Song Zhe, Zhao Yang, Wang Xian, Xu Ming-Jiang
Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing 100191, China.
The Department of Laboratory Medicine, Peking University Third Hospital, Beijing 100191, China.
Sheng Li Xue Bao. 2016 Dec 25;68(6):709-715.
The present study was aimed to explore the effects of hyperuricemia on vascular calcification in chronic renal failure (CRF) and the mechanisms. Adenine diet-induced CRF rat model was used. Twenty-three male 8-week-old Wistar rats were randomly divided into control group (Ctr, n = 5), CRF group (n = 8) and CRF plus allopurinol group (CRF + ALL, n = 10), and the rats were given standard diet plus standard drinking water, adenine diet plus standard drinking water and adenine diet plus allopurinol drinking for 6 weeks, respectively. Vascular calcification of abdominal aorta was identified by o-cresolphthalein complexone copper assay and Von Kossa staining. The mRNA expression levels of osteogenic/chondrogenic regulatory factors (Cbfα1, Msx2, Osx, and Sox9), vascular smooth muscle cell (VSMC) lineage markers (SM22a and Acta2) and calcification inhibitors (Mgp and Opn) were detected by real-time PCR. The results showed that the levels of serum phosphorus (Pi), urea nitrogen, creatinine and uric acid were significantly increased in the CRF rats, whereas allopurinol reversed the levels of serum urea nitrogen, creatinine and uric acid, except for serum Pi. The calcium content of rat abdominal aorta in the CRF group was significantly higher than that of the Ctr group (P < 0.05), but it was partially rescued in the CRF + ALL group (P < 0.05); Compared with the Ctr group, Cbfα1, Msx2, Osx and Sox9 mRNA levels of abdominal aorta in the CRF group were significantly up-regulated, while SM22a, Acta2, Mgp and Opn mRNA levels were down-regulated. In the CRF + ALL group, the changes of Msx2, Osx, SM22a and Opn mRNA levels were reversed (P < 0.05). Allopurinol had no effect on high Pi-induced VSMC calcification, and uric acid (6 and 7 mg/dL) significantly increased high Pi-induced VSMC calcification in vitro (P < 0.05). These results suggest that hyperuricemia in CRF may promote the osteoblast/chondrocyte-like cells differentiation of VSMC and further exacerbate vascular calcification.
本研究旨在探讨高尿酸血症对慢性肾衰竭（CRF）血管钙化的影响及其机制。采用腺嘌呤饮食诱导的CRF大鼠模型。将23只8周龄雄性Wistar大鼠随机分为对照组（Ctr，n = 5）、CRF组（n = 8）和CRF加别嘌呤醇组（CRF + ALL，n = 10），分别给予标准饮食加标准饮用水、腺嘌呤饮食加标准饮用水和腺嘌呤饮食加别嘌呤醇饮用水6周。采用邻甲酚酞络合铜法和Von Kossa染色法鉴定腹主动脉血管钙化。通过实时PCR检测成骨/软骨形成调节因子（Cbfα1、Msx2、Osx和Sox9）、血管平滑肌细胞（VSMC）谱系标志物（SM22a和Acta2）和钙化抑制剂（Mgp和Opn）的mRNA表达水平。结果显示，CRF大鼠血清磷（Pi）、尿素氮、肌酐和尿酸水平显著升高，而别嘌呤醇可使血清尿素氮、肌酐和尿酸水平恢复正常，但血清Pi水平除外。CRF组大鼠腹主动脉钙含量显著高于Ctr组（P < 0.05），而CRF + ALL组则部分恢复（P < 0.05）；与Ctr组相比，CRF组腹主动脉Cbfα1、Msx2、Osx和Sox9 mRNA水平显著上调，而SM22a、Acta2、Mgp和Opn mRNA水平下调。在CRF + ALL组中，Msx2、Osx、SM22a和Opn mRNA水平的变化得到逆转（P < 0.05）。别嘌呤醇对高Pi诱导的VSMC钙化无影响，而尿酸（6和7 mg/dL）在体外显著增加高Pi诱导的VSMC钙化（P < 0.05）。这些结果表明，CRF中的高尿酸血症可能促进VSMC向成骨细胞/软骨样细胞分化，进而加剧血管钙化。
