育,2011,26(3):420
    [11]纪桂元,杨钦河,谢维宁,等.从痰湿探讨胰岛素抵抗致非酒精性脂肪肝的发病机理[J].辽宁中医杂志,2007,34(8):1063
    [12]胡义扬.加强中医药治疗脂肪性肝病的深入研究[J].中国中西医结合杂志,2004,24(1):12
    [13]张大明,杨建宇.高脂血症属“痰”属“脂”之辩[J].中国中医药现代远程教育,2008,6(5):401
    [14]冯志海.痰湿与2型糖尿病高脂血症的关系[J].中国中医药现代远程教育,2008,6(10):1145
    [15]郁相云,钟建华,张旭.泽泻降血脂药理作用及物质基础研究[J].中国中医药现代远程教育,2010,8(11):250
    [16]辛爱洁.中医“痰浊”与高甘油三酯血症相关性探讨[J].光明中医,2010,25,(9):1695
    [17]宰军华,孙利军,李恒.中西医对肥胖人群痰湿体质的认识[J].光明中医,2011,26(4):626
    [18]广州中医药大学《中医内科五脏病学》编委会.中医内科五脏病学[M].广州:广东科技出版社,2001:3
    [19]胡美兰.脂肪肝的中医病因病机探讨[J].中国中医药现代远程教育,2003,1(12):734
    [20]徐列明,胡义扬.脂肪肝的中药治疗.中西医结合学报,2003,1(2):138-141
    [21]吴茂林.脂肪肝中医病机及论治思路浅探[J].河北中医,2007,29(6):515-516
    [22]叶未设.中医对脂肪肝的认识及防治[J].中国热带医学,2004,4(6):1023
    [23]潘丰满,杨钦河,沈英森.脂肪肝中医病因病机特点探讨[J].陕西中医,2004,25(9):823-825
    [24]谭远忠,魏文斌.中西医结合治疗非酒精性脂肪肝的观察[J].湖北中医杂志,2007,29(2):26
    [25]陈超.吴门医派络病理论之病因病机学说在慢性肝病中的应用[J].中国中医药现代远程教育,2010,8(14):3
    [26]汤曙浩.化湿逐瘀法治疗脂肪肝67例[J].江西中医药,2006,37(281):31
    [27]郭子光.现代中医治疗学[M].2版.成都:四川科学技术出版社,2002:203-204
    [28]缪伟峰,金小晶.脂肪肝中医发病机制的探讨[J].江西中医学院学报,2008,5:5-6
    [29]周祺.于志强治疗脂肪肝的经验[J].河北中医,2009,7:965-966
    [30]潘志敏,李玉花.脂肪肝的病机及治疗研析[J].浙江中医杂志,2004,(1):8-9
    [31]周琪,刘鉴.李军教授从痰疲论治脂肪肝临床经验探要[J].实用中医内科杂志,2008,22(l):15-16
    [32]陈润芝,张连枝,崔宁,等.中医辨证施治脂肪肝140例观察[J].泰山医学院学报,2003,19(10):522
    [33]李振爽,陈霞.论毒瘀与代谢综合征[J].光明中医,2010,25(4):565
    [34]宋新安,张兆航,郭大山.试述“浊淫三焦”与代谢综合征[J].光明中医,2011,26(5):878
    [35]马晓燕,吕娇娇,张岩.脂肪肝中医“气虚痰毒”证实验研究[J].辽宁中医杂志,2012,39(20):200
    [36]车慧,刘文科,郭允,等.从“膏浊病”理论谈代谢综合征合并脂肪肝的治疗[J].中医杂志,2012,53(7):560
    [37]刘平.现代中医肝脏病学[M].北京:人民卫生出版社,2002:280-281
    [38]银醇云.辨证治疗脂肪肝58例临床观察[J].湖南中医药导报,2003,9(8):20-21
    [39]刘晓平.脂肪肝中医辨治四法.中西医结合肝病杂志,2005,15(15):306-307
    [40]张卫东.脂肪肝从脾论治三法[J].中医药临床杂志,2006,18(4):359
    [41]刘文全,高红叶,张琴.辨证与辨病结合治疗非酒精性单纯性脂肪肝133例疗效观察[J].新中医,2005,37(9):43
