背景:水飞蓟宾(素)可产生抗自由基活性、抗脂质过氧化、抗脂氧酶、抗还原性谷胱甘肽排空、抗肿瘤以及降血脂等广泛的药理效应.在临床上,水飞蓟宾也常用于酒精性肝病的治疗.目的:探讨水飞蓟宾对大鼠酒精性脂肪肝作用的药理学机制.设计:随机对照实验.单位:广州市中医医院.材料:实验于2003-08/10在广东省药物研究所无特殊病原菌级动物实验室完成,选用无特殊病原菌级SD大鼠57只,雌雄各半,体质量(150±10)g.益肝灵片主要成份为水飞蓟宾,38.5 mg/片,湖南省株洲市制药三厂生产.方法:在57只SD大鼠中随机选出18只作为正常对照组,给予生理盐水灌胃,饮用蒸馏水代替乙醇,普通饲料喂养10周.其余大鼠自由饮用100 mL/L乙醇,加高脂高热量饲料喂养6周,构建大鼠酒精性脂肪肝模型,经相关指标检测确定模型成立.将剩余大鼠随机分成模型对照组18只和水飞蓟宾组21只,模型对照组给予蒸馏水灌胃,水飞蓟宾组给予水飞蓟宾100 mg/kg.同时继续给予100 mL/L乙醇和高营养饲料,4周后在麻醉状态下处死大鼠,取大鼠肝块进行病理观察,测定三酰甘油、超氧化物歧化酶、还原性谷胱甘肽和丙二醛水平.主要观察指标:大鼠血清中天冬氨酸氨基转移酶、丙氨酸氨基转移酶、碱性磷酸酶活性和三酰甘油、胆固醇、低密度脂蛋白-胆固醇、高密度脂蛋白-胆固醇、大鼠肿瘤坏死因子α、大鼠转化生长因子β1的含量.结果:57只无特殊病原菌级SD大鼠全部纳入结果分析.水飞蓟宾能够抑制病鼠血清天冬氨酸氨基转移酶、丙氨酸氨基转移酶、碱性磷酸酶活性(2 550.5±400.1),(533.4±100.0),(2 217.1±750.2)nkat/L,与模型组比较(3 600.7±666.8),(800.2±100.0),(2 900.6±1 333.6)nkat/L,差异有显著性意义(P＜0.05～0.01);水飞蓟宾组三酰甘油、低密度脂蛋白-胆固醇、大鼠肿瘤坏死因子α和大鼠转化生长因子β1含量(1.8±0.8),(0.17±0.04),(6.66±1.38),(24.1±4.1)mmol/L明显低于模型组(2.8±1.4),(0.20±0.05),(7.81±1.06),(28.8±6.3)mmol/L,两组比较差异有显著性(P＜0.05～0.01);水飞蓟宾能够提高高密度脂蛋白-胆固醇含量;降低肝匀浆三酰甘油和丙二醛含量(P＜0.05～0.01),增强超氧化物歧化酶活性以及改善肝细胞水变性和脂肪变性(P＜0.01),但对还原型谷胱甘肽的含量则未见明显改变(P＞0.05).结论:水飞蓟素阻止大鼠酒精性脂肪肝形成,其作用机制包括抗氧化、清除自由基代谢产物,抑制脂质过氧化反应,调血脂、减少脂肪在肝脏的沉积,抗免疫性炎症和抗增殖.
