Yano Hirofumi, Tamura Yoshifuru, Kobayashi Kana, Tanemoto Masayuki, Uchida Shunya
Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan.
Clin Exp Nephrol. 2014 Feb;18(1):50-5. doi: 10.1007/s10157-013-0806-8. Epub 2013 Apr 13.
Uric acid (UA) remains a risk factor of chronic kidney disease (CKD). Therefore, it is important to clarify the mechanism of UA excretion in CKD. The specific mechanisms of extrarenal excretion from the intestine are unknown. We evaluated the expression of the UA transporter in the intestinal tract--the ATP-binding cassette transporter G2 (ABCG2)--in a 5/6 nephrectomy rat model of CKD.
Male Wistar rats (6 weeks old) were randomly assigned to the 5/6 nephrectomized (Nx) group or the sham-operated control group. Urine and blood samples were collected every 4 weeks. All the rats were killed at 8 weeks to obtain liver, duodenum, jejunum, ileum, and transverse colon tissues. Uricase activity was measured in the liver. Expression of ABCG2 in intestinal mucosa was measured with real time polymerase chain reaction (PCR).
The Nx group showed significantly decreased urine UA excretion/body weight and UA clearance compared to the control group at 4 and 8 weeks after nephrectomy. In contrast, serum UA and uricase activity were not significant. The expression of ABCG2 in the ileum of the Nx group showed significantly increased upregulation, while no changes were seen in the intestines of the control group.
The Nx rats exhibited lower excretion of urine UA and over-expression of ABCG2 in the ileum. The fact that serum UA did not increase despite the decrease in UA excretion suggests that an excretory pathway other than the kidney, probably the intestine, may operate in a complementary role that corroborates the increase in ABCG2 expression in the ileum.
尿酸（UA）仍然是慢性肾脏病（CKD）的一个危险因素。因此，阐明CKD中UA排泄的机制很重要。肠道肾外排泄的具体机制尚不清楚。我们在CKD的5/6肾切除大鼠模型中评估了肠道中UA转运体——ATP结合盒转运体G2（ABCG2）的表达。
将6周龄雄性Wistar大鼠随机分为5/6肾切除（Nx）组或假手术对照组。每4周采集尿液和血液样本。所有大鼠在8周时处死，获取肝脏、十二指肠、空肠、回肠和横结肠组织。测定肝脏中的尿酸酶活性。用实时聚合酶链反应（PCR）测量肠道黏膜中ABCG2的表达。
与对照组相比，Nx组在肾切除后4周和8周时尿UA排泄/体重和UA清除率显著降低。相比之下，血清UA和尿酸酶活性无显著变化。Nx组回肠中ABCG2的表达显著上调，而对照组肠道中未见变化。
Nx大鼠尿UA排泄降低，回肠中ABCG2过表达。尽管UA排泄减少，但血清UA并未升高，这一事实表明，除肾脏外的另一条排泄途径，可能是肠道，可能起到了补充作用，这与回肠中ABCG2表达增加相一致。