    [42]阎蔚,刘敏.中医辨证分型治疗脂肪肝对患者体重指数、腰臀围比及血糖血脂水平影响的临床研究.新中医,2006,38(6):42-43
    [43]李少东,李红山,冯琴,等.脂肪肝中医证型分类的文献分析.中西医结合肝病杂志,20062006,16(4):255-256
    [44]许剑,涂燕云.辨治脂肪肝经验[J].河南中医,2006,26(11):24-25
    [45]陈姝娴,应爱兰.辨证分型治疗脂肪肝探识[J]实用中医内科杂志,2006,20(4):384
    [46]罗军.脂肪肝的辨证施治[J].陕西中医,2005,26(12):1339
    [47]杨晋原.脂肪肝中医辨治五法.山西中医学院学报,2006,7(1):63-64
    [48]杨钦河,凌家生,平换换,等.非酒精性脂肪肝的中医药防治思路与对策[J].中医杂志,2007,48(8):746
    [49]韩加强,孟庆敏.脂肪肝的辨证论治[J].亚太传统医药,2007,3(2):62
    [50]丁怡敏.中医辨证治疗脂肪肝疗效观察.中国社区医师综合版,2006,6(8):231-233
    [51]赵文霞,段荣章,李建国,等.赤芍防治大鼠非酒精性脂肪肝模型作用机制的实验研究[J].中医研究,2005,18(3):13-16
    [52]江庆澜,李瑜元,潘锦瑶,等.虎杖提取液对非酒精性脂肪肝大鼠肿瘤坏死因子α基因表达的影响[J].中药材,2005,28(10):917-919
    [53]董慧,陆付耳,高志强,等.大黄素治疗高脂饮食诱发的大鼠非酒精性脂肪肝的实验研究[J].中国中西医结合杂志,2006,6(26):64-67
    [54]代东伶,沈薇,管晓琴.虫草菌丝对实验性大鼠非酒精性脂肪肝解偶联蛋白2的影响[J].中华肝脏病杂志,2005,13(6):464-465
    [55]张新星,沈薇,虫草菌丝对非酒精性脂肪肝病大鼠肝细胞凋亡的作用及其相关机制[J].胃肠病学和肝病学杂志,2006,15(5):478-484
    [56]杨朝霞,沈薇,代东伶.虫草菌丝对实验性大鼠非酒精性脂肪肝的疗效观察及其分子机制探讨[J].重庆医药,2006,35(18):1671-1673
    [57]何自立,陈伟平,单巍.蚕蛹油对大鼠非酒精性脂肪肝形成的影响[J].中国微生态杂志,2007,19(6):483-485
    [58]孙丽伟,黄妙珍.丹参对非酒精性脂肪肝大鼠血清MDA、SOD、TNF、Leptin的影响[J].浙江中医药大学学报,2007,31(6):696-698
    [59]郭建利,张睦清,韩雪,等.丹参不同组分防治大鼠非酒精性脂肪肝模型作用机制的研究[J].河北中医药学报,2012,27(1):8-9
    [60]谭德安,府伟灵,周智广,等.姜黄素治疗大鼠非酒精性脂肪肝病的实验研究[J].重庆医学,2007,36(16):1626-1628
    [61]蒋利和,史岩,张玉芳,等.白苏油对非酒精性脂肪肝作用的研究[J].食品科学,2008,29(12):658-662
    [62]郑培永,马赞颂,花永强,等.葛根素对非酒精性脂肪性肝病大鼠肝脏瘦素受体mRNA和磷酸化Janus激酶2/磷酸化信号转导与转录激活因子3的影响[J].中西医结合学报,2008,6(9):921-927
    [63]纳青青,谢华,三七总甙对非酒精性脂肪肝大鼠肝组织细胞色素P4502E1表达的影响[J],实用肝脏病杂志,2008,11(4):33-235
    [64]姜秀娟,王旭辉,丁晓猛,等.木贼对食饵性脂肪肝大鼠肝细胞增殖与凋亡的影响[J].时珍国医国药,2011,22(5):1163-1164
    [65]曹宁,郭文洁,唐佳瑜,等.乌药叶总黄酮对高脂血症脂肪肝小鼠模型的降脂作用[J].中药新药与临床药理,2011,22(2):149-153
    [66]朱炜,俞宏斌,戴闯,等.余甘子对大鼠非酒精性脂肪肝疾病中肝损伤和炎症的抑制作用研究[J].医学研究杂志,2012,41(2):140-143
