金钗石斛总生物碱对糖尿病合并非酒精性脂肪肝大鼠胰岛素抵抗的影响

Effects of Dendrobium nobile Lindl. alkaloids on insulin resistance in diabetic rats with non-alcoholic fatty liver disease

目的研究金钗石斛总生物碱(Dendrobium nobile Lindl.alkaloids,DNLA)对糖尿病合并非酒精性脂肪肝(NAFLD)大鼠胰岛素抵抗的影响。方法高脂高糖饲料喂养SD大鼠4周后给予腹腔注射链脲佐菌素(streptozotocin,STZ)40 mg/kg制备糖尿病合并NAFLD大鼠模型。成模大鼠随机分为模型组、DNLA 20 mg/kg组、DNLA 40 mg/kg组、DNLA 80 mg/kg组及二甲双胍100 mg/kg组,每组10只。同步设立10只SD大鼠作为空白对照。灌胃给药4周后腹主动脉取血检测大鼠空腹血糖(FPG)、空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR),H.E.染色观察肝脏及胰腺组织形态学变化,免疫组化检测胰岛中胰岛素达。结果模型大鼠FPG、FINS、HOMA-IR明显升高(P<0.05);与模型组比较,DNLA 40 mg/kg组、DNLA 80 mg/kg组FPG、FINS、HOMA-IR明显下降(P<0.05)。糖尿病大鼠肝脏组织发生脂肪变性,胰腺组织H.E.染色镜下见胰岛萎缩,岛内细胞数减少;DNLA 40 mg/kg组、DNLA 80 mg/kg组与模型组比较,肝脏脂肪变性程度减轻,胰岛内细胞数较多,免疫组化检测糖尿病合并NAFLD大鼠胰岛内胰岛素表达明显减少,与模型组比较,DNLA 40 mg/kg组、DNLA80 mg/kg组胰岛内胰岛素表达有不同程度增加。结论DNLA可降低糖尿病合并NAFLD大鼠血糖及减轻肝脏脂肪变性,机制与改善胰岛素抵抗有关。

Objective To study the effects of Dendrobium nobile Lindl.alkaloids(DNLA)on insulin resistance in diabetic rats with non-alcoholic fatty liver disease(NAFLD).Methods Sprague-Dawley(SD)rats were fed a high-fat,high-sugar diet for 4 weeks,and intraperitoneally injected with 40 mg/kg streptozotocin to establish a diabetic rat model with NAFLD.Rats were then randomly divided into the model group,DNLA 20 mg/kg group,DNLA 40 mg/kg group,DNLA 80 mg/kg group,and metformin 100 mg/kg group(n=10 rats per group).Ten normal SD rats were used as controls.Four weeks after intragastric administration of the drugs,fasting blood glucose(FPG)and fasting insulin(FINS)levels were measured,the insulin resistance index(HOMA-IR)was calculated,histological changes of the liver and pancreas were observed using hematoxylin and eosin staining,and islet insulin levels were detected by immunohistochemistry.Results FPG,FINS,and HOMA-IR were significantly increased in the model rats compared with controls(P<0.05),and FPG,FINS,and HOMA-IR were significantly decreased in the DNLA 40 mg/kg and DNLA 80 mg/kg groups compared with controls(P<0.05).Compared with the model group,the degree of fatty degeneration of the liver and the number of islet cells were reduced in diabetic rats.The expression of insulin in the islets of diabetic rats with NAFLD was significantly decreased.Compared with the model group,DNLA 40 mg/kg and DNLA 80 mg/kg groups showed a reduced extent of fatty degeneration of the liver and more islet cells.Insulin expression increased by varying degrees in the islets of the 40 mg/kg and 80 mg/kg DNLA groups.Conclusions DNLA reduces blood glucose and liver steatosis in diabetic rats with NAFLD.The mechanism may be related to the improvement of insulin resistance.