吡格列酮对2型糖尿病大鼠骨骼肌脂联素受体1表达的影响

Effect of Pioglitazone on Expression of AdipoR1 in Skeletal Muscle of Type 2 Diabetic Rats

目的观察吡格列酮对2型糖尿病大鼠血清脂联素以及骨骼肌脂联素受体1(AdipoR1)表达的影响,探讨吡格列酮对2型糖尿病胰岛素抵抗的改善作用及机制。方法 40只8周龄健康雌性SD大鼠,随机分为正常对照组(n=10)、糖尿病组(n=15)及吡格列酮组(n=15)。用高糖高脂饲料加小剂量链脲佐菌素建立2型糖尿病大鼠模型,成模后吡格列酮组给予10 mg/(kg.d)吡格列酮灌胃,正常对照组和糖尿病组给予同体积生理盐水灌胃,共12周。3个月后股静脉取血,酶联免疫吸附法(ELISA)测定血清脂联素水平,留取大鼠骨骼肌,光、电镜观察骨骼肌结构,免疫组织化学染色法测定骨骼肌AdipoR1蛋白的表达。结果与正常对照组(1.73±0.32 mg/L)比较,糖尿病组血清脂联素(1.01±0.27 mg/L)水平显著降低,而吡格列酮组(1.34±0.43 mg/L)较糖尿病组显著升高,差异有统计学意义(P<0.05)。骨骼肌AdipoR1免疫组织化学染色正常对照组着色深且广泛,糖尿病组较正常对照组染色浅,吡格列酮组较糖尿病组染色深,但较正常对照组浅。光镜及电镜结果显示大鼠骨骼肌结构未见明显异常。结论 2型糖尿病大鼠血清脂联素水平及骨骼肌AdipoR1表达降低并导致糖脂代谢紊乱及胰岛素抵抗。吡格列酮可上调血清脂联素及骨骼肌AdipoR1的表达,从而调节糖脂代谢,改善胰岛素抵抗。

Aim To investigate the effects of pioglitazone on the expression of skeletal muscle AdipoR1 in type 2 diabetic rats, and explore the improvement effect and its mechanisms of pioglitazone on type 2 diabetes and insulin resistance. Methods Forty healthy eight-week-old female Spragne Dawley （SD） rats were randomly divided into normal control group（n = 10）, diabetic group（n = 15）, and pioglitazone group（n = 15 ）. Type 2 diabetes rat model was reproduced by feeding a high-sugar-fat diet followed by an intraperitoneal injection of a low dose of streptozotocin （STZ）. Rats in pioglitazone group were laraged with pioglitazone 10 mg/（ kg · d）, while those in control group and diabetic group re- ceived the same amount of normal saline for 12 weeks. After 3 months, blood was taken from femoral vein and serum adi- ponectin was measured by enzyme-linked immunosorbent assay （ELISA）. The structure of skeletal muscle was observed with light microscope and electron microscope. The protein expression of AdipoR1 in skeletal muscle was detected by im- munohistochemical staining. Results Serum adiponectin （ 1.01 ± 0. 27 mg/L） in T2DM group was significantly de- creased compared with normal control group （ 1.73 ± 0. 32 mg/L）, but that of pioglitazone group （ 1.34 ± 0.43 mg/L） was significantly increased compared with T2DM group （ P 〈 0.05 ）. Immunohistochemical staining showed that the expression of AdipoR1 in skeletal muscle was the most obvious in normal control group and was attenuated in T2DM group. The expression of AdipoR1 in skeletal muscle of piogtitazone group was more significant than that in T2DM group, but was weaker than that in normal control group. Light microscope and electron microscope showed no obvious abnormalities in skeletal muscle structure. Conclusions The levels of serum adiponectin and AdipoR1 in skeletal muscle decline in type 2 diabetic rats. Pioglitazone can up-regulate the levels of serum adiponectin and AdipoR1 in skeletal muscle thus it can downregulate the circulating levels of glucose and lipids and improve insulin sensitivity.