    [67]陈丽,张绪东,焦杨,等.玉郎伞提取物对食饵性高脂血症大鼠肝脏脂蛋白代谢相关酶活性及脂肪肝的影响[J].中国实验方剂学杂志,2012,18(9):254-258
    [68]刘锐,李劲平,伍娟娟,等.丹苘软胶囊对非酒精性脂肪肝模型大鼠胰岛素抵抗及瘦素抵抗的影响[J].中国实验方剂学杂志,2012,18(1):188-191
    [69]刘锐,李劲平,伍娟娟,等.丹苘软胶囊对非酒精性脂肪肝模型大鼠肝脏SOCS-3mRNA表达的影响[J].中华中医药学刊,2012,30(1):191-193
    [70]闫曙光,周永学,惠毅.通便玉蓉丸治疗非酒精性脂肪肝及高脂血症的实验研究[J].陕西中医.2012,33(1):111-113
    [71]钟成,潘竞锵,吕俊华,等.茵陈蒿汤对代谢综合征-脂肪肝大鼠增强胰岛素敏感性及抗脂肪肝作用[J].临床医学工程,2012,19(4):520-523
    [72]陈玉翠,周岳君,赵国强,等.脂易消对非酒精性脂肪肝CYP2E1基因表达的调控[J].中国医学创新,2012,9(2):136-137
    [73]钟骏慧,江洪.祛脂涤浊汤对非酒精性单纯性脂肪肝患者胰岛素抵抗的影响[J].中国中医急症,2001,21(3):449-450
    [74]刘素英,徐明庚,宋小秋.自拟消脂方治疗非酒精性脂肪肝临床研究[J].中外医疗,2012,6:136
    [75]李文彦,吕云佳,方顺济.自拟脂肪肝合剂治疗非酒精性脂肪肝病的疗效观察[J].上海中医药杂志,2012,46(6):36-38
    [76]王丽华.安络化纤丸治疗非酒精性脂肪肝临床观察[J].中国社区医师,2012,14(303):234
    [77]胡洪涛,蒋开平,李建鸿,等.柴胡温胆汤治疗非酒精性脂肪肝50例临床观察[J].中医临床研究,2012,4(10):3-5
    [78]田凌云.自拟清脂汤治疗非酒精性脂肪肝58例[J].中国民间疗法,2012,20(2):32-33
    [79]路波,杨栓柱.运脾化浊冲剂治疗非酒精性脂肪肝疗效观察[J].陕西中医,2012,33(4):449-451
    [80]应续芹.自拟调脂汤治疗脂肪肝临床分析[J].当代医学,2012,18(3):154-155
    [81]朱熔,王宇静,余泽云.亚虎保肝汤治疗非酒精性脂肪肝80例临床观察[J].中国社区医师,2012,3(14):195-196
    [82]陈刚俊.疏肝活血降脂汤治疗脂肪肝疗效观察[J].实用中医药杂志,2012,28(4):270-271
    [83]张莉,洪哲明.培土运脾法治疗非酒精性脂肪肝43例疗效观察[J].四川中医,2012,30(6):89-90
    [84]崔凯.橘黄降脂汤治疗非酒精性脂肪肝58例[J].河南中医,2012,32(5):580-581
    [85]王小强.健脾升清祛浊汤治疗非酒精性脂肪肝肝功能异常135例[J].山东中医杂志,2012,31(3):161-162
    [86]李刚,李尤玲,谭华炳,等.活血化痰方治疗非酒精性脂肪肝30例总结[J].湖南中医杂志,2012,28(3):41-42
    [87]钱海青.化痰祛瘀汤治疗非酒精性脂肪肝55例[J].浙江中医杂志,2012,47(5):330
    [88]黄梅,张燕,韩平,等.复方沙棘胶囊治疗非酒精性脂肪肝70例疗效观察[J].西部医学,2012,24(2):359-361
    [1] Galdwell SH,hesPenheide EE.Subacute Liver Failure in obese women.AM[J].Gastruenterology,2001,97(8):2058-2062
    [2] Day CP, JamesOF. Steatohepatitis a tale of tw“ohits”[J].Gastro-enterology,1998,114(4):842-845.
