红花茯苓提取液防治四氯化碳性大鼠肝纤维化的作用

Effect of honghua fuling extract liquid on hepatic fibrosis of rats induced by carbon tetrachloride

目的:观察四氯化碳诱导的大鼠肝损害的特点,并分析中药复方红花茯苓提取液对其防治作用。方法:实验于2003-03/2005-09在广东医学院实验动物中心、药理研究室和中心实验室完成。选用60只SPF级SD大鼠,随机分为6组,即正常对照组,模型对照组,阳性对照组,红花茯苓提取液生药0.5kg/L组,1kg/L组,2kg/L组,每组10只,雌雄各半。红花茯苓提取液3种剂量制剂由广东医学院科技医药开发中心提供,为红花、茯苓、甘草等中药按照常规中药水提法,经过3次提取最后浓缩所需的剂量含生药2kg/L,然后用双蒸水稀释得到1kg/L和0.5kg/L的所需剂量。除正常对照组外,其余各组予600g/L四氯化碳花生油,按3mL/kg皮下注射,首剂加倍,3d注射1次,连续7周,造成大鼠慢性损伤性肝纤维化模型。同时观察红花茯苓提取液2kg/L、1kg/L、0.5kg/L对大鼠肝组织病理变化、血清透明质酸、血清丙氨酸氨基转移酶、天冬氨酸氨基转氨酶、总蛋白和白蛋白以及内脏器官质量的影响,并与秋水仙碱进行了比较,评价红花茯苓提取液对大鼠四氯化碳性肝损害的防治作用及其特点。结果:纳入动物60只,全部进入结果分析。①肝脏变化:模型组肝脏指数比正常组增加2.4倍(P<0.01),肝脏细胞明显变性坏死,纤维组织明显增生,正常对照组肝脏未见纤维增生,模型组肝纤维化程度达100%(P<0.01),秋水仙碱可明显减轻肝纤维化程度,红花茯苓提取液2kg/L、1kg/L、0.5kg/L也具有明显的抗肝纤维化作用(P<0.05),与秋水仙组相比差异不具有显著意义,但肝脏指数比模型组分别减轻1.4倍、1.7倍和2.3倍(P<0.05)。②血清指标变化:秋水仙组透明质酸的含量与模型组相比,下降了3倍(P<0.05),红花茯苓提取液2kg/L、1kg/L、0.5kg/L组分别下降2.2倍,2.3倍和2.6倍;红花茯苓提取液2kg/L、1kg/L、0.5kg/L丙氨酸氨基转移酶的活性与模型组相比,分别降低1.6倍、1.5倍和2倍,天冬氨酸氨基转氨酶活性也明显下降(P<0.05),血清白蛋白的含量升高,其中0.5kg/L组比模型组增1倍(P<0.05)。③门静脉压变化:模型组门静脉压比正常组升高,但是差异无显著意义,各组的门静脉压差异无显著性(P>0.05)。结论:红花茯苓提取液可有效预防大鼠四氯化碳性肝损害后肝纤维化,并能降低转氨酶和升高蛋白含量。

AIM： To study the character of hepatic damage induced by carbon tetrachlofide and analyze the effect of compound honghua titling extract liquid on its prevention and cure. METHODS： The experiment was completed in the Experiment Animal Center, Pharmacological Laboratory and Central Laboratory of Guangdong Medical College from March 2003 to September 2005. Sixty SD rats of SPF grade were randomly divided into 6 groups： normal control group, model control group, positive control group, compound honghua tiding extract liquid 0.5 kg/L group, 1 kg/L group and 2 kg/L group with 10 of either gender in each group. Three dosages of compound honghuafuling extract liquid were provided by Technological Medicament Empelder Center of Guangdong Medical College. The compound was used honghua, titling and gancaotopick-up3timestogetthedoseof 2 kg/l, twicedistilledwatertodilute to get the dose of 0.5 kg/L and 1 kg/L.All the animals were given 600 g/L carbon tetrachloride arachis oil on the basis of 3 mL/kg subcutaneous injection once per 3 days for 7 weeks for the model of hepatic fibrosis except the control group. And the effects of compound honghua fuling extract liquid on histological change, serum hyaluronic acid, serum alanine aminotransferase, asparagic acid transamlnase, total protein （TP）, albumin （Alb） and weigh of visceras in hepatic tissue were observed in each dosage group. All the results were compared with colchicines to estimate the effect and character of compound honghuafuling extract liquid on preventing and curing hepatic damage induced by carbon tetrachloride. RESULTS： Totally 60 rats entered the final analysis. ① Changes of liver： Liver index in model group was increased 2.4 times than that in control group （P 〈 0.01）, and histopathological showed that most of hepatic cells in model group were degenerated seriously and fibrin tissue was proliferated clearly, But fiber proliferation was not observed in normal control group and hepatic fibrosis was reached 100% （P 〈 0.05）. There was not significantly different from that in crocus group. Hepatic indexes decreased 1.4, 1.7 and 2.3 times as compared with those in model group respectively （P 〈 0.05）. ② Changes of serum indexes： Content of hyaluronic acid in crocus group was decreased 3 times as compared with that in model group （P 〈 0,01）, 2.2, 2.3 and 2.6 times in compound honghuafuling extract liquid 0.5 kg/L 1 kg/L and 2 kg/L groups respectively; activities of Alanine aminotransferase were decreased 1.6, 1.5 and 2 times as compared with those in model group respectively; activity of asparagic acid transaminase was obviously decreased （P 〈 0.05）; content of albumin was increased, especially that in 0.5 kg/L compound honghua fuling extract liquid group was 1 time than that in model group （P 〈 0.05）. ③ Change of portal vein pressure： The portal vein pressure in model group was higher than that in normal group, but there was no significant difference, and there were no significant differences among the six groups （P 〉 0.05）. CONCLUSION： Compound honghua fuling extract liquid can prevent hepatic fibrosis after liver damage induced by carbon tetrachloride, decrease content of transaminase, and increase content of protein in rats.