丹参滴丸对CCl4诱导的大鼠肝纤维化的影响及其作用机制

目的 观察丹参滴丸对CCl4致大鼠肝纤维化的保护作用,并探讨其作用机制.方法 除对照组外,其余各组大鼠用CCl4复合因素法诱导肝纤维化大鼠模型,丹参滴丸各组同时ig给予丹参滴丸700、350、175 mg/kg,阳性对照组给予扶正化瘀胶囊1 500 mg/kg,每天给药1次,连续给药7周,正常大鼠给予蒸馏水作为对照组.测定各组大鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、N-乙酰-β-D-氨基葡萄糖苷酶(NAG)的活性及总蛋白(TP)、白蛋白(ALB)、Ⅳ型胶原的水平;测定肝组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)和羟脯氨酸(Hyp)的量;HE和Masson染色观察肝组织病理形态学改变;免疫组化法检测α-平滑肌肌动蛋白(α-SMA)的表达.结果 丹参滴丸能明显抑制肝纤维化大鼠血清中ALT、AST、NAG活性的升高,降低Ⅳ型胶原的量,增加TP和ALB的量;降低肝组织中Hyp和MDA的量,提高SOD的活性,抑制胶原纤维的增加,亦能降低α-SMA的表达.结论 丹参滴丸有明显的抗肝纤维化作用,其作用机制与其抗脂质过氧化、抑制胶原纤维的增加及降低α-SMA的表达等密切相关.

Effect of Danshen Dropping Pills on hepatic fibrosis in rats induced by carbon tetrachlotide and its mechanism

Objective To study the protective effect of Danshen Dropping Pills(DDPs) on hepatic fibrosis in rats induced by carbon tetrachlotide(CCl4) and its mechanism.Methods The hepatic fibrosis rat model was established by CCl4composited factor.The rats in DDPs group were ig administrated with DDPs(700,350,and 175 mg/kg),the rats in positive control group with Fuzhenghuayu Capsule(1 500 mg/kg),once daily for seven weeks,and the rats in control group with distilled water.The activities of alanine transarninase(ALT),aspartate transferase(AST),and N-acetyl-β-D-glucosaminidase(NAG),and the contents of total protein(TP),albumin(ALB),and collagen type IV in serum of rats were examined;Meanwhile,superoxide dismutase(SOD) activities and the levels of malondialdehyde(MDA) and hydroxyproline(Hyp) were determined;Then,the morphological changes of liver pathology were also observed by HE and Masson stainings,and the expression of α-smooth muscle actin(α-SMA) in the liver tissue was analysed by immunohistochemical staining.Results DDPs could inhibit the increasing of ALT,AST,and NAG activities in serum of rats with hepatic fibrosis,decrease the level of collagen type IV,increase the contents of TP and ALB,lower the Hyp and MDA levels,improve the SOD activities in liver tissue,suppress the collagen fibers increasing,and reduce the expression of α-SMA as well.Conclusion DDPs have obviously protective effects on the hepatic fibrosis of rats,which may be closely related to the antiperoxidation of lipid,inhibition on the collagen fibers increasing,and reduction of the expression of α-SMA,etc.