    [3]余小虎,朱金水,邱夏地,等.水飞蓟素联合二甲双胍治疗肥胖型非酒精性脂肪肝的临床研究[J].实用肝脏病杂志,2005,8(5):269-271
    [4]于雷,牛俊奇.非酒精性脂肪肝研究新进展[J].中国老年学杂,2007,11(27):2148-2151
    [5]阮希成,蔡奕琪,肖建宏等.罗格列酮治疗非酒精性脂肪肝的初步研究[J].中国实用医药,2009,4(28):123-124.
    [6]向阳,叶家润,李新萍.吡格列酮对非酒精性脂肪肝的疗效观察[J].临床肝胆病杂志,2007,23(6):434-435.
    [7] Marchesini G,Brizi M,Bianchi G,et al.Metformin in non-alcoholic steatohep-atitis.TheLancet,2001,358:893-894.
    [8]倪利英.二甲双胍治疗非酒精性脂肪肝的疗效观察.中国现代医[J].2012,50(2):50-51
    [9] Mazza A,Fruci B, Garinis GA, et al. The role of metformin in the Managemen toFNAFLD[J].Exp Diabetes Res,2012,2012:716404
    [10] Idilm an R,M izrak D,C orapcioglu D,et al.Clinical trial:Insulin-sensitizing agentsmayreduce consequences of insulin resistance in individuals with nonal coholicsteatohepatitis[J].A lim entPharm acol Ther,2008,28:200-208
    [11] Loom ba R,Lutchm an G,Kleiner DE,et al. Clinical trial:pilot study of metform in forthe treatm entofnon-alcoholic steatohepatitis[J]. Alim entPharm acolTher,2009,29:172-182
    [12]谭丽,管小琴,王倩.维生素E、亚硒酸钠对非酒精性脂肪肝作用的实验研究[J].重庆医科大学学报,2007,32(6):606-609
    [13]杨慧莹,林克荣.水飞蓟素治疗脂肪肝的作用机制[J].中华现代内科学杂志,2006,3(8):876-878.
    [14] Salamone F,Galvano F,Cappello F,et al.Silibinin modulates lipid ho-meostasis andinhibits nuclear factor kappa B activation in experimental nonalcoholic steatohepatitis[J].Transl Res,2012,12(15):197-199
    [15]张宝华.水飞蓟素治疗脂肪肝的临床研究[J].中国医药指南,2011,13(9):132-133
    [16]李英姿,边城,张玉臣.α-硫辛酸防治非酒精性脂肪肝大鼠的作用机制[J].泰山医学院学报,2007,8(10):787-789
    [17]季莉莉,周虹,李贤标,等.大豆异黄酮对动脉硬化大鼠的抗氧化作用研究[J].中国预防医学杂志,2006,7(1):1-4
    [18] Yalniz M,Bahcecioglu IH,Kuzu N,et al.Preventive role of genistein in an experimentalnon-alcoholic steatohepatitis model[J].Journal of Gastroenterology and Hepatology,2007,22(11):2009-2014
    [19]崔春吉,金元哲,金东洙,等.大豆异黄酮对非酒精性脂肪肝病大鼠的作用[J].解剖科学进展,2009,15(4):380-382
    [20]林宗梅,蔡妙国,何泽宝.熊去氧胆酸治疗非酒精性脂肪肝疗效观察[J].海峡药学,2009,21(10):147-148.
