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目的:探讨脂滴相关蛋白周脂素(perilipin)和脂肪分化相关蛋白(ADRP)在糖尿病发生发展过程中的变化情况以及在糖代谢异常合并非酒精性脂肪肝中的作用。方法:分别用高脂饲料喂养和高脂饲料喂养加小剂量链脲佐菌素建立糖耐量受损(IGT)和2型糖尿病大鼠模型(T2DM),采用光镜观察各组大鼠肝组织的形态学改变;用ELISA法测定血清周脂素perilipin和ADRP含量;real-time PCR技术检测肝脏组织中perilipin和ADRP mRNA的表达;用Western blotting法检测肝脏组织中ADRP蛋白的表达。结果:HE结果显示,IGT组和T2DM组大鼠均有肝细胞脂肪变性,IGT组变性更严重;各模型组的生化指标与临床相关疾病的表现一致;血清perilipin水平各组之间无差异,但IGT组和T2DM组肝组织perilipin mRNA表达明显升高(P<0.01);与IGT组相比,T2DM组perilipin mRNA表达显著增加(P<0.05)。T2DM组血清ADRP含量较其对照组明显降低(P<0.01);模型组肝组织ADRP mRNA表达明显降低(P<0.01);ADRP蛋白表达较其对照组也明显降低(P<0.01);与IGT组相比,T2DM组ADRP mRNA表达明显降低(P<0.01)。结论:血清ADRP含量在T2DM的形成中起一定的作用,与胰岛素抵抗指数呈明显负相关;高脂喂养后能导致大鼠糖代谢异常,并伴有非酒精性脂肪肝的发生;糖代谢异常合并非酒精性脂肪肝的发生可能与肝组织perilipin表达升高和ADRP表达降低有关。
Objective: To investigate the changes of perilipin and adipon differentiation-related protein (ADRP) in the development of diabetes mellitus and their roles in the abnormal glucose metabolism and non-alcoholic fatty liver. Methods: Rats with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) were respectively fed with high-fat diet and high-fat diet plus small doses of streptozotocin. The liver tissues of rats in each group were observed with light microscope The changes of perilipin and ADRP in serum were detected by ELISA. The expression of perilipin and ADRP mRNA in liver tissue was detected by real-time PCR. The expression of ADRP protein in liver tissue was detected by Western blotting. Results: Hematoxylin and eosin staining showed that hepatic steatosis was observed in both IGT group and T2DM group, and the degeneration of IGT group was more serious. The biochemical indexes of the model group were consistent with those of clinically relevant diseases. There was no difference between the two groups in serum perilipin level, However, the expression of perilipin mRNA in hepatic tissue of IGT group and T2DM group was significantly increased (P <0.01). Compared with IGT group, the expression of perilipin mRNA in T2DM group was significantly increased (P <0.05). ADRP level in T2DM group was significantly lower than that in control group (P <0.01); ADRP mRNA expression in model group was significantly lower (P <0.01); ADRP protein expression was also significantly lower than that in control group (P <0.01) ADRP mRNA expression in T2DM group was significantly lower than that in T2DM group (P <0.01). CONCLUSION: Serum ADRP content plays a role in the formation of T2DM, and has a negative correlation with insulin resistance index. High-fat diet can lead to abnormal glucose metabolism, accompanied by non-alcoholic fatty liver disease, abnormal glucose metabolism The occurrence of non-alcoholic fatty liver may be related to the increase of perilipin expression and the decrease of ADRP expression in liver tissue.