论文部分内容阅读
目的:探讨赖氨大黄酸(RHL)对链脲佐菌素(STZ)诱导的KK/HlJ糖尿病(DM)小鼠胰岛素抵抗的改善作用,并阐明其作用机制。方法:腹腔注射STZ(50mg·kg~(-1))并给予DM专属饲料制备KK/HlJ小鼠DM模型。将48只小鼠分为正常对照组、模型组、低剂量RHL治疗组(25mg·kg~(-1))和高剂量RHL治疗组(50mg·kg~(-1)),每组12只,共治疗16周。采用葡萄糖氧化酶法检测各组小鼠空腹血糖(FBG)、总胆固醇(TC)和甘油三酯(TG)水平,HE染色观察小鼠胰腺组织形态表现,免疫组织化学法检测小鼠胰岛组织中胰岛素水平,酶联免疫吸附法(ELISA)检测小鼠血清胰岛素、C反应蛋白(CRP)和肝脏组织中肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)水平,Western blotting法检测小鼠肝脏组织中糖原合成相关基因(PI3K、AKT和GSK-3β)的磷酸化表达水平。结果:与模型组比较,低和高剂量RHL治疗组小鼠FBG、TG和TC水平降低(P<0.05),胰岛素水平无明显变化(P>0.05)。与模型组比较,低和高剂量RHL治疗组小鼠血清CRP水平和肝脏组织中TNF-α和IL-6水平降低(P<0.01)。HE染色,与模型组比较,低和高剂量RHL治疗组小鼠胰岛形态有一定恢复,偶见炎症浸润;免疫组织化学染色,与模型组比较,低剂量RHL治疗组小鼠棕色颗粒状物质明显减少,而高剂量RHL治疗组小鼠胰岛中未见棕色颗粒状物质。与模型组比较,低和高剂量RHL治疗组小鼠糖原合成相关基因PI3K、AKT和GST-3β磷酸化表达水平升高(P<0.01)。结论:RHL对STZ所致KK/HlJ DM小鼠胰岛素抵抗有改善作用,其机制可能与RHL促进糖原合成有关。
Objective: To investigate the effect of lysine on the insulin resistance in streptozotocin (STZ) -induced KK / HlJ diabetic mice and to elucidate its mechanism of action. Methods: The model of KK / HlJ mice was established by intraperitoneal injection of STZ (50 mg · kg -1) and DM alone. 48 mice were divided into normal control group, model group, low dose RHL treatment group (25mg · kg -1) and high dose RHL treatment group (50mg · kg -1), 12 in each group For a total of 16 weeks. The levels of fasting blood glucose (FBG), total cholesterol (TC) and triglyceride (TG) in each group were detected by glucose oxidase method. The morphological changes of pancreas were observed by HE staining. The serum levels of insulin, C-reactive protein (CRP) and liver tissue were measured by ELISA and the level of TNF-α and IL-6 were detected by Western blotting Method to detect the phosphorylation of glycogen synthesis-related genes (PI3K, AKT and GSK-3β) in mouse liver tissue. Results: Compared with the model group, the levels of FBG, TG and TC in the low and high dose RHL treatment groups were decreased (P <0.05), while the insulin level did not change significantly (P> 0.05). Compared with the model group, the levels of serum CRP and the level of TNF-α and IL-6 in the liver of low and high dose RHL treatment groups decreased (P <0.01). Compared with the model group, the morphological changes of islets in the low and high dose RHL treatment groups were recovered, and inflammatory infiltration was seen occasionally. Immunohistochemical staining showed that the brown granular substance in the low dose RHL treatment group was significantly higher than that in the model group Decreased, while the high dose of RHL treatment group mice pancreatic islet no brown granular material. Compared with the model group, the phosphorylation of glycogen synthesis-related genes PI3K, AKT and GST-3β in low and high dose RHL treatment groups increased (P <0.01). Conclusion: RHL can improve the insulin resistance of KK / HlJ DM mice induced by STZ. The mechanism may be related to the promotion of glycogen synthesis by RHL.