蝙蝠葛酚性碱对大鼠肝纤维化的影响及其机制探讨  

Effect of Phenolic Alkaloids of Menispermum Dauricum on Hepatic Fibrosis in Rats and Their Mechanism

作　　者：费洪新[1] 张英博[1] 张晓杰[1] 柏青杨[1] 

机构地区：[1]齐齐哈尔医学院,黑龙江齐齐哈尔161006

出　　处：《中国实验方剂学杂志》2016年第18期106-111,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81173576);黑龙江省教育厅项目(12531788;12521624);黑龙江省自然科学基金项目(H201354);黑龙江省科技攻关项目(PC13S06)

摘　　要：目的:观察蝙蝠葛酚性碱(PAMD)对四氯化碳(CCl4)诱导大鼠肝纤维化的影响,并探讨其作用机制。方法:SD大鼠随机分成正常组,模型组,秋水仙碱组(1 mg·kg-1),PAMD高、中、低剂量组(25,12.5,6.25 mg·kg-1)。采用40%CCl4(1m L·kg-1)ip诱导肝纤维化模型大鼠。所有大鼠给予等体积药物或生理盐水ig,持续30 d。放射免疫法检测血清透明质酸(HA),层粘连蛋白(LN),Ⅲ型前胶原(PCⅢ)和Ⅳ型胶原(CⅣ)水平。生化分析法检测血清丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST),总蛋白(TP)和白蛋白(ALB)水平。酶联免疫吸附测定(ELISA)法检测肝脏中转化生长因子-β1(TGF-β1)和肿瘤坏死因子-α(TNF-α)水平。电子显微镜观察大鼠肝组织镜下形态结构,计算肝和脾脏脏器指数。结果:与正常组比较,模型组大鼠血清HA,LN,PCⅢ,CIV,ALT和AST明显增加(P<0.05),TP和ALB明显降低(P<0.05),肝组织TGF-β1和TNF-α水平明显升高(P<0.05),肝脏病理纤维化大鼠明显加重,肝脏和脾脏脏器指数明显升高(P<0.05);与模型组比较,PAMD高、中剂量组大鼠血清HA,LN,PCⅢ,CIV,ALT和AST明显降低(P<0.05),TP和ALB明显升高(P<0.05),肝组织TGF-β1和TNF-α水平明显降低(P<0.05),肝脏病理纤维化大鼠明显减轻,肝脏和脾脏脏器指数明显降低(P<0.05)。结论:PAMD能有效减轻CCl4诱导肝纤维化大鼠的肝脏损伤,降低肝纤维化程度,其机制与抑制肝脏TGF-β1和TNF-α蛋白表达有关。Objective： To observe the effects of phenolic alkaloids of Menispermum dauricum（ PAMD）on CCl4 induce hepatic fibrosisin rats and investigate its action mechanism. Method： Sprague-Dawley rats were randomly divided into normal group,model group,colchicine group（ 1 mg·kg- 1）,PAMD high-dose group（ 25mg·kg- 1）. PAMD medial-dose group（ 12. 5 mg·kg- 1） and PAMD low-dose group（ 6. 25 mg·kg- 1）.Intraperitoneal injection of 40% CCl4（ 1 m L·kg- 1） was used to induce hepatic fibrosis models in the rats. All the rats received the same volume of drugs or normal saline by intragastric administration for 30 days. The radioimmunoassay was used to determine the levels of hyaluronic acid（ HA）,laminin（ LN）,procollagen Ⅲ（ PCⅢ） and collagen Ⅳ（ C Ⅳ） in serum. The biochemical analysis was used to determine the levels of alanine aminotransferase（ ALT）,aspartate aminotransferase（ AST）,total protein（ TP） and album protein（ ALB） in serum. The enzyme-linked immuno sorbent assay（ ELISA） was applied to detect the levels of transforming growth factor-β1（ TGF-β1） and tumor necrosis factor-α（ TNF-α） in the liver tissues. Morphology of liver tissues wasobserved by optical electron microscopy,and the organ coefficients of liver and spleen were calculated then.Result： As compared with the normal group,the levels of HA,LN,PC Ⅲ,CIV,ALT and AST in serum were significantly increased in the serum of model group（ P 0. 05）; levels of TP and ALB in serum were significantly decreased（ P 0. 05）; levels of TGF-β1and TNF-α in the liver tissues were significantly increased（ P 0. 05）;the liver pathological fibrosis was aggravated significantly; organ coefficients of liver and spleen were significantly increased（ P 0. 05）. As compared with the model group,the levels of HA,LN,PC-Ⅲ,CIV,ALT and AST in serum were significantly decreased in PAMD high-dose group and PAMD medial-dose group（ P 0. 05）; the levels of TP and ALB in serum were significantly inc

关 键 词：蝙蝠葛酚性碱 肝纤维化 四氯化碳 转化生长因子-Β1 肿瘤坏死因子-Α 

分 类 号：R285.5[医药卫生—中药学]