CXC趋化因子配体16在慢性肾脏病中的表达及其意义

目的：观察CXC趋化因子配体16（CXCL16）在慢性肾脏病（CKD）患者和CDK动物模型中的表达情况，研究其与肾功能等因素的相关性，探讨CXCL16在CKD进展中的作用。方法：在临床研究方面，收集200例CKD患者[按肾小球滤过率（eGFR）分为CKD 1-2期组、CKD 3-4期组和CKD 5期组]和40例健康对照组的外周血标本，检测血清肌酐、尿素氮、血脂、eGFR等各项指标，并检测血清中CXCL16的含量。在动物实验方面，取雄性C57BL/6小鼠14只，随机分为普通对照组及普通模型组（各7只），雄性CXCL16基因敲除小鼠7只，随机分为基因敲除对照组（3只）及基因敲除模型组（4只）。4周后处死小鼠，检测小鼠血清尿素氮、肌酐、CXCL16等指标，观察肾组织病理改变。结果：健康对照组和CKD各期组患者之间年龄、性别、体质量指数（BMI）差异无统计学意义（P＞0.05）。CKD 5期组患者血清CXCL16水平高于健康对照组和CKD 1-2期组、CKD 3-4期组，差异均有统计学意义（P＜0.05）。在校正了CKD患者的年龄、性别、BMI后，eGFR、C-反应蛋白（CRP）和脂联素与血浆CXCL-16独立相关。在动物实验中，CXCL基因敲除模型组与普通模型组相比，其血清尿素氮、肌酐及尿酸升高幅度偏低；肾脏病理提示基因敲除模型组小鼠肾脏损伤程度轻于普通模型组。结论：随着CKD的进展，血浆中CXCL-16的水平显著升高，并与肾功能的变化独立相关。

Expression and significance of CXCL-16 in chronic kidney disease

Objective: To study the effect of C-X-C chemokine ligand 16 (CXCL16) in patients with chronic kidney disease (CKD) and animal models of nephritic syndrome. To investigate whether elevated CXCL16 concentrations were associated with renal failure in the development of CKD. Methods: Serum samples of 40 healthy people and 200 CKD subjects including our patients and long-term hemodialytic patients were collected. Plasma CXCL16 levels and other clinical and biochemical parameters in all subjects were obtained based on the clinical examinational standard methods. As for experimental animals, 14 male C57BL/6 rats were obtained, which were distributed into common control group and common model group. 7 CXCL16 knockout rats which were randomly distributed into knockout control group and knockout model group were also obtained. Their living conditions were observed for 4 weeks. After that, they were killed and their serum urea nitrogen, creatine, CXCL16 and other indexes were determined; the pathological changes of their kidney tissues were observed. Results: Plasma CXCL16 levels were significantly increased with the development of CKD from early-and end-stage (P<0.001 for trend), median circulating CXCL16 level was higher in end-stage CKD patients compared with the early-stage CKD patients and the middle-stage CKD patients. After adjusting for age, gender, and body mass index (BMI), plasma CXCL-16 levels significantly associated with renal function and other factors in CKD subjects. Correlative analysis showed the level of CXCL16 was positively associated with serum urea nitrogen, serum creatine, CRP and adiponectin (P<0.05), and negatively associated with eGFR, HDL-C. In the animal experiments, compared with those in common model group, the increments of serum urea nitrogen, creatine and uric acid in knockout model group were much lower. Renal pathology indicated the level of kidney damage in knockout model group was lower than that in common model group. Conclusion: Plasma CXCL16 levels are significantly increased with the development of early-to end-stage CKD and are independently associated withthe loss of renal function. Understanding whether increased CXCL16 is a marker or a potential mechanism of myocardial hypertrophy in CKD requires further study.