基于IKKε在代谢中的作用探讨健脾清化方对饮食介导肥胖小鼠体脂影响及其机制

Effects and mechanism of Jianpi Qinghua Recipe on body fat of diet induced obesity mice based on the role of IKKε in metabolism

目的探讨健脾清化方对肥胖模型(DIO)小鼠体质量的影响及其机制。方法以高脂饲料喂养C57/BL小鼠构建肥胖模型,造模成功后按体质量随机分为模型组(HFD组)、健脾清化方组(JPQH组),另设立正常饲料喂养的C57/BL小鼠为正常对照组(NOR组)。JPQH组按等效剂量15 g·kg^(-1)·d^(-1)灌胃给药,HFD组和NOR组以等量的0.9%Na Cl溶液灌胃干预6周。通过体质量、体脂、肝脏病理等指标评估各组代谢表型的差异;并采用Western blotting法及RT-PCR法检测脂肪组织内IkB激酶ε(IKKε)、解耦联蛋白1(UCP-1)蛋白及基因的表达。结果与NOR组比较,HFD组小鼠体质量、体内脂肪含量显著增高(P<0.05),而健脾清化方能显著改善高脂喂养引起的体质量、体内脂肪增高(P<0.05)。病理观察发现,健脾清化方能显著改善高脂喂养引起的肝脏脂肪异位沉积。与NOR组比较,HFD组脂肪组织内IKKε的蛋白及基因表达明显上调(P<0.05),UCP-1的蛋白及基因表达明显下调(P<0.05);与HFD组比较,JPQH组脂肪组织内IKKε蛋白及基因表达水平降低(P<0.05),而UCP-1的蛋白及基因表达水平提高(P<0.05)。结论健脾清化方能降低肥胖小鼠体内脂肪含量,从而显著改善高脂饲养引起的小鼠体质量增加及脂肪异位沉积,其机制可能与调节IKKε/UCP-1通路,提高机体能量消耗有关。

Objective To study the effects and mechanism of Jianpi Qinghua Recipe on body weight of diet induced obesity （ DIO ） mice. Methods DIO model was established in C57/BL by high fat feeding. After successful modeling, the mice were randomly divided into the model group and Jianpi Qinghua Recipe （JPQH） group according the body weight. C57/BL mice fed with normal diet were taken as the normal control group. The JPQH group was treated with Jianpi Qinghua Recipe at daily dose of 15 g crude drug/kg （equivalent dose in mice） for intragastric administration, the model group and normal control group were treated with equivalent 0.9% NaC1 solution,with a course of 6 weeks. The differences on the metabolic phenotypes in each group were evaluated by body weight,body fat and liver pathology. The protein and gene expressions of IKB kinase e （IKKe） and uncoupling protein- 1 （ UCP- 1 ） in adipose tissue were detected by Western blotting and RT-PCR. Results Compared with the normal control group, the body weight and body fat content were increased significantly in the model group （ P 〈 0.05 ）, while Jianpi Qinghua Recipe could significantly improve the increase of body weight and fat caused by high fat feeding（ P 〈 0.05 ）. Pathological observation showed that Jianpi Qinghua Recipe could significantly improve the liver fat ectopic deposition induced by high fat diet. Compared with the normal control group, the protein and gene expressions of IKKe in adipose tissue were significantly up-regulated in the model group （ P 〈 0.05 ）, while the protein and gene expressions of UCP-1 were significantly down-regulated （P 〈 0.05 ）. Compared with the model group, the protein and gene expressions of IKKe in adipose tissue were decreased in JPQH group （ P 〈 0.05 ）, and the protein and gene expressions of UCP- 1 were increased （ P 〈 0.05 ）. Conclusion Jianpi Qinghua Recipe can decrease the body fat content in obese mice, and significantly improve the increase of body weight and liver fat ectopic deposition caused by high fat feeding. Its mechanism may be associated with regulating IKKe / UCP-1 pathway and improving the body energy consumption.