【摘要】 目的探讨过氧化物酶体增殖物激活受体-α(PPAR-α)激动剂非诺贝特对高脂饮食诱导的肥胖SD大鼠胰岛素敏感性和部分脂肪因子表达的影响。方法随机将大鼠分为3组(n=10):高脂饮食喂养加非诺贝特治疗组(简称治疗组)、高脂饮食喂养组(简称高脂组)和标准饮食对照组(简称对照组)。高脂饮食喂养SD大鼠6周后,以非诺贝特20mg·kg-1·d-1灌胃治疗4周,以RT-PCR法半定量测定脂肪组织部分脂肪因子肿瘤坏死因子-a(TNF-α)、白细胞介素-6(IL-6)、血管紧张素原(AGT)、血管紧张素Ⅱ1型受体(AT1R)及脂联素mRNA的表达,同时检测血游离脂肪酸(FFA)、甘油三脂(TG),并用稳态模式评估法(HOMA)评价胰岛素抵抗(IR)指数。结果非诺贝特治疗4周后,高脂组、治疗组、对照组的血FFA分别为(2·37±0·60)、(1·59±0·30)、(1·33±0·34)mmol/L,TG分别为(0·48±0·11)、(0·30±0·04)、(0·36±0·07)mmol/L,HOME-IR指数分别为12·30±3·97、5·03±1·88、4·17±1·27;脂肪组织TNF-α的mRNA半定量值分别为1·726±1·408、0·713±0·711、0·593±0·382,脂联素分别为0·660±0·192、0·949±0·35、0·936±0·130;上述各指标治疗组与高脂组比较差异均有显著性(P<0·05),治疗组与对照组比较差异均无显著性(P>0·05);3组间的AGT、AT1R和IL-6的mRNA表达差异均无显著性(P>0·05)。结论PPAR-α激动剂非诺贝特具有改善高脂饮食诱导的脂质异常、提高胰岛素敏感性以及调节脂肪因子表达的作用。更多还原

【Abstract】 Objective To explore the effect of peroxisome proliferator-activated receptor-α (PPAR-α) agonist fenofibrate on adipokines expression in high-fat diet fed SD rats and its relationship to insulin resis- tance (IR). Methods Rats were randomized into three groups (n=10):HD group,fed with high-fat diet;HDF group,fed with high fat diet and treated with fenofibrate;and control group,fed with normal diet. Animals were sacrificed after 4-week follow-up. Plasma lipids,fasting plasma insulin,free fatty acids (FFA),and insulin sensitivity were detected. Reverse transcription-polymerase chain reaction was used to semi-quantitatively determine the mRNA expression of adipokines including tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),angiotensinogen (AGT),angiotensin Ⅱ type 1 receptor (AT1R),and adiponectin in brown fat. Results The plasma level of FFA,TG,and homeostatic model approach-IR index were(2.37±0.60)vs (1.59±0.30)vs(1.33±0.34 )mmol/L,(0.48±0.11)vs(0.30±0.04)vs(0.36±0.07)mmol/L,and 12.30±3.97 vs 5.03±1.88 vs 4.17±1.27 in the HD group,HDF group,and control group after 4 weeks of treatment with fenofibrate,respectively. The mRNA expressions of TNF-α and adiponectin were 1.726±1.408 vs 0.713±0.711 vs 0.593±0.382 and 0.660±0.192 vs 0.949±0.35 vs 0.936±0.130 in these three groups, which showed significant difference between HD group and HDF group(P<0.05),while no significant difference between HDF group and control group (P>0.05). The mRNA expressions of AGT,AT1R,and IL-6 had no significant difference among these three groups(P>0.05). Conclusion PPAR-α agonist fenofibrate may reverse high-fat diet induced lipid abnormalities,improve insulin sensitivity,and regulate the mRNA expressions of TNF-α and adiponectin in adipose tissues.更多还原