2型糖尿病模型大鼠胰岛β细胞损伤和益气养阴化痰祛瘀方的保护作用及机制

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为探查2型糖尿病中医证候模型大鼠(Rattus norvegicus)胰岛细胞损伤机制和中医因证治方的保护作用,采用雄性SD大鼠给予高脂高糖联合小剂量链脲佐菌素(STZ,30 mg/kg)注射的方法复制2型糖尿病气阴二虚痰瘀证模型.将成模后4周的大鼠分为模型组、西药组(盐酸吡格列酮)和中药组(益气养阴化痰祛瘀方),给药组连续灌胃干预2周,正常组和模型组均给予等量生理盐水.检测空腹血糖(FPG)、血清胰岛素(Fins)、血清胰岛素原(PI)、甘油三酯(TG)、高密度脂蛋白(HDL-c)、游离脂肪酸(FFA)、低密度脂蛋白(LDL-c),测定胰腺组织一氧化氮合酶(i NOS)、核因子(NF-?B)、超氧化物歧化酶(SOD)、血管内皮生长因子(VEGF)、肝细胞生长因子(HGF)、非受体酪氨酸激酶2(JAK-2)、蛋白激酶B(PKB)、胰淀素(amylin),观测胰脏胰岛病理及细胞面积.结果发现,模型组大鼠的FPG,血清Fins,PI,TG,FFA,LDL-c以及胰腺i NOS,NF-?B和Amylin含量升高(P<0.01或P<0.05),血清HDL-c和胰腺SOD,VEGF,HGF,JAK-2,PKB含量明显降低(P<0.01或P<0.05),胰腺的胰岛明显萎缩,结构紊乱,胰岛内可见空泡样变,细胞比积下降;益气养阴化痰祛瘀方组大鼠的FPG,血清Fins,PI,TG,LDL-c以及胰腺组织i NOS和Amylin的含量下降(P<0.01或P<0.05),胰腺SOD,VEGF,HGF,JAK-2,PKB的含量升高(P<0.01或P<0.05),胰岛结构基本正常,边界较清晰,空泡样变细胞明显减少,细胞所占面积增加.研究表明,该模型大鼠出现2型糖尿病及脂质代谢异常并伴有明显的胰岛损伤;益气养阴化痰祛瘀方在改善模型糖脂代谢的同时,有改善胰岛病理损伤及促进胰岛再生的作用,其胰岛保护性作用机制可能涉及抗氧化应激损伤、促进胰腺内皮保护性因子生成及调节JAK-2/STAT-5和PI3K/PKB信号通路. To investigate the mechanism of islet cell injury in rats with type 2 diabetes mellitus (Rattus norvegicus) and the protective effect of TCM prescriptions, male SD rats were given high fat and high glucose combined with low dose streptozotocin (STZ, 30 mg / kg) were injected into the model of type 2 diabetes mellitus and Qi Deficiency Phlegm-Stasis Syndrome.All the rats were divided into model group, western medicine group (pioglitazone hydrochloride) and Chinese medicine group The rats in the treatment group were treated with continuous gavage for 2 weeks, and the rats in the normal group and model group were given the same amount of normal saline, and the fasting blood glucose (FPG), serum insulin (Fins), serum proinsulin (PI), triglyceride TG, HDL-c, FFA and LDL-c were measured. The levels of nitric oxide synthase (iNOS), nuclear factor (NF-? B ), Superoxide dismutase (SOD), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), non-receptor tyrosine kinase 2 (JAK-2), protein kinase B (PKB) (Amylin), and the pathology and cell area of ​​pancreatic islets were observed. The results showed that FPG, Fins, PI, TG, FFA, LDL-c in serum and iNOS, NF-? B and Amylin (P <0.01 or P <0.05). The levels of serum HDL-c and pancreatic SOD, VEGF, HGF, JAK-2 and PKB were significantly decreased (P <0.01 or P < The number of FPG, serum Fins, PI, TG, LDL-c, iNOS and Amylin in pancreas decreased in Yiqi Yangyin Huatanquyu Decoction group (P <0.01 or P <0.05). The content of SOD, VEGF, HGF, JAK-2 and PKB in the pancreas increased (P <0.01 or P <0.05), the islet structure was normal and the border was clear. Significantly reduce the area occupied by cells.Studies show that the model rats with type 2 diabetes and lipid metabolism and accompanied by significant pancreatic islet injury; Yiqi Yangyin Huatanquyu decoction in improving glucose and lipid metabolism model at the same time , Which may improve the islet pathological injury and promote the islet regeneration. The mechanism of islet protective action may involve the anti-oxidative stress injury, promote the formation of protective factor of pancreas and regulate the JAK-2 / STAT-5 and PI3K / PKB signaling pathways.
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