目的探讨蒿鳖养阴软坚方对牛血清白蛋白(BSA)免疫性肝纤维化大鼠的治疗作用。方法以18 mg/mL BSA与等体积的弗氏不完全佐剂混悬液足跖皮下多点注射5次免疫大鼠后,尾静脉攻击注射BSA生理盐水(每次2 mg/0.4 mL递增至3.4 mg/0.4 mL)15次,每周2次,制备肝纤维化模型;按体质量随机区组法分为模型组,蒿鳖养阴软坚方高、中、低剂量(8.2、2.59、0.82 g/kg,2.59 g/kg为临床等效剂量)组,复方鳖甲软肝片组,秋水仙碱组,各治疗组均于造模结束后ig给药(1 mL/100 g),每日1次,连续2个月,对照组和模型组分别ig等体积蒸馏水。酶谱法检测肝组织基质金属蛋白酶-2和-9(MMP-2、MMP-9),荧光法测定血清丙二醛(MDA),放免法检测血清透明质酸(HA)、层黏连蛋白(LN)、Ⅳ型胶原(Ⅳ-C)、Ⅲ型前胶原(PCⅢ)。结果蒿鳖养阴软坚方各剂量均能显著降低肝组织羟脯氨酸(Hyp)、MMP-2及MMP-9、肝纤维化程度、血清HA、LN、Ⅳ-C水平(P<0.05),其高、中剂量能明显降低血清MDA水平(P<0.05)。结论蒿鳖养阴软坚方对BSA免疫性肝纤维化大鼠具有治疗作用,抗脂质过氧化与降低MMP-2及MMP-9为其部分作用机制。

Objective To explore the therapeutic effect of Haobie Yangyin Ruanjian Prescription(HYRP) on immunity hepatic fibrosis rat caused by bovine serumalbumin(BSA) immunologic injury.Methods Ten rats were taken randomly as normal control,others were immunologically sc injected at several points of foot pad with BSA 18 mg/mL suspended with Freund′s incomplete adjuvant for 5 times,then BSA in NS(2 mg/0.4 mL gradually increased to 3.4 mg/0.4 mL) was injected into tail vein for 15 times,two times per week,hepatic fibrosis was induced successfully.After that the rats were divided by randomized block of body weight into model control,high(8.2 g/kg),middle(2.59 g/kg,equivalency to clinical therapeutic dose),and low(0.82 g/kg) dose groups of HYRP,compound recipe of Biejia Ruangan Tablet group,colchine group,and then ig administed corresponding drugs(1 mL/100 g) after model established,once a day for 2 months;While normal control and model control were given distilled water(1 mL/100 g) instead.Matrix metalloproteinase-2,-9(MMP-2 and MMP-9) in liver were determined with gelatin zymography,serum malondialdehyde(MDA) with fluorospectrophotometry,serum hyaluronic acid(HA),laminin(LN),collegen type IV(IV-C) and precollagen type Ⅲ(PCⅢ) with radioimmunoassay.Results Groups of 0.82,2.59,and 8.2 g/kg of HYRP could reduce the level of hepatic hydroxyproline(Hyp),MMP-2,MMP-9,hepatic fibrosis degree,serum HA,LN,and IV-C significantly(P0.05),2.59 and 8.2 g/kg groups of HYRP could lower MDA remarkably(P0.05).Conclusion HYRP has therapeutic effect on hepatic fibrosis rat caused by BSA immunologic injury,one of its mechanisms may be anti-peroxidation of lipid and decrease in MMP-2 and MMP-9.

国家自然科学基金面上项目(30772856);天津市应用基础研究计划重点资助项目(06YFJZJC02900)