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目的:探讨胰岛素抵抗(IR)大鼠心肌脂联素(APN)及其受体(AdipoR1和AdipoR2)表达改变和替米沙坦(TMST)的影响。方法:雄性SD大鼠50只随机选择10只作为对照组(用普通饲料喂养8周),其余40只大鼠用高果糖饮食喂养4周建立IR模型。从IR大鼠中随机选择10只作为IR组(用生理盐水灌胃4周,继续用高果糖饮食喂养);另选10只作为TMST组[用替米沙坦5 mg/(kg.d)灌胃4周,继续用高果糖饮食喂养]。所有大鼠均于喂养的第8周末,空腹采血,分别采用ELISA法和放射免疫法测定血清APN和肿瘤坏死因子-α(TNF-α)的水平。采用Western blot法测定各组大鼠心肌组织中APN、AdipoR1、AdipoR2、过氧化物酶体增殖物激活受体-γ(PPARγ)及TNF-α蛋白的表达。结果:实验第8周末,与对照组相比,IR组血清APN的水平降低(P<0.01)而血清TNF-α的水平升高(P<0.01)。大鼠心肌中APN、AdipoR1及PPAR-γ蛋白的表达降低(P<0.01);心肌中TNF-α蛋白的表达增高(P<0.01),而心肌中AdipoR2蛋白的表达无明显变化。与IR组大鼠相比,TMST组大鼠血清APN增高(P<0.05)而血清TNF-α水平降低(P<0.05),心肌APN、AdipoR1及PPAR-γ蛋白的表达增高(P<0.05);心肌中TNF-α蛋白的表达降低(P<0.05),而心肌中AdipoR2蛋白的表达无明显变化。结论:IR大鼠心肌中APN及Adi-poR1及PPARγ蛋白的表达降低;心肌中TNF-α蛋白的表达增高。TMST可通过激活PPARγ途径,增加循环中APN的水平,特别是激活心肌组织中的PPARγ,减轻炎症,提高APN及其受体的表达。
Aims: To investigate the changes of myocardial adiponectin (APN) and its receptors (AdipoR1 and AdipoR2) and telmisartan (TMST) in insulin resistance (IR) rats. Methods: Fifty male Sprague-Dawley rats were randomly selected as the control group (fed with normal diet for 8 weeks), and the remaining 40 rats were fed with high fructose diet for 4 weeks to establish IR model. Ten rabbits were randomly selected from the IR group as IR group (fed with normal saline for 4 weeks and fed with high fructose diet). Ten rabbits in the TMST group were treated with telmisartan 5 mg / (kg.d) Gavage for 4 weeks, continue to feed with high fructose diet]. All rats were fasted for fasting blood on the eighth week of feeding, and the levels of serum APN and tumor necrosis factor-α (TNF-α) were measured by ELISA and radioimmunoassay respectively. Western blot was used to detect the expression of APN, AdipoR1, AdipoR2, PPARγ and TNF-α in each group. Results: Compared with the control group, the levels of serum APN and serum TNF-α in IR group were significantly decreased at the end of the 8th week (P <0.01). The expression of APN, AdipoR1 and PPAR-γprotein in rat myocardium was decreased (P <0.01). The expression of TNF-αprotein in myocardium was increased (P <0.01), while the expression of AdipoR2protein in myocardium did not change significantly. Compared with IR group, APN, AdipoR1 and PPAR-γprotein expression in TMST group were significantly increased (P <0.05) and serum TNF-αlevel (P <0.05) ; The expression of TNF-α in myocardium decreased (P <0.05), while the expression of AdipoR2 in myocardial did not change significantly. CONCLUSION: The expression of APN, Adi-poR1 and PPARγ in myocardium of IR rats is decreased. The expression of TNF-α in myocardium is increased. TMST can increase the level of APN in circulation by activating PPARγ pathway, especially activate PPARγ in myocardial tissue, relieve inflammation and increase the expression of APN and its receptors.