Peroxisome proliferator-activated receptors (PPARs) are expressed on vascular tissue. To investigate the direct vasoprotective effects of PPARgamma and PPARalpha ligands, pioglitazone (3 mg/kg/day) and bezafibrate (10 mg/kg/day) were given by gavage to streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, i.p.) significantly increased NADPH oxidase, vascular call adhesion molecule-1 (VCAM-1), and osteopontin mRNA levels in the aorta, as determined by reverse transcription (RT)-polymerase chain reaction (PCR). Immunohistochemical analysis revealed that the expression of osteopontin protein was also enhanced in the streptozotocin-injected rat aorta. Pioglitazone or bezafibrate attenuated the streptozotocin-induced increase in the expression of NADPH oxidase and VCAM-1 mRNA. The enhanced expression of osteopontin gene and protein induced by streptozotocin was suppressed by pioglitazone, whereas treatment with bezafibrate had no effect on the expression of osteopontin. We also demonstrated that pioglitazone or bezafibrate prevented the streptozotocin-induced increase in angiotensin converting enzyme (ACE) gene and protein content, by the means of RT-PCR and Western blotting. On the other hand, the treatment of pioglitazone or bezafibrate in the present study did not affect glucose tolerance, serum insulin or lipid level in streptozotocin-induced diabetic rats. These results suggest that the direct anti-oxidant and anti-inflammatory effects of PPARs ligands in the aorta of streptozotocin-induced diabetic rats were not likely to have been mediated by the normalization of glucose or lipid metabolism, but instead these salutary effects appear to have been associated with the inhibition of the expression of ACE. In addition, pioglitazone appeared to be more effective on the suppression of osteopontin expression compared with bezafibrate.

译文

:过氧化物酶体增殖物激活受体(PPAR)在血管组织上表达。为了研究PPARγ和PPARα配体的直接血管保护作用,通过链饲法对链脲佐菌素诱导的糖尿病大鼠给予吡格列酮(3 mg / kg /天)和苯扎贝特(10 mg / kg /天)。通过逆转录(RT)-聚合酶链反应(PCR)确定,链脲佐菌素(65 mg / kg,腹膜内)显着增加主动脉中的NADPH氧化酶,血管调用粘附分子1(VCAM-1)和骨桥蛋白mRNA水平。免疫组织化学分析显示,在注射链脲佐菌素的大鼠主动脉中,骨桥蛋白的表达也得到了增强。吡格列酮或苯扎贝特减弱了链脲佐菌素诱导的NADPH氧化酶和VCAM-1 mRNA表达的增加。吡格列酮抑制了链脲佐菌素诱导的骨桥蛋白基因和蛋白质表达的增强,而苯扎贝特治疗对骨桥蛋白的表达没有影响。我们还证明了吡格列酮或苯扎贝特通过RT-PCR和Western印迹可以阻止链脲佐菌素诱导的血管紧张素转化酶(ACE)基因和蛋白质含量的增加。另一方面,本研究中吡格列酮或苯扎贝特的治疗并未影响链脲佐菌素诱发的糖尿病大鼠的葡萄糖耐量,血清胰岛素或血脂水平。这些结果表明,链脲佐菌素诱导的糖尿病大鼠主动脉中PPARs配体的直接抗氧化和抗炎作用不可能由葡萄糖或脂质代谢的正常化介导,但这些有益的作用似乎具有与抑制ACE表达有关。此外,吡格列酮似乎比苯扎贝特对抑制骨桥蛋白的表达更有效。

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