    [21] Arisawa S,Ishida K, Kameyama N, et al.Ursodeoxycholic acid induces glutathionesynthesis through activation of PI3K/Akt pathway in HepG2cells[J].Biochempharmacol,2009,77(5):858-866
    [22]郭开生.熊去氧胆酸治疗脂肪肝的疗效[J].临床荟萃,2002,17(9):526-527
    [23]杨文义,韩大正,闫春晓.熊去氧胆酸治疗脂肪肝的临床研究[J].中国医药指南,2012,10(12):133-134
    [24]高晶,刘蓉昕.非酒精性脂肪性肝病的治疗进展.国外医学,消化系统疾病分册,2003,23(6):332-336.
    [25]曹亮,张炜.辛伐他汀治疗非酒精性脂肪肝临床观察[J].中国实用医药,2009,4(2):144-145.
    [26]刘梅,陆伦根,曾民德.弹性蛋白酶在脂肪性肝病和肝纤维化治疗中的应用进展[J].国际消化病杂志,2006,26(3):1522154
    [27]杨彦平.弹性酶治疗高脂血症伴非酒精性脂肪肝的临床观察[J].中国现代药物应用,2009,3(3):77-78
    [28]徐丽妹,张瑛华.己酮可可碱对非酒精性脂肪肝大鼠能量储备的影响[J].实用医学杂志,2009,25(9):1380-1382.
    [29] Adama LA, Zrin CO, Angulo P, et al.A pilotrial of PentoXifylline in nonaleoholicsteatohePatitis[J].Am J Gastroenterol,2004,99:2365-2368.
    [30]田培营,王炳芳.非酒精性脂肪肝研究进展[J].同济大学学报(医学版),2006,27(增刊):46.
    [31] Tokita H,Murai S,KamitsukasaH,et al. Influence of TTvirus on the histopathologicalfeatures of nonalcoholic fattyliver disease[J].Hepatol Res,2001,19(3):197.
    [32]金怒云,余小虎.还原型谷胱甘肽治疗非酒精性脂肪肝40例[J].临床药学杂志,2005,14(12):79.
    [33]陈岳祥,刘苏.牛磺酸治疗非酒精性脂肪肝19例临床观察.中国实用内科杂志,2005,25(3):249-250
    [34]高丽.甘乐治疗慢性乙型肝炎并脂肪肝(67例)[J].中国冶金工业医学杂志,2004,21:261.
    [35]杨海发.二氯醋酸二异丙胺治疗非酒精性脂肪肝42例临床分析.中国民康医学[J],2012,24(3):322-323
    [36]程勇,于锋.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.中国临床药理学与治疗学[J],2012,17(1):15-19
    [37]初晓霞,王莉,王慧.还原型谷胱甘肽的临床应用[J].现代医药生,2008,24(21):3244-3245
    [38]杨朝霞,代东伶,沈薇.还原型谷胱甘肽对实验性大鼠非酒精性脂肪肝的疗效观察及其分子机制探讨[J].重庆医科大学学报,2005,30(6):803-807
    [39]王瑞荣.多烯磷醋酞胆碱治疗非酒精性脂肪肝临床观察[J].中国误诊学杂志,2009,9(3):578-579.
    [40]黄德周.多烯磷脂酰胆碱治疗非酒精性脂肪肝80例.中国药业[J],2012,21(7):49-50
    [41]张琦,杨小平,张晓龙,等.凯西莱治疗非酒精性脂肪肝146例疗效观察[J].实用肝脏病杂志,2004,7:42.
