A rat model of hepatic veno-occlusive disease induced by the Gynura root water decoction
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摘要: 目的通过观察不同浓度土三七水煎剂所致的大鼠肝脏病理学变化,建立一种模拟临床患者服药所致肝小静脉闭塞病(HVOD)的动物模型。方法土三七2100 g水煎制成浓度为1.5 g/ml土三七生药煎剂,SD大鼠76只随机分为A、B、C、D四组,A、B、C组每组20只,分别以土三七水煎剂高(15 g.kg-1.d-1)、中(7.5 g.kg-1.d-1)、低(3.75 g.kg-1.d-1)浓度灌胃,D组16只以温开水灌胃作为对照,各组大鼠雌、雄各半。每日测量大鼠体重并记录异常表现,灌胃1周和2周后各组大鼠分别处死各半,肝脏标本行病理检查,HE及Masson染色,光镜下参照Deleve评分标准判定病变及严重程度。结果土三七高、中、低浓度组分别有83.3%(15/18)、75.0%(15/20)、40.0%(5/20)出现了肝小静脉闭塞病病理表现;相同剂量下雌性较雄性更易发病,雌、雄鼠造模成功率分别为79.3%(23/29)和41.3%(12/29)(P=0.003)。结论土三七水煎剂灌胃可以成功建立HVOD大鼠模型,剂量和大鼠性别与造模成功率直接相关。Abstract: Objective To study the pathological lesions of rat liver induced by the Gynura root water decoction, and establish a rat model for hepatic veno-occlusive disease (HVOD) .Methods 2100 gram Gynura root was prepared into the water decoction with the concentration of 1.5 g/ml.Group A, B and C with 20 SD rats were perfused intragastrically with the Gynura root water decoction with different concentrations of 15 g·kg-1·d-1, 7.5 g·kg-1·d-1 and 3.75 g·kg-1·d-1, respectively.Group D was perfused intragastrically with water which served as the controls.The ratio of male to female was 1:1 in every group.The body weights and symptoms were observed every day.Half of the rats from each group were killed and their liver samples were stained with H&E and Masson techniques after one week and two weeks of drug administration respectively.Results The pathological manifestations of HVOD were observed in the 15 rats of 18 (83.3%) in group A, 15 of 20 (75.0%) in group B and 5 of 20 (40.0%) in group C.With the same dose, the female rats were prone to HVOD.After re-grouping by gender, pathological manifestations of HVOD could be found in 23 of the 29 male rats and 12 of the 29 female rats (79.3% vs 41.3%, P=0.003) .Conclusion The rat HVOD model could be induced by the Gynura root water decoction successfully which was associated with the concentration and gender.
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Key words:
- disease models /
- animal /
- hepatic veno-occlusive disease
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[1]宋宇, 樊艳华.土三七所致肝小静脉闭塞病102例临床分析[J].临床肝胆病杂志, 2011, 27 (5) :496-499. [2]DeLeve LD, Mccuskey RS, Wang X, et al.Characterization of aReproducible Rat Model of Hepatic Veno-occlusive Disease[J].Hepatology, 1999, 29 (6) :1779-1791. [3]冀涛.MMP-9在土三七致肝窦阻塞综合征中的表达及意义[D].浙江:浙江大学, 2009. [4]高新生, 肖绍树, 贺降福.土三七生物碱成分分析及肝小静脉闭塞病小鼠模型建立[J].中国中西医结合消化杂志, 2006, 14 (5) :311-313. [5]Kaikita K, Fogo AB, Ma L, et al.Plasminogen activator inhibitor-1 deficiency prevents hypertension and vascular fibrosis in re-sponse to long-term nitric oxide synthase inhibition[J].Circula-tion, 2001, 104 (7) :839-844. [6]Smith LH, Dixon JD, Stringham JR, et al.Pivotal role of PAI-1in a murine model of hepatic vein thrombosis[J].Blood, 2006, 107 (1) :132-134. [7]Czauderna P, Chyczewski L, Lech K, et al.Experimental model of he-patic venoocclusive disease (VOD) caused by dactinomycin--pre-liminary report about hepatoprotective effect of amifostine[J].Med SciMonit, 2000, 6 (3) :446-453. [8]Epstein RB, Min KW, Anderson SL, et al.A canine model for he-patic venoocclusive disease[J].Transplantation, 1992, 54 (1) :12-16. [9]Miranda CL, Reed RL, Guengerich FP, et al.Role of cytochromeP450IIIA4 in the metabolism of the pyrrolizidine alkaloid sene-cionine in human liver[J].Carcinogenesis, 1991, 12 (3) :515-519. [10]Meibohm B, Beierle I, Derendorf H.How important are genderdifferences in pharmacokinetics[J].Clin Pharmacokinet, 2002, 41 (5) :329-342. [11]Yu AM, Fukamachi K, Krausz KW, et al.Potential Role for Hu-man Cytochrome P450 3A4 in Estradiol Homeostasis[J].Endocri-nology, 2005, 146 (7) :2911-2919. [12]Deleve LD, Wang X, Tsai J, et a1.Sinusoidal obstruction syn-drome (veno-occlusive disease) in the rat is prevented by matrixmetalloproteinase inhibition[J].Gastroenterology, 2003, 125 (3) :882-890. [13]Hoetzer GL, Maceneaney OJ, Irmiger HM, et al.Gender differencein circulating endothelial progenitor cell colony-forming capacityand migratory activity in middle-aged adults[J].Am J Cardiol, 2007, 99 (1) :46-48 [14]Strehlow K, Werner N, Berweiler J, et al.Estrogen increases bonemarrow derived endothelial progenitor cell production and diminishesneointima formation[J].Circulation, 2003, 107 (24) :3059-3065. [15]Heissig B, Hattori K, Dias S, et al.Recruitment of stem cell andprogenitor cells from the bone marrow niche requires MMP-9 medi-ated release of Kit-ligand[J].Cell, 2002, 109 (5) :625-637.
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