摘要
目的 明确地黄宝源颗粒对糖尿病阴虚热盛证大鼠的药效作用并基于尿代谢组学探讨其作用机制.方法 采用高糖高脂饲料饲喂结合链脲佐菌素(streptozocin,STZ)造成2型糖尿病大鼠模型,在此基础上,灌胃附子干姜水提液构建糖尿病阴虚热盛证大鼠模型.连续4周灌胃给予地黄宝源颗粒.检测大鼠空腹血糖、糖化血红蛋白、糖耐量及腺组织病理变化等糖尿病药效作用指标,饮水量、摄食量、血清血栓素B2(TXB2)含量等阴虚热盛证候指标,明确地黄宝源颗粒对糖尿病阴虚热盛证大鼠的药效作用,并结合尿代谢组学分析探讨地黄宝源颗粒对糖尿病阴虚热盛证大鼠的作用机制.结果 在药效方面,地黄宝源颗粒能降低大鼠血糖、血清TXB2含量、饮水量、摄食量、糖化血红蛋白含量、糖耐量并改善其胰腺组织病理形态;在机制方面,尿代谢组学提示,与正常组比较,T2DM阴虚热盛组共筛选出936个差异代谢物,地黄宝源颗粒显著回调了其中69个(下调53个,上调16个),地黄宝源颗粒可有效调节糖尿病阴虚热盛证大鼠甘油磷脂代谢、胆汁分泌、类固醇降解、初级胆汁酸生物合成等代谢通路,发挥抗糖尿病阴虚热盛证的作用.结论 地黄宝源颗粒能有效改善大鼠糖尿病阴虚热盛证,并调节糖尿病阴虚热盛证大鼠甘油磷脂代谢、胆汁分泌、类固醇降解、初级胆汁酸生物合成等代谢通路.
Abstract
Objective To clarify the pharmacodynamic effect of Dihuang Baoyuan Granules (DHBY) on diabetic rats with Yin deficiency and heat excess,and to explore its mechanism of action based on urinary metabolomics. Methods based on the insulin-resistant type 2 diabetic rat model fed with high sugar and high-fat diet combined with intraperitoneal injection of STZ,the aqueous extract of dried aconite and ginger was intragastric to construct the diabetic rat model of Yin deficiency and heat excess. DHBY was administered by gavage for 4 consecutive weeks. The pharmacodynamic effect indicators of diabetes such as fasting blood glucose,glycated hemoglobin,glucose tolerance,and pathological changes of glandular tissue in rats were detected,and the indicators of Yin deficiency and heat excess syndrome such as water intake,food intake,and serum thromboxane B2 (TXB2) content were used to clarify the pharmacodynamic effect of DHBY on Yin deficiency and heat excess diabetic rats,and the mechanism of action of Huang Baoyuan granules on Yin deficiency and heat excess diabetic rats was explored by urinary metabolomics analysis. Results In terms of efficacy,DHBY can reduce blood glucose,serum TXB2 content,water intake,food intake,glycated hemoglobin content,and glucose tolerance and improve the pathological morphology of pancreatic tissue in rats. In terms of mechanism,urinary metabolomics suggested that compared with the normal group,936 differential metabolites were screened out in the T2DM Yin deficiency and heat excess group,and 69 of them were significantly adjusted back by DHBY (53 down-regulated and 16 up-regulated). DHBY can effectively regulate glycerophospholipid metabolism,bile secretion,steroid degradation,primary bile acid biosynthesis,and other metabolic pathways in diabetic rats with Yin deficiency heat excess syndrome,and play a role in anti-Yin deficiency,and heat excess diabetes. Conclusion DHBY can effectively improve diabetic rats with Yin deficiency and heat excess syndrome,and regulate metabolic pathways such as glycerophospholipid metabolism,bile secretion,steroid degradation,and primary bile acid biosynthesis in diabetic rats with Yin deficiency and heat excess syndrome.
维普
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