氧化苦参碱防治半乳糖胺诱导大鼠肝纤维化的实验研究

Prophylactic and therapeutic effect of oxymatrine on D-galactosamine-induced rat liver fibrosis

目的 观察氧化苫参碱(oxymatrine,OM)预防及治疗大鼠肝纤维化的疗效并探讨其作用机制。方法 采用半乳糖胺诱导的大鼠肝纤维化模型,观察OM(90mg/kg)干预前后血及肝组织生物化学、羟脯氨酸含量、TGF β_1 mRNA表达水平及病理组织学改变。结果 OM干预组肝组织羟脯氨酸含量 (μg/mg)较模型组显著下降(预防观察组为0.50±0.11和0.99±0.14,t=8.366,P＜0.01;治疗观察组为0.44±0.04和0.70±0.06,t=9.839,P＜0.01);与模型组比较,干预组血清ALT、AST亦显著下降(P＜0.01);病理组织学显示干预组较模型组 Ⅰ、Ⅲ型胶原沉积减少,纤维间隔纤细,数量减少;干预织肝组织匀浆内超氧化物歧化酶活性(NU/mg)较模型组升高(预防观察组为149.81±15.28和95.22±16.33,t=7.309,P＜0.01;治疗观察组为157.68±19.54和119.88±14.94,t=4.348,P＜0.01), 而丙二醛(nmol/mg)低于模型组(预防观察组为2.06±0.17和4.57±0.37,t=17.529,P＜0.01;治疗观察组为1.76±0.24和3.10±0.17,t=12.697,P＜0.01);PT-PCR显示干预组TGF β_1 mRNA表达水平降低(预防观察组为0.21±0.01和0.50±0.01,t-48.665,P＜0.01;治疗观察组为0.18±0.02和0.38±0.01,t=22.464,P＜0.01)。结论 氧化苫参碱对半乳糖胺诱导的肝纤维化有预防及治疗作用。

ve To investigate the prophylactic and therapeutic effect of oxymatrine on experimental liverfibrosis and to reveal its mechanism. Methods By establishing D- galactosamine-induced rat liver fibrosis model, we ob-served the effect of oxymatrine on serum and tissue biochemical indexes, content of liver hydroxyline, expression of TGFβ_lmRNA and changes of tissue pathology. Results There was a decline of liver hydroxyline and serum AST and ALT inoxymatrine group compared to those of the D-GalN group. The hydroxyline content in oxymatrine pretreatment group was(0.50±0.1l)μg/mg compared with (0.99±0.l4)μg/mg in D-GalN group (t=8.366, P<0.0l ). The content in oxymatrinetreatment group was (0.44±0.04)μg/mg compared with 0.70±0.06 in D-GalN group (t=9.839. P<0.0l ). The SOD activitywas (l49.8l±15.28)NU/mg in oxymatrine pretreatment group and (95.22±l6.33)NU/mg in the model group (t=7.309, P<0.0l ); (l57.68±l9.54) NU/mg in the treatment group compared with (ll9.88±l4.94) NU/mg in the model group (t=4.348. P<0.0l). MDA in the pretreatment group was (2.06±0.l7) nmol/mg, lower than (4.57±0.37) nmol/mg in the mode1 group(t=l7.529. P<0.01 ). In the treatment group. it was (l.76±0.24) nmol/mg, lower than (3.l0±0.17) nmol/mg in the modelgroup (t=12.697, P<0.0l ). TGFβ_l mRNA reduced in the pretreatment and treatment groups as compared with that in themodel group (0.2l±0.01 vs 0.50±0.0l, t=48.665, P<0.0l; 0.18±0.02 vs 0.38±0.01, t=22.464. P<0.0l). Electron micros-copy showed that oxymatrine group had milder hepatocyte degeneration and less fibrosis accumulation than did the modelgroup. Microscopy revealed wide septa expansion from the portal area to the central venous, piecemeal and confluent necro-sis and pseudo-nodular formation in part of the lobular in the model group. While in oxymatrine group these lesions weremuch improved. Conclusions Oxymatrine shows prophylactic and therapeutic effect in D-galactosamine induced rat liverfibrosis. This is partly by protecting hepatoc-yte and suppressing fibrosis accumulation through anti-lipoperoxidation.