摘要
目的观察乳铁蛋白(lactoferrin,Lf)对自发性高血压大鼠(spontaneously hypertensive rats,SHR)血压的影响,并探讨肠道菌群所发挥的作用。方法27只雄性自发性高血压大鼠按体重随机分为模型组、低剂量乳铁蛋白干预组(低乳铁蛋白组)及高剂量乳铁蛋白干预组(高乳铁蛋白组);另外27只雄性自发性高血压大鼠,随机分为抗生素组、抗生素+低剂量乳铁蛋白干预组(抗生素低乳铁蛋白组)、抗生素+高剂量乳铁蛋白干预组(抗生素高乳铁蛋白组),均持续接受广谱抗生素饮水以清除内源性肠道菌群。低、高剂量乳铁蛋白分别为100和300 mg/kg,连续灌胃干预16周,每4周用智能无创血压计测量血压水平。实验结束后,酶联免疫吸附法测定血浆中血管紧张素转换酶、血管紧张素Ⅱ、内皮素、一氧化氮、一氧化氮合成酶水平;16S rDNA测序肠道菌群。结果干预16周后,与模型组相比,低、高乳铁蛋白组收缩压均明显降低(P<0.01),低乳铁蛋白组(P<0.01)和高乳铁蛋白组(P<0.05)血浆中血管紧张素转换酶水平显著低于模型组,低乳铁蛋白组乙酸产生菌相对丰度明显增加(P<0.05)。清除内源性肠道菌群后,3组的肠道菌群相对丰度、多样性均降至极低。抗生素低乳铁蛋白组、抗生素高乳铁蛋白组的血压和血管活性物质水平与抗生素组差异无统计学意义。结论乳铁蛋白干预降低血压的作用在清除肠道菌群后消失,提示乳铁蛋白可能通过调节肠道菌群发挥降压作用。
OBJECTIVE To observe the influence of lactoferrin(Lf)on blood pressure and investigate the role of gut microbiota in spontaneously hypertensive rats(SHR).METHODS According to the initial body weight,male SHR(n=27)were randomly divided into model group,low Lf group and high Lf group,another 27 SHR given antibiotics to reduce the native microbiota load and were randomly divided into antibiotic group,antibiotic-low Lf group and antibiotic-high Lf group.The treatment lasted 16 weeks and blood pressure was measured every 4 weeks.At the end of the experiment,the serum levels of angiotensin converting enzyme(ACE),angiotensinⅡ(AngⅡ),endothelin-1(ET-1),nitric oxide(NO)and nitric oxide synthase(NOS)were measured.16 S rDNA high-throughput sequencing was conducted and intestinal flora related indexes were analyzed.RESULTS At 16 weeks,SBP was significantly decreased in low Lf group and high Lf group than in the model group(P<0.01).Serum ACE was lower in low Lf group(P<0.01)and high Lf group(P<0.05)than model.Compared with model group,a significant increase in acetate-producing bacteria was observed in low Lf group(P<0.01).When the gut microbiota was eliminated with antibiotics,there were no significant difference of blood pressure and serum enzymes and vasoactive substances with Lf intervention.CONCLUSION Our findings indicated that the antihypertensive effect of Lf disappeared when the gut microbiota was eliminated with antibiotics.Thus,the gut microbiota is likely to play an important role in the antihypertensive effect of Lf.
作者
任锦锦
彭思敏
陈婧司
陆梦兰
万忠晓
徐加英
秦立强
Ren Jinjin;Peng Simin;Chen Jingsi;Lu Menglan;Wan Zhongxiao;Xu Jiaying;Qin Liqiang(Department of Nutrition and Food Hygiene,School of Public Health,Soochow University,Suzhou 215123,China;School of Radiology and Protection,Soochow University,Suzhou 215123,China)
出处
《卫生研究》
CAS
CSCD
北大核心
2022年第2期260-265,共6页
Journal of Hygiene Research
基金
国家自然科学基金(No.81973024,82173502,82073482)。
关键词
高血压
自发性高血压大鼠
血管紧张素转换酶
肠道菌群
hypertension
spontaneously hypertensive rats
agiotensin converting enzyme
gut microbiota