小檗碱对2型糖尿病大鼠骨骼肌糖脂代谢的影响及其机制

摘要

Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor(PPARs) ɑ/γ/δ protein expression.Methods Type 2 diabetes mellitus rats were induced by an injection of 35 mg·kg-1 streptozotocin(STZ)and a high-carbohydrate/high-fat diet for 16 weeks.From week 17 to 32,diabetic rats were given low-,middle-,high-dose berberine(75,150,300 mg·kg-1),fenofibrate(100 mg·kg-1) and rosiglitazone(4 mg·kg-1) by oral administration,respectively.The skeletal muscle structure was observed with hematoxylin-eosin (HE) staining,glycogen and triglyceride contents were measured by spectrophotometry and PPAR ɑ/γ/δ protein expressions were detected bv immanohistochemistry.Results Fiber distribution remained normal in skeletal muscles of all the groups,middle-,high-dose berberine partly improved diabetic fibre atrophy,increased glycogen and decreasedtriglyceride levels in diabetic musele(P＜0.01).Middle-,high-dose berberine and rosiglitazone all significantly reduced PPARγprotein level in diabetic skeletal muscle (P＜0.01):middle-,high-dose berberine and fenofibrate strikingly increased both PPARɑ and PPAR6 expression(P＜0.01).Conclusion Berberine modulates PPAR ɑ/γ/δ protein expression in diabetic skeletal muscle which may contribute to ameliorate fibre damage and glucolipid metabolization.%目的 观察小檗碱对糖尿病大鼠骨骼肌病理结构改变和糖脂代谢紊乱的影响及其与PPAR ɑ/γ/δ蛋白表达的关系.方法 注射链脲菌素(35 mg·kg-1,i.p.)加高糖高脂饲料喂养16周建立2型糖尿病大鼠模型,随后16周每天分别拌食给予低中高剂量小檗碱(75、150、300 mg·kg-1)、非诺贝特(100 mg·kg-1)和罗格列酮(4 mg·kg-1),用HE染色检查骨骼肌结构病变、分光光度法测定肌糖元和甘油三脂含量及免疫组化检测PPAR ɑ/γ/δ的表达.结果 骨骼肌纤维在各组大鼠中仍正常分布,中高剂量小檗碱部分地改善糖尿病肌纤维的萎缩,增加肌糖元和降低甘油三脂含量(P＜0.01).中高剂量小檗碱和罗格列酮都能明显降低糖尿病大鼠骨骼肌中PPAR7蛋白水平(P＜0.01),中高剂量小檗碱和非诺贝特能促进PPARɑ和PPARδ的表达(P＜0.01).结论 小檗碱调控骨骼肌PPAR ɑ/γ/δ蛋白的表达可能是其改善糖尿病骨骼肌纤维萎缩和糖脂代谢紊乱的机制之一.