通络方剂治疗糖尿病性肝损伤的疗效及其可能机制

Therapeutic effect of Tongluo recipe on hepatic injury in streptozotocin-induced diabetic rats and its possible mechanism

目的观察通络方剂治疗糖尿病性肝损伤的疗效并探讨其可能的机制。方法雄性SD大鼠予链脲佐菌素60mg/kg腹腔注射,制备糖尿病模型。模型动物以随机数字表法分为4组(n=10):糖尿病对照(DM)组、通络方剂小剂量(TL)组、通络方剂中剂量(TM)组和通络方剂大剂量(TH)组。通络方剂剂量分别为每天0.5、1.0、2.0g/kg。同时取10只大鼠作为正常对照(CN)组。测定空腹血糖、血脂、血清肝功能指标;造模12周后处死大鼠取肝组织检测SOD、CAT、GSH-Px、MDA活性;透射电镜下观察肝组织超微结构改变。结果造模12周后糖尿病大鼠并发肝脏损伤,血清ALT、AST及AKP水平显著升高(P<0.01);透射电镜下糖尿病大鼠肝组织超微结构出现糖尿病特征性病理变化。经通络方剂治疗后,中高剂量组糖尿病鼠血清ALT、AST水平明显下降(P<0.05);糖尿病大鼠肝细胞胞质糖原颗粒减少,线粒体嵴变清晰且基质密度降低,粗面及滑面内质网形态接近正常,间质胶原纤维减少。糖尿病大鼠肝组织氧化应激水平增高,SOD和CAT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,低中高剂量组糖尿病大鼠SOD活性均显著增加、中高剂量组糖尿病大鼠MDA水平显著下降(P<0.01)。结论通络方剂对糖尿病大鼠肝损伤具有明显的治疗作用,其作用机制部分与其在一定程度上增强肝组织抗氧化酶类活性、清除脂质过氧化物有关。

Objective To investigate the therapeutic effect of Tongluo recipe（TLR） on hepatic injury in streptozotocin induced diabetic rats and the possible mechanism.Methods Experimental diabetes was induced by intraperitoneal injection of streptozotocin（60 mg/kg） in male Sprague-Dawley rats.The study included 5 groups：normal control（CN） group,diabetes mellitus control （DM） group,low-dose TLR （TL） group,middle-dose TLR （TM） group and high-dose TLR （TH） group,with 10 rats in each group.Diabetic rats in the latter three groups received 0.5 g/（kg·d）,1.0 g/（kg·d）,2.0 g/（kg·d） TLR,respectively throughout the experiment.The fasting glucose,blood lipid,and serum liver function indices were measured.Twelve weeks after treatment,rats were sacrificed and the liver tissues were collected to examine the activities of superoxide dismutase （SOD）,catalase （CAT）,glutathione peroxidase （GSH-Px）,and malondialdehyde （MDA）.The ultrastructure of liver tissues was observed through transmission electron microscope.Results The serum AST,ALT and AKP levels of diabetic rats were increased 12 weeks after intraperitoneal injection of streptozotocin （P〈0.01）,and electron microscope observation showed characteristic pathological changes of diabetes.TLR treatment （middle and high dose） obviously decreased serum AST,ALT levels（P〈0.05）and ameliorated ultrastructure changes of liver tissues：glycogen granules decreased in cytoplasm,mitochondrial cristae became distinct and electron density decreased,appearance of smooth and rough endoplasmic reticulum became nearly normal,and the interstitial collagenofiber decreased.The SOD and CAT activities were significantly decreased and MDA levels were increased in liver tissues of diabetic rats （P〈0.01）.Twelve weeks of treatment with TLR obviously improved SOD activity （at all three doses,P〈0.01） and decreased the levels of MDA （middle and high dose,P〈0.01）.Conclusion Our data suggest that TLR can improve hepatic injury in streptozotocin-induced diabetic rats,probably through increasing activities of antioxidant and depleting lipid peroxidation production.