姜黄素衍生物L6H4对糖脂代谢异常大鼠的治疗作用及其机制

The therapeutic effect of curcumin derivatives L6H4 on rats with abnormalities of glucose and lipid metabolism and its mechanism

目的:观察姜黄素衍生物L6H4对糖脂代谢异常大鼠代谢指标的影响,并对其作用机制进行初步探讨。方法:24只8周龄雄性SD大鼠随机分为正常空白对照组(NC组,n=8),高脂组(HF组,n=8)和高脂治疗组(FT组,n=8),后2组高糖高脂饲料喂养12周。第5周时开始给予药物治疗8周,12周末检测各组大鼠血清生化指标、肝脏和骨骼肌的甘油三酯(TG),以及与糖脂代谢相关的多项指标,并观察光镜下肝脏与骨骼肌的病理学变化。结果:1HF组与NC组比较,体质量增加(P<0.05),肝湿质量、空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOME-IR)、血清TG、肝脏TG、骨骼肌TG、血清ALT、血清游离脂肪酸(FFA)、高敏C反应蛋白(hs-CRP)和白介素6(IL-6)水平均升高(均P<0.01),脂联素(ADP)、瘦素(LEP)下降(分别P<0.01,P<0.05),成纤维细胞生长因子21(FGF-21)差异无统计学意义(P>0.05);2FT组与HF组比较,FINS、肝湿质量与肝指数差异均无统计学意义(P>0.05),体质量、肝脏TG、血TG、ALT、FBG、HOMEIR、FFA、hs-CRP水平降低(P<0.01),骨骼肌TG、IL-6水平下降(P<0.05),FGF-21、ADP升高(P<0.01);3HF组肝脏可见明显脂肪变及炎症细胞浸润,骨骼肌细胞间质可见脂肪浸润,治疗后肝脏脂肪变以及骨骼肌脂肪浸润明显改善。结论:姜黄素衍生物L6H4对高脂高糖喂养大鼠具有控制体质量、保护肝功能、改善胰岛素抵抗的作用,可能与其调脂、抑制炎症、降低异位脂肪存积相关。

Objective： To observe the effect of curcumin derivatives L6H4 on rats with abnormalities of glucose and lipid metabolism, and preliminarily study the mechanism of it. Methods： Twenty-four male SD rats were randomly allocated into three groups： normal control group（NC group, n=8）, high fatty group（HF group, n=8）, and fatty treatment group（FT group, n=8）. To fed the rats in HF group and FT group with high fat and surgar diet for 12 weeks, from the 5th week with drug treatment for 8 weeks, at the end of 12 th week, the following indexes were measured respectively in each group： serum biochemical indexes, liver and skeletal muscle triglycerides, and related indicators of sugar and lipid matabolism. Observing the liver pathological changes at the same time. Results： 1Compared HF group with NC group： weight gain（P〈0.05）, liver weight, fasting blood glucose（FBG）, fasting insulin（FINS）, insulin resistance index（HOME-IR）, serum triglycerides, liver triglyceride, skeletal muscle triglycerides, serum ALT, FFA, high-sensitivity c-reactive protein（hs-CRP） and interleukin 6 increased（P〈0.01）, adiponectin and leptin decreased（P〈0.01, P〈0.05, respectively）. 2Compared the FT group with HF group： weight and ALT loss（P〈0.01）, liver weight and liver index had no obvious difference, FBG decreased（P〈0.01）, FINS（P〈0.05）, the HOME-IR decreased（P〈0.01）, serum triglycerides, liver triglycerides and skeletal muscle triglyceride were reduced（P〈0.01, P〈0.01, and P〈0.05, respectively）, FFA and hs-CRP reduced（P〈0.01）, fibroblast growth factor 21（FGF-21） increased（P〈0.01）, adiponectin, interleukin 6 increased with P〈0.01 and P〈0.05, respectively. 3Inflammatory injury in hepatic tissue of HF groups was slight, while fatty degeneration in hepatic tissue and skeletal muscle were obvious, the condition was significantly reduced in the FT group. Conclusion： Curcumin derivatives L6H4 has the effect of controlling weight, protecting the liver function and improving the condition of insulin resistance on high fat and sugar-fed rats.