    [42]李振军,曲鹏,刘明刚,等.硫普罗宁治疗非酒精性脂肪肝病的疗效观察[J].中国伤残医学,2012,10(2):55-56
    [43]李洁.非酒精性脂肪肝疾病的研究进展[J].东南国防医药,2008,10(4):280-282
    [1]钟岚,范建高,王国良,等.肥胖、高脂血症性脂肪性肝炎模型的建立[J].实验动物科学与管理,2000,17(2):16-20
    [2]范建高,曾民德,李继强,等.Bezafibratedul对大鼠高脂血症和脂肪肝形成的影响.胃肠病和肝脏病学杂志,1999,2(6):100
    [3]华天爵,符丽,赵云静,等.中药降脂合剂对饮食诱导肥胖大鼠的血脂代谢及脂质过氧化水平干预作用的研究[J].广西医科大学学报,2004,21(4):520-521
    [4]李文岗,张学文,何尔斯泰,等.大鼠脂肪肝模型的建立[J].吉林大学学报(医学版),2004,30(2):233-235
    [5] Teramoto K, John L, Bower S, et al. A rat fatty liver transplant model [J]. ransplantation,1993,55:737-741
    [6] Charles S Lieber,Maria A Leo,KiM Mak, et a.l Model of nonalco-holic steatohepatitis[J].American Journal of Clinical Nutrition,2004,79(3):502-9.
    [7]祁培宏,余莉芳.消脂保肝饮抗大鼠脂肪肝的作用[J].中西医结合肝病杂志,2000,10(5):33-35
    [8] Zou Y, Li J, Lu C, et al Highfat emulsion induced rat model of non-alcoholicsteatohepatitis [J].Life Sci,2006,79(11):1100-1107
    [9] Zheng JF, Wang HD, Liang LJ. Protective effects of nitricoxide on hepatic steatosisinduced by total parenteral nutrition in rats [J].Acta Pharmacol Sin,2002,23,(9):824-828
    [10]孙创斌.去脂软肝丸对四环素致小鼠脂肪肝模型肝脂的影响[J].云南中医学院学报,2002,325(1)1-4
    [11]范建高,曾民德.脂肪性肝病[M].北京:人民卫生出版社,2005;170
    [12]孙蓉.脂肝清颗粒对脂肪肝模型大鼠的影响[J].中药新药与临床药理,2003,14(5):313-316
    [13] Chung H, Hong DP, Kim HJ, et al. Differential geneexpression profiles in thesteatosis/fibrosis model of rat liver by chronic administration of carbon tetrachloride[J].Toxicol Appl Pharmacol,2005,208(3):242-254
    [14]顾恪波,张卓,李道本,等.小剂量CCl4皮下注射结合高脂饮食制造大鼠非酒精性脂肪肝模型的研究[J].中西医结合肝病杂志,2004,14(5):284-286
    [15]刘英宏.脂肝消胶囊治疗脂肪肝的实验研究[J].中国中医药科技,2000,7(4):269
    [16]李文彪.清源调脂胶囊治疗高脂血症性脂肪肝实验研究[J].中西医结合肝病杂志,2001,11(3):159-161
    [17]秦红波,曹浩强,华志元,等.高脂饮食致大鼠非酒精性脂肪肝模型的建立[J].南京医科大学学报(自然科学版),2008,28(8):973-976
    [18]王倩,管小琴.大鼠非酒精性脂肪肝造模方法的改进[J].世界华人消化杂志,2007,15(1):1219-1224
    [19]胡克章,杨坤,黄正明.高糖高脂肪饲料诱导大鼠非酒精性脂肪肝的实验研究[J].解放军药学学报,2009,25(2):136-1388
    [20]张瑜,李琳琳,张嫣之,等.非酒精性脂肪肝大鼠模型的建立[J].新疆中医,2007,25(2):7-9
    [21]薛长勇.下丘脑腹内侧核损伤大鼠脂肪肝形成机制探讨[J].营养学报,2002,24(1):58-61
    [22] Jones M E,Thorburn A W,Britt K L,et al.Aromatase-deficient (ArKO) mice accumulateexcess adipose tissue [J].J Steroid Biochem Mol Biol,2001,79(1-5):3-9
    [23] Lin HZ,Yang SQ,Chuckaree C,et al.Metformin's reverses fatty liver disease in obeseleptin-deficient mice [J].Nature Medicine,2000,6(8):998-1003
