健脾清化方通过抑制脂肪组织炎症改善肥胖的多模型验证研究

Mechanistic study of Jianpi Qinghua Formula in improving obesity by suppressing adipose tissue inflammation

关键词:  健脾清化方  肥胖  炎症

Key words:  Jianpi Qinghua Formula  obesity  inflammation

摘要:

[目的] 通过饮食诱导和遗传性肥胖模型，评估健脾清化方（JPQH）在抑制脂肪组织炎症、改善肥胖及其相关代谢紊乱中的适用性与疗效。[方法] 利用基因表达综合（GEO）数据库分析肥胖与内脏脂肪组织炎症及核因子-κB抑制蛋白激酶ε（IKKε）表达的相关性。采用饮食诱导肥胖（DIO）和瘦素受体缺陷小鼠（db/db），分为正常对照组、模型组和JPQH组。评估JPQH对小鼠的体质量、脂肪组织质量、口服葡萄糖耐量实验（OGTT）及腹腔注射胰岛素耐受实验（IPITT）的影响。通过定量聚合酶链式反应（qPCR）检测内脏脂肪组织中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）转录水平，并用免疫印记法（Western blot）检测IKKε表达。[结果] GEO数据库分析显示在体内外模型中，肥胖状态均与内脏脂肪组织炎症因子TNF-α及IKKε表达增高密切相关。在DIO小鼠中，与模型组相比，JPQH治疗后可显著降低小鼠体质量（P＜0.01）与脂肪组织质量（P＜0.001）；改善糖代谢水平，显著降低OGTT与IPITT 干预实验后的曲线下面积（AUC，P＜0.001）。qPCR与Western blot结果显示JPQH治疗后可明显抑制内脏脂肪组织中的炎症因子TNF-α、IL-6及IKKε的表达（P＜0.05或P＜0.01）。与之类似的是，在db/db小鼠中，与模型组相比，JPQH治疗后仍可降低小鼠体质量和脂肪组织质量（P＜0.05），改善OGTT干预实验后的AUC（P＜0.05），并显著降低内脏脂肪组织中的TNF-α、IL-6 mRNA水平（P＜0.01或P＜0.001），抑制IKKε表达（P＜0.05）。[结论] JPQH通过抑制脂肪组织炎症，降低肥胖小鼠体质量并改善糖代谢，显示出在饮食诱导和遗传性肥胖中的广泛适用性。

Abstract:

[Objective] To evaluate the applicability and efficacy of Jianpi Qinghua Formula（JPQH） in inhibiting adipose tissue inflammation and improving obesity and its associated metabolic disorders using diet-induced and genetic obesity models. [Methods] The gene expression omnibus（GEO） database was used to analyze the correlation between obesity，visceral adipose tissue inflammation，and the expression of inhibitor of nuclear factor kappa-B kinase ε（IKKε）. Diet-induced obesity（DIO） and leptin receptor-deficient diabetic（db/db） mice were divided into normal control，model，and JPQH groups. The effects of JPQH on body weight，adipose tissue mass，oral glucose tolerance test（OGTT），and intraperitoneal insulin tolerance test（IPITT） in mice were assessed. quantitative polymerase chain reaction（qPCR） was used to detect the transcription levels of tumor necrosis factor-alpha（TNF-α） and interleukin-6（IL-6） in visceral adipose tissue，and Western blot was employed to measure IKKε expression. [Results] Analysis of the GEO database indicates that obesity is closely associated with elevated expression of the inflammatory factor TNF-α and IKKε in visceral adipose tissue across both in vivo and in vitro models. In DIO mice，treatment with JPQH significantly reduced body weight（P＜0.01） and adipose tissue mass（P＜0.001） compared to the model group. Additionally，JPQH improved glucose metabolism，as evidenced by a significant reduction in the area under the curve（AUC） following OGTT and IPITT intervention experiments（P＜0.001）. The qPCR and Western blot results demonstrated that JPQH treatment significantly inhibited the expression of inflammatory factor TNF-α，IL-6，and IKKε in visceral adipose tissue（P＜0.01 or P＜0.05）. Similarly，in db/db mice，JPQH treatment significantly reduced body weight and adipose tissue mass compared to the model group（P＜0.05），improved AUC following the OGTT intervention（P＜0.05），markedly decreased TNF-α and IL-6 mRNA levels in visceral adipose tissue（P＜0.01 or P＜0.001），and inhibited IKKε expression（P＜0.05）. [Conclusion] JPQH reduces body weight and improves glucose metabolism in obese mice by inhibiting adipose tissue inflammation，demonstrating broad applicability in both diet-induced and genetically predisposed obesity.