揹景:水飛薊賓(素)可產生抗自由基活性、抗脂質過氧化、抗脂氧酶、抗還原性穀胱甘肽排空、抗腫瘤以及降血脂等廣汎的藥理效應.在臨床上,水飛薊賓也常用于酒精性肝病的治療.目的:探討水飛薊賓對大鼠酒精性脂肪肝作用的藥理學機製.設計:隨機對照實驗.單位:廣州市中醫醫院.材料:實驗于2003-08/10在廣東省藥物研究所無特殊病原菌級動物實驗室完成,選用無特殊病原菌級SD大鼠57隻,雌雄各半,體質量(150±10)g.益肝靈片主要成份為水飛薊賓,38.5 mg/片,湖南省株洲市製藥三廠生產.方法:在57隻SD大鼠中隨機選齣18隻作為正常對照組,給予生理鹽水灌胃,飲用蒸餾水代替乙醇,普通飼料餵養10週.其餘大鼠自由飲用100 mL/L乙醇,加高脂高熱量飼料餵養6週,構建大鼠酒精性脂肪肝模型,經相關指標檢測確定模型成立.將剩餘大鼠隨機分成模型對照組18隻和水飛薊賓組21隻,模型對照組給予蒸餾水灌胃,水飛薊賓組給予水飛薊賓100 mg/kg.同時繼續給予100 mL/L乙醇和高營養飼料,4週後在痳醉狀態下處死大鼠,取大鼠肝塊進行病理觀察,測定三酰甘油、超氧化物歧化酶、還原性穀胱甘肽和丙二醛水平.主要觀察指標:大鼠血清中天鼕氨痠氨基轉移酶、丙氨痠氨基轉移酶、堿性燐痠酶活性和三酰甘油、膽固醇、低密度脂蛋白-膽固醇、高密度脂蛋白-膽固醇、大鼠腫瘤壞死因子α、大鼠轉化生長因子β1的含量.結果:57隻無特殊病原菌級SD大鼠全部納入結果分析.水飛薊賓能夠抑製病鼠血清天鼕氨痠氨基轉移酶、丙氨痠氨基轉移酶、堿性燐痠酶活性(2 550.5±400.1),(533.4±100.0),(2 217.1±750.2)nkat/L,與模型組比較(3 600.7±666.8),(800.2±100.0),(2 900.6±1 333.6)nkat/L,差異有顯著性意義(P＜0.05～0.01);水飛薊賓組三酰甘油、低密度脂蛋白-膽固醇、大鼠腫瘤壞死因子α和大鼠轉化生長因子β1含量(1.8±0.8),(0.17±0.04),(6.66±1.38),(24.1±4.1)mmol/L明顯低于模型組(2.8±1.4),(0.20±0.05),(7.81±1.06),(28.8±6.3)mmol/L,兩組比較差異有顯著性(P＜0.05～0.01);水飛薊賓能夠提高高密度脂蛋白-膽固醇含量;降低肝勻漿三酰甘油和丙二醛含量(P＜0.05～0.01),增彊超氧化物歧化酶活性以及改善肝細胞水變性和脂肪變性(P＜0.01),但對還原型穀胱甘肽的含量則未見明顯改變(P＞0.05).結論:水飛薊素阻止大鼠酒精性脂肪肝形成,其作用機製包括抗氧化、清除自由基代謝產物,抑製脂質過氧化反應,調血脂、減少脂肪在肝髒的沉積,抗免疫性炎癥和抗增殖.
배경:수비계빈(소)가산생항자유기활성、항지질과양화、항지양매、항환원성곡광감태배공、항종류이급강혈지등엄범적약리효응.재림상상,수비계빈야상용우주정성간병적치료.목적:탐토수비계빈대대서주정성지방간작용적약이학궤제.설계:수궤대조실험.단위:엄주시중의의원.재료:실험우2003-08/10재광동성약물연구소무특수병원균급동물실험실완성,선용무특수병원균급SD대서57지,자웅각반,체질량(150±10)g.익간령편주요성빈위수비계빈,38.5 mg/편,호남성주주시제약삼엄생산.방법:재57지SD대서중수궤선출18지작위정상대조조,급여생리염수관위,음용증류수대체을순,보통사료위양10주.기여대서자유음용100 mL/L을순,가고지고열량사료위양6주,구건대서주정성지방간모형,경상관지표검측학정모형성립.장잉여대서수궤분성모형대조조18지화수비계빈조21지,모형대조조급여증류수관위,수비계빈조급여수비계빈100 mg/kg.동시계속급여100 mL/L을순화고영양사료,4주후재마취상태하처사대서,취대서간괴진행병리관찰,측정삼선감유、초양화물기화매、환원성곡광감태화병이철수평.주요관찰지표:대서혈청중천동안산안기전이매、병안산안기전이매、감성린산매활성화삼선감유、담고순、저밀도지단백-담고순、고밀도지단백-담고순、대서종류배사인자α、대서전화생장인자β1적함량.결과:57지무특수병원균급SD대서전부납입결과분석.수비계빈능구억제병서혈청천동안산안기전이매、병안산안기전이매、감성린산매활성(2 550.5±400.1),(533.4±100.0),(2 217.1±750.2)nkat/L,여모형조비교(3 600.7±666.8),(800.2±100.0),(2 900.6±1 333.6)nkat/L,차이유현저성의의(P＜0.05～0.01);수비계빈조삼선감유、저밀도지단백-담고순、대서종류배사인자α화대서전화생장인자β1함량(1.8±0.8),(0.17±0.04),(6.66±1.38),(24.1±4.1)mmol/L명현저우모형조(2.8±1.4),(0.20±0.05),(7.81±1.06),(28.8±6.3)mmol/L,량조비교차이유현저성(P＜0.05～0.01);수비계빈능구제고고밀도지단백-담고순함량;강저간균장삼선감유화병이철함량(P＜0.05～0.01),증강초양화물기화매활성이급개선간세포수변성화지방변성(P＜0.01),단대환원형곡광감태적함량칙미견명현개변(P＞0.05).결론:수비계소조지대서주정성지방간형성,기작용궤제포괄항양화、청제자유기대사산물,억제지질과양화반응,조혈지、감소지방재간장적침적,항면역성염증화항증식.