    [24] Soga M, Kishimoto Y, Kawamura Y, et al. Spontaneous development of hepatocellularcarcinomas in the FLS mice with hereditary fatty liver[J].Cancer Lett,2003,196(1):43-48
    [25] Shekhaw at PS,Yang H S,Bennett MJ,et al.Carnitine content and expression ofmitochondrial β-oxidation enzymes in placentas of wild-type (OCTN2+/+) and OCTN2Null (OCTN2-/-) mice [J].Pediatr Res,2004,56(3):323-328
    [26]王炳芳,朱韶杰,田培营.脂肪肝细胞模型的建立及其生物学特性[J].世界华人消化杂志,2007,15(35):3674-3677
    [1]陈卫星,刁国俊,蒋文娟,等.决明子对高胆固醇血症小鼠模型的影响[J].中草药,1991,22(2):72
    [2]张永华,李永峰,李敏娜.等.枳椇子水提取液治疗非酒精性脂肪性肝炎的实验研究[J].浙江中西医结合杂志,2009,19(1):12-14
    [3]李富.中西医结合治疗高脂血症脂肪肝疗效观察[J].实用中西医结合杂志,1994,13(2):62
    [4]尹镭,赵元昌,许瑞龄,等.茯苓对实验性肝硬变的治疗作用[J].山西医学院学报,1992,23(2):101-103
    [5]郭淑睿,曹永荣,高光英.郁金对实验性高脂血症动物血脂含量的影响[J].中医药研究,1998,14(3):32-33.
    [6]孙丽伟,黄妙珍.丹参对非酒精性脂肪肝大鼠血清MDA、SOD、TNF、Leptin的影响[J].浙江中医药大学学报,2007,31(6):696-698
    [7]刘国生,李莉,段玉光,等.山楂不同极性提取物对高脂血症大鼠血脂及血液流变性的影响[J].安徽中医学院学报,2008,27(1):38-40.
    [8]许峰,等.大黄、大黄素对内毒素刺激下大鼠肝巨噬细胞分泌细胞因子影响的动态观察[J].中国实验临床免疫学杂志,1996,8(5):41
    [9]王文健.降脂工号及11号方治疗高脂血症的比较观察[J].中国中西医结合杂志,1995,15(7):44
    [10]历有名,夏维新.脂肪肝现代诊疗[M].南京:江苏科学技术出版社.2003:223
    [11]张桂灵,石小枫,刘杞.真菌深黄被孢霉脂提物对实验性非酒精性脂肪肝的作用[J].中药药理与临床,2004,20(6):22
    [12]应力,姜春萌,王朝晖.甘正复方对大鼠非酒精性脂肪肝的影响[J],2006,14(1):30-33
    [13]卢明芳,王晓君,王蓉.软脉灵对非酒精性脂肪肝大鼠肝功能及血脂的影响[J].山东医药,2008,48(37):35-36
    [14]张朕华,张择生,李承达.薯蓣皂苷对大鼠非酒精性脂肪肝的干预作用[J].时珍国医国药,2012,23(5):1116-1117
    [15]姜玲玲,厉有名,黄伟,等.非酒精性脂肪肝及其危险因素调查[[Jl.中国公共卫生,2005,21(3):326-327
    [16]中华医学会肝脏病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病的诊断标准[J].中华肝脏病杂志,2003,11:73
    [17]中华医学会肝病学分会脂肪肝和酒精性肝病学组,非酒精性脂肪性肝病诊疗指南(2010年修订版)[J].胃肠病学和肝病学杂志,2010,19(6):483-487
    [18] Moreno Sanehez D.Pathogenesis of Primary nonaleoholic fatty liver disease. MedClin(Barc),2005,124(17):668-771
    [19] Day CP, James OF.Hepatic steatosis: Innocent bystander or guilty party?[J].Hepatology,1998,27:1463-1466
    [20] Samuel VT, Liu ZX,Qu X,etal.Mechanism of hepatic insulin resistantin non-alcoholicfatty liver disease[J]. J Biolchem,2004,279(31):32345-32353
    [21] DayCP.Pathogenesis of steatohePatitis.Best Practice and research.Clin Gastroenterol,2002.16:663-782
    [22] Ogawa W,Matozaki T, Kasuga M. Role of binding proteins to IRS-1in in-sulinsignalling[J]. Mol Cell Biochem,1998,182(1-2):13-22
    [23]范建高.脂肪肝与代谢综合症[M].国外医学·内分泌分册,2002,22(5):273-275
    [24] CollinsS, Kuhn CM, Petro AE.etal, Role of leptin in fot regultion [J]. Nature,1996,380:677
