黄芩苷对血管紧张素Ⅱ诱导的高血压小鼠肠道屏障的干预作用

Effects of baicalin on the intestinal barrier impairment of hypertensive mice induced by angiotensin Ⅱ

目的:探讨黄芩苷对血管紧张素Ⅱ(AngⅡ)诱导的高血压小鼠肠道屏障损伤的干预效应。方法:将C57BL/6J小鼠随机分为5组,假手术组(Sham)组,模型组,黄芩苷低、中、高剂量组。除Sham组外,其余各组予AngⅡ持续微量输注4周造模,黄芩苷各组分别予相应剂量黄芩苷灌胃,连续干预4周。测量小鼠血压;HE、Masson染色观察肠道病理情况;免疫荧光标记ZO-1观察肠道黏膜上皮屏障;16S rDNA Amplicon测序技术评价肠道菌群的改变。结果:AngⅡ诱导3周后小鼠收缩压、舒张压显著升高(P<0.05);黄芩苷高剂量组收缩压、舒张压从第3周开始显著低于AngⅡ组(P<0.05);HE、Masson染色结果显示黄芩苷高剂量组显著抑制AngⅡ诱导的肠道上皮损伤和胶原纤维面积增加(P<0.05)。免疫荧光结果显示黄芩苷高剂量组显著抑制AngⅡ诱导的回肠、结肠上皮ZO-1表达减少(P<0.05);LEfSe差异分析提示,黄芩苷各剂量组对肠道多种菌属有明显影响。结论:黄芩苷能有效抑制AngⅡ诱导的高血压相关肠道屏障损伤,促进肠黏膜上皮紧密连接蛋白表达,同时调控肠道菌群。

Objective: To explore the protective effect of baicalin on the intestinal barrier barrier of hypertensive mice induced by angiotensinⅡ(AngⅡ). Methods: C57BL/6J mice were randomly divided into 5 groups, Sham group, AngⅡgroup low, medium, and high dose groups of baicalin. Except for the Sham, the rest of the groups were given AngⅡ osmotic pump for 4 weeks to create the model. Baicalin was given by gavage for 4 weeks. The blood pressure of mice were measured, HE and Masson staining was used to observe the pathological conditions of the intestines;Immunohistochemical method was used to observe the expression of tight junction protein ZO-1 in the intestinal mucosa epithelium. 16S rDNA Amplicon sequencing technology was used to evaluate the change of intestinal. Results: The SBP and DBP of the mice increased significantly from the third week in the AngⅡgroup(P<0.05), the SBP and DBP of the high dose group of baicalin were significantly lower than those of the AngⅡ group from the third week(P<0.05). HE and Masson staining showed that high dose group of baicalin significantly inhibited intestinal epithelial injury and collagen fiber area increase induced by AngⅡ(P<0.05). The results of immunohistochemical staining indicated that high dose group of baicalin significantly inhibited the decrease of ZO-1 expression induced by AngⅡ in ileum and colon epithelium(P<0.05). The LEfSe difference analysis suggests that each dose group of baicalin has a significant impact on a variety of intestinal flora. Conclusion: Baicalin can inhibit AngⅡ-induced hypertensionrelated intestinal barrier damage, and increase the expression of tight junction protein in the intestinal mucosal epithelium, and regulate the intestinal flora.