Gut Bacterial Translocation Contributes to Microinflammation in Experimental Uremia

Gut Bacterial Translocation Contributes to Microinflammation in Experimental Uremia
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DOI:
10.1007/s10620-012-2242-0
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发表时间:
2012-11-01
影响因子:
3.1
通讯作者:
Cheng, Shaoli
Cheng, Shaoli
中科院分区:
医学3区
文献类型:
--
作者:
Wang, Feiqian;Zhang, Pan;Cheng, Shaoli

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慢性尿毒症伴病理性肠道改变常发生微炎症。然而,尿毒症患者肠道细菌易位与微炎症之间的关系尚未得到广泛研究。本研究旨在探讨实验性尿毒症是否发生肠道菌群失调和易位,以及它们是否因此导致微炎症。40只大鼠行手术肾肿块5/6消融。取存活大鼠(尿毒症组,n = 21)和健康大鼠(假手术组,n = 20)进行实验。术后血液、肝脏、脾脏和肠系膜淋巴结(MLNs)进行细菌16S核糖体DNA扩增以确定是否存在细菌。用从血液、肝脏和脾脏中获得的细菌的16S rRNA序列设计的特异性引物扩增MLNs和结肠的细菌基因组DNA样本。使用焦磷酸测序分析每个受试者的结肠微生物组。测定肠对Tc-99m-DTPA、血浆hs-CRP、IL-6的通透性。在尿毒症组的一些大鼠中检测到肠外部位的细菌DNA和改变的结肠微生物组。通过从同一个体的血液、肝脏和脾脏中观察到的细菌物种特异性引物,获得MLNs和结肠中的细菌基因组DNA。尿毒症组肠通透性、血浆hs-CRP、IL-6水平均高于假手术组。血液中含有细菌DNA的尿毒症大鼠血浆hs-CRP和IL-6明显高于没有细菌DNA的大鼠。发生肠道菌群失调,细菌转移到全身和淋巴循环,从而导致实验性尿毒症的微炎症。
Microinflammation frequently develops in chronic uremia with pathological intestinal changes. However, the relationship between gut bacterial translocation and microinflammation in uremia has not been widely investigated.This study aimed to investigate whether gut microbiome dysbiosis and translocation occurred in experimental uremia, and whether they consequently contributed to microinflammation.Forty rats underwent surgical renal mass 5/6 ablation. The surviving (uremic group, n = 21) and healthy (sham group, n = 20) rats were used in the experiment. Postoperative blood, livers, spleens, and mesenteric lymph nodes (MLNs) were subjected to bacterial 16S ribosomal DNA amplification to determine if bacteria were present. Bacterial genomic DNA samples from the MLNs and colon were amplified with specific primers designed by the 16S rRNA sequence of the species obtained from blood, livers, and spleens. Pyrosequencing was used to analyze the colonic microbiome of each subject. Intestinal permeability to Tc-99m-DTPA, plasma hs-CRP, and IL-6 were measured.Bacterial DNA in extraintestinal sites and altered colonic microbiomes were detected in some rats in the uremic group. Bacterial genomic DNA in MLNs and colon were obtained by primers specific for bacterial species observed from blood, livers, and spleens of identical individuals. Intestinal permeability, plasma hs-CRP, and IL-6 levels were statistically higher in the uremic group compared with the sham group. Plasma hs-CRP and IL-6 were significantly higher in uremic rats with bacterial DNA in their blood than in those without.Gut microbiome dysbiosis occurs and bacteria translocate to the systemic and lymph circulation, thereby contributing to microinflammation in experimental uremia.