大黄素对急性肾损伤大鼠肠道菌群的调节作用

Effect of emodin on gut microbiota of rats with acute kidney failure

该文研究大黄素对急性肾损伤(AKI)大鼠肠道菌群的调节作用。36只健康雄性大鼠随机分为正常组、模型组、阳性对照组(盐酸贝那普利5 mg·kg^(-1))和大黄素低(10 mg·kg^(-1))、中(25 mg·kg^(-1))、高(50 mg·kg^(-1))剂量组。除正常组外,其余各组采用腹腔注射硫酸庆大霉素损伤肾组织构建急性肾损伤模型,连续注射7 d,1次/d,腹腔注射2 h后,除模型组和正常组用生理盐水灌胃,其余各组分别用相应剂量药物灌胃给药,持续给药15 d。收集各组大鼠尿液和粪便分别测定尿蛋白总量和4种菌属含量;采集各组大鼠血液进行血液生化指标测定; HE染色观察各组大鼠肾脏组织形态学改变。结果显示,与正常组相比,模型组体质量、尿蛋白总量(UTP)、血浆细菌内毒素、尿素氮(BUN)、肌酐(SCr)、血清D-乳酸水平以及4种细菌含量均有显著变化(P<0. 05);与模型组相比,阳性对照组和大黄素各剂量组尿蛋白总量、尿素氮、血清D-乳酸水平、肌酐和血浆细菌内毒素均有所下降,以大黄素高剂量组下降最为显著(P<0. 01),肾脏病理修复情况最好;除大黄素低剂量组外,各给药组大肠杆菌及肠球菌数量显著下降(P<0. 05),乳酸菌及双歧杆菌明显升高(P<0. 05),以大黄素高剂量组变化最为明显(P<0. 01)。研究发现急性肾损伤大鼠(AKI)存在较明显的肠道菌群失调,大黄素对AKI大鼠肠道菌群失衡有一定的调节作用,这可能是其治疗急性肾损伤的作用机制之一。

The aim of this paper was to investigate the effect of emodin on gut microbiota in acute kidney injury rats ( AKI). Rats were randomly divided into several groups: normal group, model group, low-dose of emodin group ( 10 mg· kg^-1 ), medium-dose of emodin group (25 mg ·kg^-1 ), high-dose of emodin group ( 50 mg· kg^-1 ) and control group ( 5 mg ·kg^- 1 of benazepril hydrochloride). The AKI model rats were established by intraperitoneal injection of small dose of gentamicin sulfate for 7 days. Two hours after intraperitoneal injection, except for the nornial group and the model group, the other groups were given corresponding doses of drugs for 15 days. The serum levels of serum creatinine ( SCr), urea nitrogen ( BUN), plasma endotoxin level, 24 h urinary protein and D-lactate in the plasma were determined by sarcosine oxidase, urease method, tai reagent method, bromo cresol chloroform method and double antibody sandwich enzyme-linked immunoadsorbent assay, respectively. Gut microbial communities were assayed by fluorescent quantitative PCR methods. HE staining was used to detect the pathological changes of the kidneys. Compared with the normal group, there were significant differences in body weight, urinary protein ( UTP), bacterial endotoxin, urea nitrogen, creatinine, D-lactate in the plasma and four bacterial contents in the model group ( P<0. 05). The urinary protein, urea nitrogen, D-lactate, creatinine and plasma bacterial endotoxin in control group and each emodin group were lower than those in model group, especially for high-dose of emodin (P<0. 01). Moreover, pathology resolution in high-dose emodin was better than other groups. Except for low-dose of emodin group, qRT-PCR data suggested that the amounts of Escherichia coli and Enterococcus in medication administration group were increased, while the amounts of Lactobacilli and Bifidobacterium were reduced compared with model group (P<0. 05), especially for high-dose of emodin (P<0. 01). There is a clear imbalance of gut microbiota in rats with AKI. Emodin could regulate the imbalance of gut microbiota , which might be one of the mechanisms of its effects on AKI rats.