目的 探究药食同源中药复方（葛根、夏枯草、杜仲叶、菊花、山楂、芹菜）对两肾一夹（2 kidneys and 1 clip，2K1C）型高血压大鼠血压、肠道菌群结构和血清代谢物的调控作用。方法 2K1C型高血压大鼠随机分为模型组、氯沙坦（0.3 mg/kg）组和药食同源中药复方低、中、高剂量（0.5、2.5、5.0 mg/kg）组，每组7只。连续给药6周后，取眼周血，采用全自动生化分析仪检测各组大鼠血清相关指标；采用16S rDNA测序技术分析各组大鼠肠道菌群变化；采用苏木素-伊红（HE）染色观察各组大鼠肝脏和肾脏组织病理变化；采用高效液相质谱检测各组大鼠血清代谢产物变化。结果 药食同源中药复方干预6周后，大鼠血压明显下降（P<0.05、0.001），血清中总胆红素（total bilirubin，TBIL）和直接胆红素（direct bilirubin，DBIL）水平显著降低（P<0.05）。16S rDNA测序结果显示，在门水平上，大鼠肠道微生物群落的主要结构由厚壁菌门（Firmicutes）、拟杆菌门（Bacteroidetes）、变形菌门（Proteobacteria）、放线杆菌门（Actinobacteria）和酸杆菌门（Acidobacteria）组成，其中与模型组比较，药食同源中药复方组拟杆菌门相对丰度升高，厚壁菌门相对丰度降低；在属水平上主要由乳酸杆菌属Lactobacillus、肠球菌属Enterococuus、布劳特氏菌属Blautia、罗姆布茨菌属Romboutsia和丁酸弧菌属Anaerostipes组成，药食同源中药复方组乳酸杆菌属相对丰度明显高于模型组。各组大鼠血清代谢产物存在明显差异，筛选得到143个差异性血清代谢产物。药食同源中药复方组血清中牛磺胆酸、L-抗坏血酸、焦谷氨酸、苯乙酰甘氨酸水平显著上调，甘氨胆酸水平显著下调。组织病理切片结果表明，药食同源中药复方干预可修复高血压造模造成的腹主动脉及肾脏结构性损伤，进一步修复腹主动脉及肾脏的功能。结论 药食同源中药复方可通过改善2K1C型高血压大鼠肠道菌群结构，调节血清代谢产物，从而发挥对高血压的治疗作用。

Objective To study the regulation of blood pressure, intestinal flora structure and serum metabolites of 2 kidneys and 1 clip (2K1C) hypertension rats by the intervention of medicine and food homologous Chinese medicine formula[MFHCMF, including Gegen (Puerariae Lobatae Radix), Xiakucao (Prunellae Spica), Duzhongye (Eucommiae Folium), Juhua (Chrysanthemi Flos), Shanzha (Crataegi Fructus), Hanqin (Apium graveolens)]. Methods 2K1C hypertension rats were randomly divided into model group, losartan (0.3 mg/kg) group, and MFHCMF low-, medium-, high-dose (0.5, 2.5, 5.0 mg/kg) groups, with seven rats in each group. After continuous administration for six weeks, periocular blood was collected and serum related indicators of rats in each group were detected using a fully automated biochemical analyzer; 16S rDNA sequencing technology was used to analyze the changes in gut microbiota of rats in each group; Pathological changes in liver and kidney tissues of rats in each group were observed by hematoxylin eosin (HE) staining; High performance liquid chromatography mass spectrometry was used to detect changes in blood metabolites of rats in each group. Results After six weeks of intervention with MFHCMF, the blood pressure of rats was significantly decreased (P < 0.05, 0.001), and the levels of total bilirubin (TBIL) and direct bilirubin (DBIL) in serum were significantly decreased (P < 0.05). 16S rDNA sequencing results showed that at the phylum level, the main structure of the gut microbiota in rats was composed of Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Acidobacteria. Compared with model group, the relative abundance of Bacteroidetes in MFHCMF group was increased, while the relative abundance of Firmicutes was decreased. At the genus level, the main structure of the gut microbiota in rats was composed of Lactobacillus, Enterococcus, Blautia, Romboutsia and Anaerostipes. The abundance of Lactobacillus in MFHCMF group was significantly higher than that in model group. There were significant differences in serum metabolites among different groups of rats, and a total of 143 differential serum metabolites were screened. The levels of taurocholic acid, L-ascorbic acid, pyroglutamic acid and phenylacetylglycine in serum of MFHCMF group were significantly upregulated, while the level of glycocholic acid was significantly downregulated. The results of tissue pathological sections indicated that the intervention of MFHCMF could repair the structural damage to the abdominal aorta and kidneys caused by hypertension modeling, further repairing the function of the abdominal aorta and kidneys. Conclusion MFHCMF can improve the intestinal microbiota structure of 2K1C type hypertensive rats, regulate serum metabolites, and thus exert a therapeutic effect on hypertension.

R285.5

国家自然科学基金资助项目（81602848）