益消方经转化生长因子β1信号通路干预糖尿病合并脂肪肝的实验研究

Intervention of Yixiao Formula in Diabetes Combined with Fatty Liver ThroughTransforming Growth Factor-β 1 Signaling Pathway

目的:探索益消方对糖尿病合并脂肪肝的影响和作用机制。方法:观察组为12周龄雄性自发糖尿病(KKAy)小鼠,按照随机数字表法随机分为模型组、中药组(益消方干预)、西药组(氯沙坦干预);对照组为同周龄雄性近交系(C57BL/6J)小鼠。干预周期为12周。观察干预前后血糖、血脂-、肝功能变化,肝脏组织进行病理染色,检测肝脏组织转化生长因子β_(1)(TGF-β_(1))信号通路蛋白和信使核糖核酸(mRNA)的变化。结果:与模型组比较,益消方干预8周体质量、肝重指数显著降低(P<0.05,P<0.01),干预第4、8、12周空腹血糖显著降低(P<0.01),干预8周胆固醇、三酰甘油、低密度脂蛋白胆固醇、谷丙转氨酶水平降低(P<0.05,P<0.01)。病理形态方面益消方干预4周脂肪变性评分下降(P<0.05)。益消方干预12周后,TGF-β_(1)及其信号蛋白、mRNA的表达均显著下调(P<0.05,P<0.01)。结论:益消方可显著改善KKAy小鼠的肥胖和糖脂代谢紊乱,调节TGF-β_(1)信号通路蛋白和基因表达,减轻肝脏脂肪变性。

Objective:To explore the effects and mechanisms of Yixiao Formula on diabetes combined with fatty liver.Methods:Twelve-week-old male spontaneous diabetic(KKAy)mice were randomly divided into a model group,a Chinese medicine(Yixiao Formula)intervention group,and a Western medicine(losartan)intervention group using a random number table.The control group consisted of age-matched male inbred(C57BL/6J)mice.The intervention period lasted 12 weeks.Changes in blood glucose,blood lipids,and liver function were observed before and after the intervention.Liver tissue was pathologically stained,and changes in proteins and mRNAs in transforming growth factor-β_(1)(TGF-β_(1))signaling pathway in liver tissues were detected.Results:Compared to the model group,the Yixiao Formula group showed a significant reduction in body weight and liver index after 8 weeks of intervention(P<0.05,P<0.01).Fasting blood glucose levels significantly decreased at 4,8,and 12 weeks of intervention(P<0.01).After 8 weeks of intervention,cholesterol,triglycerides,low-density lipoprotein cholesterol,and alanine aminotransferase levels were reduced(P<0.05,P<0.01).Pathologically,the steatosis score decreased after 4 weeks of Yixiao Formula intervention(P<0.05).After 12 weeks of intervention,the protein and mRNA expression of TGF-β_(1) was significantly downregulated(P<0.05,P<0.01).Conclusion:Yixiao Formula can significantly improve obesity and glucose-lipid metabolism disorders in KKAy mice,regulate protein and gene expression in TGF-β_(1) signaling pathway,and reduce liver steatosis.