肝纤维化大鼠血清透明质酸、Ⅲ型前胶原、层粘连蛋白及羟脯氨酸水平与丹参、桃仁复方制剂的干预

Danshen and Taoren mixture for intervention of serum hyaluronic acid,precollagen Ⅲ,laminin and hydroxyproline in hepatic fibroblast model rats

目的:观察丹参、桃仁复方制剂对肝纤维化大鼠血清透明质酸、Ⅲ型前胶原、层粘连蛋白及羟脯氨酸水平的影响,并与复方鳖甲软肝片进行阳性药物对照。方法:实验于2004-04/12在成都中医药大学药理实验室完成。①70只SD大鼠随机取10只为空白对照组,其余60只大鼠皮下注射CCl4,同时给予高脂饲料和体积分数为0.2的乙醇喂养6周建立肝纤维化大鼠模型,造模成功的50只大鼠按性别、体质量随机分为模型组,丹参和桃仁复方制剂高、中、低剂量组,复方鳖甲软肝片组5组,每组10只。②空白对照组和模型组灌胃给予蒸馏水0.1mL/kg,丹参和桃仁复方制剂高、中、低剂量组灌胃给予6,3,1.5g/kg丹参和桃仁复方制剂(主要成分为丹参、桃仁、白芍、黄芪、柴胡、汉防己、冬虫夏草等),复方鳖甲软肝片组灌胃给予1g/kg复方鳖甲软肝片,1次/d,连续4周。③末次给药后24h,髂外静脉取血,测定血清透明质酸、Ⅲ型前胶原、层粘连蛋白及羟脯氨酸水平。结果:60只大鼠进入结果分析。①透明质酸质量浓度:模型组比空白对照组增高了256.72%,丹参、桃仁复方制剂高剂量组比模型组降低39.46%(P<0.05)。②层粘连蛋白质量浓度:模型组比空白对照组增高了100.73%,丹参、桃仁复方制剂高、低剂量组比模型组降低18.29%,21.99%(P<0.05)。③羟脯氨酸浓度:模型组比空白对照组增高了315.75%,丹参、桃仁复方制剂高、中剂量组比模型组降低34.26%,46.65%(P均<0.01)。④复方鳖甲软肝片组大鼠血清Ⅲ型前胶原、层粘连蛋白和羟脯氨酸浓度比模型组分别降低20.99%,27.50%,22.91%。结论:丹参、桃仁复方制剂能降低CCl4复合因素致纤维化模型大鼠血清透明质酸、层粘连蛋白和羟脯氨酸水平,其效果优于复方鳖甲软肝片。

AIM： To explore the effects of Danshen and Taoren mixture on hyaluronic acid （HA）, precollagen （PC）Ⅲ, laminin （LN） and hydroxyproline （Hyp） in the blood serum of hepatic fibroblast （HF） model rats, and compare with the effect of Compound Biejia Ruangan Tablet （CBT）. METHODS： Experiments were done in Pharmacology Laboratory of Chengdu University of Traditional Chinese Medicine during April and December 2004. ①Seventy SD rats were grouped in six groups basing on sex and weight. Ten rats in blank group, whereas the other rats were injected hypodermically with CCL4 and feed with the high fat diet and 20% ethyl alcohol for six weeks to established HF models. Excluding 10 unsuccessful models, the treated rats were assigned into model group, Danshen and Taoren mixture group of high, middle, low dose, CBT group, with 10 rats in each.②Rats of blank group and model group were injected with 0.1 mL/kg distilled water intragastrically, and those of three mixture groups were treated with 6, 3, 1.5 g/kg Danshen and Taoren mixture respectively （essential components included Danshen, Taoren, white peony alba, milkvetch root, bupleurum root, Stephania tetrandra, Chinese caterpillar fungus and so on）. CBT of 1 g/kg was administrated in CBT group once daily for four weeks.③At 24 hours after the last administration, the external lilac vein blood was sampled to observe the contents of HA, PCⅢ, LN and Hyp in the blood serum. RESULTS： All 60 rats were involved in the result analysis.①Contents of HA in model group were increased by 256.72% compared with the blank group, and those of high dose mixture group was decreased by 39.46% compared with model group （P 〈 0.05）. ②Contents of LN in model group were increased by 100.73% compared with the blank group, and those of high and low dose mixture groups were decreased by 18.29% and 21.99%, respectively compared with model group （P 〈 0.05）. ③Contents of Hyp in model group were increased by 315.75% compared with the blank group, and those of high and moderate dose mixture group were decreased by 34.26% and 46.65% respectively compared with the model group （P 〈 0.05）.④The contents of Pcm, LN and Hyp were decreased in CBT group compared with model group （20.99%, 27.50%, 22.91%）. CONCLUSION： Danshen and Taoren mixture can decrease the contents of HA, LN and Hyp in the blood serum of HF model rats induced by CCL4, and the effect is superior to that of CBT.