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作 者:李焱[1] 黄滨[1] 程桦[1] 梁真[1] 刘珊英[1]
机构地区:[1]中山大学附属第二医院内分泌科,广州510120
出 处:《中国医学科学院学报》2006年第6期761-765,共5页Acta Academiae Medicinae Sinicae
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。0.bjective To explore the effect of peroxiseme proliferator-αctivated receptor-α ( PPAR-α) agonist fenofibrate on adipokines expression in high-fat diet fed SD rats and its relationship to insulin resistance (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 il 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 adiponeetin 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, ATIR, and IL-6 had no significant difference among these three groups (P 〉 0.05 ). Conclusion PPAR-ct agonist fenofibrate may reverse high-fat diet induced lipid abnormalities, improve insulin sensi- tivity, and regulate the mRNA expressions of TNF-α and adiponectin in adipose tissues.
关 键 词:过氧化物酶体增殖物激活受体-Α 激动剂 脂肪因子 游离脂肪酸 胰岛素抵抗
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