摘要
目的探讨过氧化物酶体增殖因子活化受体γ(PPARγ)在实验性2型糖尿病心肌病大鼠模型心肌结构功能损伤中的作用;柚皮苷治疗能否减轻心肌结构功能损伤及其可能的机制。方法 6周龄♂Wister大鼠80只建立实验性2型糖尿病心肌病模型,随机分为模型对照组、柚皮苷高、中、低剂量治疗组、PPARγ激动剂吡格列酮治疗组(各组16只),正常大鼠16只作为正常对照。观察不同剂量柚皮苷口服(40、20、10 mg.kg-1.d-1)治疗对心肌结构功能损伤程度的影响;免疫组化检测心肌PPARγ表达、免疫荧光定量检测外周血B型脑钠肽(BNP)和心肌肌钙蛋白I(cTnI)蛋白表达;透射电镜观察心肌细胞超微结构。结果①PPARγ在模型对照组表达增强,主要定位在血管内皮细胞及心肌细胞胞质区;相比于空白对照,模型对照组葡萄糖耐量(OGTT)阳性,心肌病损指标(心脏/体重指数、FFA、HO-MA-IR、GSP、BNP)均增高,心肌细胞超微结构损伤明显;②相比于模型对照组,中、高剂量柚皮苷和吡格列酮治疗组PPARγ表达下调,PPARγ阳性光密度呈阳性也减弱,相应灰度值增加(P<0.05);心脏/体重指数、FFA、HOMA-IR、GSP、BNP下调;OGTT及心肌细胞超微结构损伤明显改善;③相比于吡格列酮治疗组,高剂量柚皮苷治疗组在下调BNP方面明显,但改善HOMA-IR方面较差(P<0.05)。结论柚皮苷治疗减轻糖尿病心肌病心肌结构功能损伤,其机制可能与调控心肌PPARγ表达介导改善胰岛素抵抗、阻断FFA活化、抑制B型脑钠肽表达作用有关。
Aim To explore the protective effects of Naringin on myocardial structure function with STZ-induced diabetic cardiomyopathy in rats via regulation of peroxisome proliferation factor receptor γ（PPARγ）.Methods The expression of PPARγ was tested by immunohistochemical method.The expression of BNP and cardiac troponin I（cTnI） were detected by quantitative immunofluorescence.The myocardial cell ultrastructure was tested by transmission electron microscope.Results ① The enhanced PPARγ expression was prominently stained in endothelial cells and myocardial cell cytoplasm area.Compared with the normal control group,OGTT was positive.The level of heart/body weigh,FFA,HOMA-IR,GSP and BNP increased,The Myocardial cell ultrastructure was injured in diabetes cardiomyopathy model control group.② Compared with the model control group,the enhanced PPARγ expression was downregulated,PPARγ positive vascular density weakened and the corresponding gray value increasesd（P0.05）,The injury in the myocardial cell ultrastructure and OGTT ameliorated.The level of heart/body weigh,FFA,HOMA-IR,GSP and BNP decreased in a moderate or high dose of Naringin and Pioglitazone treatment groups.③ Compared with the Pioglitazone treatment group,the level of decrease was better in BNP but poorer in HOMA-IR in a high dose of Naringin treatment group.Conclusion Naringin can ease the injury in the myocardial cell ultrastructure.Its mechanisms may be associated with regulating myocardial PPARγ expression mediated improvement of insulin resistance,block activation of FFA and inhibiting BNP.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2012年第4期526-530,共5页
Chinese Pharmacological Bulletin
基金
广东省自然科学基金资助项目(No s2011010002620)
