利拉鲁肽1对非酒精性脂肪肝大鼠及细胞因子的影响

Effect of Liraglutide on cytokines and rats with nonalcoholic fatty liver disease

摘要:

目的探讨利拉鲁肽（Lira）对非酒精性脂肪肝（NAFLD）大鼠及细胞因子的影响。方法将雄性SD大鼠32 只随机分为3 组：正常对照组（NC）10 只、高脂组（HF）12 只、HF+Lira 组10 只。HF组、HF+Lira 组给予高脂饲料喂养16 周，HF+Lira 组高脂喂养12 周后，给予Lira 600μg/（kg·d）4 周。在16 周末处死大鼠。光学显微镜下观察肝脏病理变化；全自动生化仪检测血清三酰甘油（TG），酶联免疫法测定空腹胰岛素（FINS），并计算胰岛素抵抗指数（HOMA-IR）；GPO-PAP法测定肝脏TG 含量；酶联免疫吸附法检测血清IL-18、IL-10 水平。多组间数据比较采用单因素方差分析，组间比较采用SNK- 检验。结果与NC 组相比，HF组的肝指数、肝脏TG、血清IL-18、TG、空腹血糖（FBG）、FINS 及HOMA-IR 均升高（p <0.05）；HF+Lira 组与HF 组相比，差异有统计学意义（p <0.05），大鼠肝指数、肝脏TG、血清IL-18、TG、FBG、FINS 及HOMA-IR 均下降。HF 组血清IL-10下降（p <0.05），HF+Lira 组较HF组血清IL-10 升高（p <0.05）。相关分析显示，血清IL-18 水平与肝脂肪变、肝小叶炎症及HOMA-IR 呈正相关（p <0.05）；IL-10 水平与肝脂肪变、肝小叶炎症及HOMA-IR呈负相关（p <0.05）。结论Lira 可能通过调节NAFLD 大鼠的炎症因子平衡，减轻胰岛素抵抗和炎症反应，减少肝脏脂质沉积，从而对NAFLD起到治疗作用。

Abstract:

Objective To investigate the effect of Liraglutide on cytokines and biochemical indexes in rats with nonalcoholic fatty liver disease. Methods Thirty-two male SD rats were randomly divided into normal control group(NC, 10 rats), high fat group (HF, 12 rats), HF+Lira group (10 rats). The HF group and the HF+Lira group were given high -fat diet for 16 weeks. After 12 weeks of high -fat feeding in the HF +Lira group, Liraglutide was administered 600 μg/(kg·d) by intraperitoneal injection for 4 weeks. At the end of the 16th week, the rats were sacrificed. The pathological changes of the liver were observed under optical microscope. The serum level of total triglyceride (TG) was detected by automatic biochemical analyzer. The serum levels of interleukin-18 (IL-18), IL-10 and fasting insulin (FINS) were determined by ELISA, and insulin resistance index (HOMA-IR) was assessed by homeostasis mode assessment. TG content of the liver was measured by GPO-PAP method. The test and SNK-q test were used for statistical analyses. Results Compared with the NC group, the liver function indexes, the serum levels of IL-18 and TG, FBG, FINS and HOMA-IR in the HF group were obviously increased (p < 0.05). Compared with the HF group, the liver function indexes, the serum levels of IL-18 and TG, FBG, FINS and HOMA-IR in the HF+Lira group were all obviously lowered (p < 0.05). The serum level of IL-10 in the HF group was significantly lower than that in the NC group (p < 0.05); the level of IL-10 in the HF+Lira group was significantly higher than that in the HF group (p < 0.05). HOMA -IR, liver steatosis and hepatic lobular inflammation were positively correlated with the serum level of IL-18 (p < 0.05), but negatively correlated with the serum level of IL-10 (p <0.05). Conclusions Liraglutide can regulate the balance of inflammatory cytokines in rats with nonalcoholic fatty liver disease, alleviate insulin resistance and inflammation, reduce lipid deposition in liver, thus has therapeutic effect on nonalcoholic fatty liver disease.