桑白皮黄酮提取物对2型糖尿病大鼠非酒精性脂肪肝血管生成相关基因的影响

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目的:初步探索桑白皮黄酮提取物对2型糖尿病大鼠非酒精性脂肪肝的治疗作用及机制研究。方法:将24只雄性大鼠随机分为3组,分别为正常组、模型组、桑白皮黄酮组(1.0 g·kg~(-1))。采用腹腔注射小剂量链脲佐菌素(streptozocin,STZ)结合高脂饲料喂养的方法,建立2型糖尿病伴非酒精性脂肪肝的模型,灌胃治疗16周时,观察比较桑白皮黄酮提取物对各组大鼠血清中空腹血糖(FBG),总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C),糖耐量(OGTT)变化,油红O染色和苏木素-伊红(HE)染色观察肝脏病理改变,实时荧光定量聚合酶链式反应(Real-time PCR)检测肝脏血管内皮生长因子(vascular endothelial growth factor,VEGF),血小板衍生因子(platelet derived growth factor,PDGF)mRNA的表达。结果:灌胃干预16周后,与正常组比较,模型组大鼠FBG,TC,TG,LDL-C,含量均显著高于正常组(P<0.05),应用桑白皮黄酮治疗后,上述生化指标较模型组均有显著下降(P<0.05)。糖耐量试验显示模型组胰岛素敏感性下降,应用桑白皮黄酮治疗后胰岛素敏感性较模型组有显著改善。油红O染色结果显示模型组肝细胞胞浆内可见大量红染的脂肪滴,而桑白皮黄酮组肝细胞胞浆内未见红染的脂肪滴。HE染色结果显示模型组肝小叶中肝细胞发生明显的小泡样脂肪变性,部分肝细胞中脂滴融合成大的脂肪空泡,小叶中可见点状坏死,周围有炎性细胞浸润,而桑白皮黄酮组肝细胞结构正常。模型组肝脏中VEGF,PDGF mRNA表达量较正常组有显著升高,应用桑白皮黄酮治疗后,肝脏中VEGF,PDGF mRNA表达量明显降低(P<0.05)。结论:桑白皮黄酮提取物对实验性2型糖尿病大鼠非酒精性脂肪性肝有一定的防治作用,其作用机制可能与抑制肝脏中VEGF,PDGF mRNA的表达有关。 Objective: To explore the therapeutic effect and mechanism of flavonoid extract of Morus alba on nonalcoholic fatty liver in type 2 diabetic rats. Methods: 24 male rats were randomly divided into 3 groups: normal group, model group and Morus alba group (1.0 g · kg -1). The model of type 2 diabetes mellitus with non-alcoholic fatty liver was established by intraperitoneal injection of low dose streptozocin (STZ) combined with high fat diet. After 16 weeks of intragastric administration, the extraction of flavonoids from Morus alba The changes of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), glucose tolerance (OGTT) Hematoxylin and eosin (HE) staining was used to observe the pathological changes of the liver, and real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the expression of vascular endothelial growth factor (VEGF), platelet derived growth factor , PDGF) mRNA expression. Results: Compared with the normal group, the content of FBG, TC, TG, LDL-C in the model group was significantly higher than that in the normal group after 16 weeks of intragastric administration (P <0.05) Biochemical indicators than the model group were significantly decreased (P <0.05). Glucose tolerance test showed that the insulin sensitivity of the model group decreased, the application of saponins after treatment of insulin sensitivity than the model group significantly improved. Oil red O staining results showed that a large number of red-stained fat droplets were observed in the cytoplasm of liver cells of the model group, while no red-stained fat droplets were observed in the cytoplasm of liver cells of the Sang white skin flavone group. Hematoxylin-eosin staining showed that hepatocytes in the model group showed obvious vesicle-like steatosis. Some lipid droplets in some hepatocytes fused into large fat vacuoles, and some necrotic cells appeared in the lobules with infiltration of inflammatory cells. The structure of liver cells in the white-flavone group was normal. The expression of VEGF and PDGF mRNA in the liver of the model group was significantly higher than that of the normal group. The expression of VEGF and PDGF mRNA in the liver decreased significantly (P <0.05). CONCLUSION: Fructus Mori flavonoids extract can prevent and treat nonalcoholic fatty liver in experimental type 2 diabetic rats. Its mechanism may be related to the inhibition of the expression of VEGF and PDGF mRNA in the liver.
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