    [25]刘佃辛,王长龄,金宏.瘦素降低胆固醇作用的观察.解放军预防医学杂志,2000,18(6):452
    [26] Seufert J Kieffer TJ, Habener JF.Leptin inhibits insulin gene tran-scription and reverseshyperinsulinemia in leptin-deficient ob/obmice.M edical Sciences,1999,96:674-679
    [27] Seufert J,KiefferTJ,L eech CA,et al Leptin suppression of insulin secretion and geneexpression in hum an pancreatic islets Imp lications for the developm ent of adipogenicdia-betes mellitus[J].J C lin Endocrino M etab,1999,84(3):670
    [28] Faggion I R,Jones-Carson J Reed DA,etal.Leptin-deficient (ob/ob) mice are protectedfrom T cell-mediated hepatotoxicity:role of tum or necrosis factoralpha andIL-18.ProsN atlA cad SciSA,2000,97(5):2367
    [29] Piche T,Vandenbos F,Abakar-M ahamat A,et al.The severity of liver fibrosis isassociated with high leptin levels in chronic hepatitis.J Viral H epat,2004,11(1):91-96
    [30] Ribeiro PS,Cortez-Pinto H,Sola S,et al.Hepatocyte apoptosis,expression of deathreceptors,and activation of NF-kappaB in the liver of nonalcoholic and alcoholicsteatohepatitis patients. Am J Gastroentero1,2004,99(9):1708-17
    [31] Pessayre,D,Berson A,Fromenty B,etal.Mitoehondria in steatohePatitis,Semin LiverDis,2001,21:57-69
    [32] Duvnjak M,Leroti I,Barsi N,Tomasi V,Virovic Juki L,Velagic V.Pathogenesis andmanagementissues for non-alcoholic fatty liver disease. World J Gastroenterol2007,13:4539-4550
    [33] HOTAMISLIGIL G S, SHARGILL N S, SPIEGELMAN BM.Adipose expression oftumor ecrosis factor-alpha:direct role in obesity-linked insulin resistance[J]. Sci,1993,259:87-91
    [34]林克荣,杨慧莹.非酒精性脂肪肝患者血清肿瘤坏死因子-α、脂联素水平与胰岛素抵抗的相关性[J].世界华人消化杂志,2007,15(24):2613-2618
    [35] Hui JM,Hodge A, Farrell GC,etal.Beyond insulin resistance in NASH:TNF-alpha oradiponectin? Hepatology,2004,40(1):19-22
    [36] FERRE P. The biology of peroxisome proliferators-activated receptors: relationshipwith lipid metabolism and insulin sensitivity[J]. Diabetes,2004,53:43-50
    [37] EVERETT L,GALII A,CRABB D.The role of hepatic peroxisome proliferatorr-activated receptors(PPARs)in health and disease[J]. Liver,2000,20:191-199
    [38] Rurh M,Peter HJ.The metabolic syndrome and type2diabetes:role of the adipocyte.Curr Opin Lipidol,2003,14:549-553
    [39] Rao MS, Reddy JK.Peroxisomal beta-oxidation and steatohepatitis. Semin LiverDis,2001,21(1):43-55

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700