通络方剂对糖尿病大鼠肝纤维化相关血清学指标及形态学的影响

Effects of Tongluo recipe on serum hepatic fibrosis markers and hepatic morphological changes in diabetic rats

目的探讨通络方剂(Tongluo recipe,TLR)对糖尿病大鼠肝纤维化相关血清学指标及形态学的影响。方法 SD大鼠予链脲佐菌素(streptozotocin,STZ)60mg/kg腹腔注射,制备糖尿病模型。模型动物按随机数字表法分为2组,每组10只:糖尿病对照组、通络方剂干预组[TLR溶于生理盐水,剂量为2.0g/(kg·d)],同时取10只大鼠作为正常对照组,正常对照组和糖尿病对照组大鼠仅给予等量的生理盐水溶液,每日同一时间灌胃。造模12周后测血清肝纤维化指标,取肝组织测超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA),观察肝组织形态学改变。结果糖尿病大鼠血清透明质酸(hyaluronic acid,HA)、Ⅳ型胶原(collagentypeⅣ,Ⅳ-c)水平显著升高(P<0.01),肝血窦边缘及肝汇管区胶原纤维增生,Disse间隙贮脂细胞增生;糖尿病大鼠肝组织SOD活性显著降低,MDA水平显著升高(P<0.01)。经通络方剂治疗12周后,血清HA、Ⅳ-c水平显著降低(P<0.05),肝纤维化病理形态有明显改善;糖尿病大鼠肝组织SOD活性显著增加、MDA水平显著下降(P<0.01),氧化应激水平有所下降。结论通络方剂可降低糖尿病大鼠血清肝纤维化指标,改善肝纤维化的病理形态,其作用机制可能与其增强了肝组织抗氧化酶类活性以及清除脂质过氧化物有关。

Objective To investigate the effects of Tongluo recipe （TLR）,a compound ripe of traditional Chinese drugs,on serum hepatic fibrosis markers and hepatic morphological changes of diabetic rats. Methods Experimental diabetes was induced by intraperitoneal injection of streptozotocin （60 mg/kg） in male Sprague-Dawley rats. The rats were divided into normal control （CN）,diabetes mellitus control （DM）,and TLR treatment group [TRL,2.0 g/（kg·d）,once a day,intragastrical gavage],10 rats in each group. After 12 weeks of treatment,serum hepatic fibrosis markers hyaluronic acid （HA）,collagen type Ⅳ （Ⅳ-c）,laminin （LN）,procollagen type Ⅲ （PC Ⅲ）,and superoxide dismutase （SOD） and malondialdehyde （MDA） in liver tissues were measured. The morphological changes of liver tissues were observed with light microscopy and transmission electronic microscopy. Results The serum HA and Ⅳ-c levels of diabetic rats were increased （P0.01） compared with CN group. Light microscopy and transmission electron microscopy displayed that there were collagen fibers hyperplasia in hepatic sinusoid and portal area,and fat-storing cells hyperplasia in Disse space. SOD activities were decreased and the MDA levels were increased in liver tissues of diabetic rats than in those of CN rats （P0.01）. After 12 weeks＇ TLR treatment,the serum HA and Ⅳ-c levels were decreased than those in DM group （P0.05） and morphological changes were ameliorated. TLR treatment obviously improved SOD activity and decreased the levels of MDA （P0.01）. Conclusion Tongluo recipe decreases the levels of serum hepatic fibrosis markers and ameliorates morphological changes of hepatic fibrosis in diabetic rats,which probably through increasing activities of antioxidatant and depleting lipid peroxidation products.