Messenger RNA expression of monocyte chemoattractant protein-1 and interleukin-6 in stone-containing kidneys

Messenger RNA expression of monocyte chemoattractant protein-1 and interleukin-6 in stone-containing kidneys
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DOI:
10.1111/j.1464-410x.2008.07461.x
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发表时间:
2008-05-01
期刊:
影响因子:
4.5
通讯作者:
Tosukhowong, Piyaratana
Tosukhowong, Piyaratana
中科院分区:
医学2区
文献类型:
--
作者:
Boonla, Chanchai;Hunapathed, Chanutra;Tosukhowong, Piyaratana

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研究肾结石患者肾内单核细胞趋化蛋白-1(MCP-1)和白细胞介素-6(IL-6)mRNA的表达,并评价其表达是否与肾功能相关,因为氧化应激和炎症参与了肾结石的发病机制。收集29例肾结石患者的血和24小时尿标本。对照肾组织取自6例肾癌患者肾切除术的非癌和癌部分,对照24小时尿样取自30例健康受试者。测定校正肌酐清除率、尿N-乙酰-β-氨基葡萄糖苷酶活性和8-羟基脱氧鸟苷(8-OHdG)。采用真实的逆转录-聚合酶链反应检测组织中MCP-1和IL-6的mRNA表达,肾结石患者的肾小管损伤和氧化应激明显大于健康对照组。结石旁肾组织MCP-1和IL-6 mRNA的表达明显低于癌旁肾组织,但与非癌肾组织比较差异无统计学意义。在结石旁肾组织中,MCP-1 mRNA水平明显高于IL-6,但二者表达水平之间存在显著相关性。组织学检查显示,浸润的白细胞数量与肾内MCP-1和IL-6的mRNA水平相对应。肾结石合并肾功能损害患者肾内MCP-1和IL-6 mRNA水平显著高于肾功能正常者。此外,严重肾小管损伤患者的mRNA水平显著高于肾小管损伤较轻的患者。肾内mRNA表达与尿8-OHdG无相关性。肾结石与肾内轻度炎症相关。肾内MCP-1和IL-6 mRNA表达增加与肾损害加重相关。因此,MCP-1和IL-6的表达,至少部分,有助于肾结石的进展。
To investigate the intrarenal mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in patients with nephrolithiasis, and to evaluate whether their expression is associated with renal function, as oxidative stress and inflammation are involved in the pathogenesis of nephrolithiasis.Renal biopsies from near the stone, and blood and 24-h urine specimens were collected from 29 patients with nephrolithiasis. Control renal tissues were taken from non-cancerous and cancerous portions of nephrectomy from six patients with renal cancers, and control 24-h urine samples were obtained from 30 healthy subjects. Corrected creatinine clearance, urinary N-acetyl-beta-glucosaminidase activity and 8-hydroxy-deoxyguanosine (8-OHdG) were determined. The mRNA expressions of MCP-1 and IL-6 in the tissues were measured by real time reverse transcription-polymerase chain reaction.Patients with nephrolithiasis had significantly greater renal tubular damage and oxidative stress than the healthy controls. Intrarenal mRNA expressions of MCP-1 and IL-6 in stone-adjacent renal tissues were significantly lower than in cancerous renal tissues, but not statistically different from that in non-cancerous renal tissues. In stone-adjacent renal tissues, the mRNA level of MCP-1 was significantly higher than that of IL-6, but their expressions were significantly correlated with each other. Histological examination showed that the number of infiltrated leukocytes corresponded well with the intrarenal mRNA levels of MCP-1 and IL-6. Patients with nephrolithiasis and compromised renal function had significantly higher intrarenal mRNA levels of MCP-1 and IL-6 than those with preserved renal function. Also, the mRNA levels in patients with severe renal tubular damage were significantly greater than in those with less renal tubular damage. There was no association between intrarenal mRNA expression and urinary 8-OHdG.Nephrolithiasis was associated with low-grade intrarenal inflammation. A greater intrarenal mRNA expression of MCP-1 and IL-6 was associated with enhanced renal impairment. Thus, expression of MCP-1 and IL-6, at least in part, contributed to the progression of nephrolithiasis.