玉米须醇提物对肝纤维化大鼠药效学研究

目的:观察玉米须(stigma maydis or com si]k)醇提取物对实验性肝纤维化大鼠的治疗效果,并探讨其作用机制.方法:用四氯化碳( CCl4)诱导大鼠肝纤维化模型(皮下注射为8周,腹腔注射为4周),将实验动物随机分为正常对照组(A)、模型组(B)、秋水仙碱组(C,0.2 mg·kg -1·d-1)、玉米须醇提取物组(D,5.4g·kg-1·d-1).除正常对照组外,其余3组均用四氯化碳(sc,每次3 mL·kg-1,2次/周)诱发肝纤维化.各组于造模第8周末处死动物,分别用放射免疫法检测血清层黏连蛋白(LN),m型前胶原( PCⅢ),透明质酸(HA)及Ⅳ型胶原(CⅣ)；RT-PCR检测肝组织Smad3 mRNA的表达；作HE染色和胶原纤维特殊染色行肝组织病理形态学观察及电镜观察治疗前后大鼠肝脏的超微结构.结果:模型组与正常组比较,大鼠血清中LN(207.6±27.4)μg·L-1,PCⅢ(280.1±3.2) μg· L-1,HA(357.0±14.1) μg·L-1,CⅣ(180.0±7.0) μg·L-1,大鼠肝组织内Smad,mRNA(0.865±0.084)水平明显升高(P＜0.01),经玉米须醇提取物治疗8周,大鼠血清中LN(162.4±2.2) μg·L-1,PCⅢ(193.2±1.8)μg·L-1,HA(219.4±3.7) μg· L-1,CⅣ( 138.0±2.5)μg·L-1水平明显降低(P＜0.01)；大鼠肝组织内Smad3 mRNA(0.410±0.026)表达明显下降(P＜0.01)；大鼠肝组织病理学检测改善显著.结论:玉米须能有效地抑制肝纤维化的发展,其机制可能是通过下调肝组织内Smad,mRNA表达,降低ECM的分泌而达到的.

Study on the Pharmacodynamic of Ethanol Extracts from Lonicera japonica in Rats with Hepatic Fibrosis

Objective:To investigate the therapeutic effects of ethanol extracts from Lonicera japonic on experimental hepatic fibrosis in rats and its mechanism.Method: The rat hepatic fibrosis model was established with carbon tetrachloride(CCl4,sc 8 weeks,ip 4 weeks).All the experimental rats were divided into four groups: normal group(A),model group(B),colchicines group(C,0.2 mg·kg-1·d-1),ethanol extracts from L.japonic group(D,5.4 g·kg-1·d-1).All groups except A were given carbon tetrachloride(sc 3 mL·kg-1,2/weeks) to induce the rat model of hepatic fibrosis.All experimental rats were killed at eight weeks after the models were established.Serum levels of hyaluronic acid(HA),laminin(LN),pro-collagen type Ⅲ peptide(PCⅢ) and collagen type Ⅳ peptide(CⅣ)were detected by radio immunoassay;and examined the Smad3 mRNA expression in rat hepatic tissue by using RT-PCR technology.The liver histopathological changes were observed with HE or special collegin fibrosis staining and its ultrasructures were observed in electronic-microscope before and after therapy.Result: Compared with normal group in model group,the serum level of LN(207.6±27.4) μg·L-1,PCⅢ(280.1±3.2) μg·L-1,HA(357.0±14.1) μg·L-1),CⅣ(180.0±7.0) μg·L-1,the Smad3 mRNA expression in the rat hepatic tissue were significantly increased(P<0.01),ethanol extracts of L.japonica treatments(8 weeks) significantly decreased the serum level of LN(207.6±27.4) μg·L-1,PCⅢ(280.1±3.2)μg·L-1,HA(357.0±14.1)μg·L-1,CⅣ(180.0±7.0) μg·L-1(P<0.01).Also the Smad3 mRNA expression in the rat hepatic tissue decreased markedly(P<0.01).The liver histopathological improvement was also obvious.Conclusion: L.japonica can effectively suppress the development of hepatic fibrosis,its mechanism may be achieved by down-regulating the Smad3 mRNA expression in hepatic tissue,and reducing the secretion of extracellular matrix(ECM).