BACKGROUND: Silibinin has broad pharmaceutical effects, such as anti-free radicals, anti-lipid peroxidation, anti-lipoid oxidase, anti-glutathione (GSH) depletion, anti-neoplastic and serum lipid-lowering effects. Clinically, silibinin is often used in treating alcoholic liver disease.
OBJECTIVE: To investigate the pharmacological mechanism of silibinin for alcoholic fatty liver in rats.
DESIGN: Randomized and controlled study.SETTING: Guangzhou Hospital of Traditional Chinese Medicine.MATERIALS: The experiment was conducted at the Animal Experimental Laboratory of Guangdong Pharmaceutical Institute from August to October 2003. Totally 57 SD rats, without unusual bacteria, weighting (150±10)g and of either gender, were selected. Yiganling tablets containing 38.5 mg silibinin were produced by Zhuzhou No.3 Pharmaceutical Factory (Batch No. 20020808).METHODS: Among the 57 SD rats, 18 rats were regarded as normal control group. Rats in normal control group were administered with normal saline by gavage, and fed with normal food and distilled water in place of alcohol for 10 weeks. Rats in model group and silibinin group were fed with high-calorie food and 100 mL/L alcohol for 6 weeks to establish model of rat alcoholic fatty liver. The other rats were divided into model control group (n=18) and silibinin group (n=21). Rats in model control group were treated with distilled water while those in silibinin group were treated with 100 mg/kg silibinin. Meanwhile, 100 mL/L ethanol and hyperalimentation feed were given for 4 weeks. After animals were killed, TG, SOD, GSH and MDA levels were measured with liver suspension.MAIN OUTCOME MEASURES: Contents of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), tumor necrosis factor (TNF)-α , and transforming growth factor (TGF)-β1.RESULTS: All the 57 rats entered the final analysis. Silibinin could inhibit the activities of serum AST, ALT and AKP [(2 550.5±400.1), (533.4±100.0), (2 217.1±750.2)nkat/L], and the differences were significant as compared with those in model control group [(3 600.7±666.8), (800.2±100.0), (2 900.6±1 333.6) nkat/L, P ＜ 0.05-0.01]. Contents of TG, LDL-C, TNF-α and TGF-β1 in silibinin group [(1.8±0.8), (0.17±0.04), (6.66±1.38), (24.1±4.1) mmol/L] were lower than those in model group [(2.8±1.4), (0.20±0.05), (7.81±1.06), (28.8±6.3) mmol/L] with significant differences (P ＜ 0.05-0.01). Silibinin could increase the content of HDL-C but decrease the contents of TG and MDA (P ＜ 0.05-0.01), and improve SOD activity as well as hepatocyte and fatty degeneration (P ＜ 0.01).However, it had no obvious effect on the content of reduced estathion (P ＞ 0.05).CONCLUSION: Silibinin can inhibitthe formation of alcoholic fatty liver in rats. The pharmacological mechanism of silibinin may involve anti-oxidation, removing free radicals, inhibiting lipid peroxidation, regulating blood lipid component, reducing fatty sediment in liver, and anti-immunoinflammation and anti-hyperplasia effects.
