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目的探讨利拉鲁肽(liraglutide)对非酒精性脂肪肝大鼠及chemerin的影响。方法将雄性SD大鼠随机分为对照组、模型组、干预组,每组10只。模型组和干预组给予高脂饲料喂养16周,干预组高脂喂养12周后,给予liraglutide600μg/(kg·d)腹腔注射4周。16周末检测血清ALT、AST、TNF-α、IL-6、chemerin及胰岛素(FINS)水平,并计算胰岛素抵抗指数(HOMA-IR);测定肝匀浆SOD、MDA含量;光学显微镜观察肝脏病理变化;RT-q PCR法测定肝组织chemerin mRNA表达水平。结果与对照组相比,模型组血清ALT、AST、TNF-α、IL-6、FINS、HOMA-IR及肝匀浆MDA水平均明显升高(P<0.05),肝匀浆SOD明显降低(P<0.05);干预组与模型组相比,血清ALT、AST、TNF-α、IL-6、FINS、HOMA-IR及肝匀浆MDA水平均明显降低(P<0.05),肝匀浆SOD升高(P<0.05);模型组血清chemerin及肝脏chemerin mRNA表达水平较对照组显著增强(P<0.05);干预组较模型组血清chemerin及肝脏chemerin mRNA表达显著下降(P<0.05)。相关分析显示血清chemerin与TNF-α的表达水平呈正相关(r=0.83,P<0.05)。结论Liraglutide可能通过调节NAFLD大鼠的chemerin水平,减轻胰岛素抵抗、炎症反应和氧化应激,减少肝脏脂质沉积,从而对NAFLD起到治疗作用。
Objective To investigate the effect of liraglutide on non-alcoholic fatty liver in rats and chemerin. Methods Male SD rats were randomly divided into control group, model group and intervention group, with 10 rats in each group. The model group and the intervention group were fed with high-fat diet for 16 weeks, and the intervention group were fed with high-fat diet for 12 weeks. Then, liraglutide 600μg / (kg · d) was injected intraperitoneally for 4 weeks. The levels of serum ALT, AST, TNF-α, IL-6, chemerin and FINS were detected at the 16th weekend, and the insulin resistance index (HOMA-IR) was calculated. The content of SOD and MDA in the liver homogenate were measured. The mRNA expression of chemerin in liver tissue was detected by RT-q PCR. Results Compared with the control group, the levels of serum ALT, AST, TNF-α, IL-6, FINS, HOMA-IR and liver homogenate MDA in model group were significantly increased (P < P <0.05). Compared with the model group, serum ALT, AST, TNF-α, IL-6, FINS, HOMA-IR and liver homogenate MDA in the intervention group were significantly decreased (P <0.05). The levels of chemerin and chemerin mRNA in the model group were significantly higher than those in the control group (P <0.05). The levels of chemerin and chemerin mRNA in the intervention group were significantly lower than those in the model group (P <0.05). Correlation analysis showed that there was a positive correlation between serum chemerin and TNF-α (r = 0.83, P <0.05). Conclusion Liraglutide may have a therapeutic effect on NAFLD by regulating the chemerin level in NAFLD rats, reducing insulin resistance, inflammatory reaction and oxidative stress, reducing hepatic lipid deposition.