佐剂性关节炎大鼠肾功能损伤及对肾脏有机阴离子转运体3表达的影响

Effects of adjuvant arthritis on renal function and expression of organic anion transporter 3 in rats

目的研究佐剂性关节炎(AA)对大鼠肾脏功能和肾脏有机阴离子转运体3(OAT3)表达的影响。方法在大鼠右侧后足趾皮内注射弗氏完全佐剂建立AA模型。固定时间点收集大鼠血液和尿液,观察肾损伤指标的动态变化。通过肾脏的HE染色切片观察肾损伤情况。免疫组化和Western blot检测肾皮质OAT3蛋白和炎性因子白介素-6(IL-6)、白介素-1β(IL-1β)及肿瘤坏死因子-α(TNF-α)的表达水平。结果与正常组相比,AA大鼠关节炎指数评分、继发性足爪肿胀、关节肿胀数、全身评分均显著增加(P<0.05)。X线检测结果显示,AA模型大鼠足爪骨关节出现软组织水肿以及骨畸形的特征。生化指标显示,AA大鼠的肾损伤指标出现明显异常。免疫组化与Western blot结果显示,AA大鼠肾皮质OAT3的表达水平显著降低,同时炎性因子IL-6、TNF-α和IL-1β的表达水平明显升高(P<0.05)。结论AA大鼠的肾功能损伤可能与肾脏OAT3的表达降低及炎性因子表达升高有关。

Objective To investigate the effects of adjuvant arthritis(AA)on renal function and the expression of organic anion transporter 3(OAT3)in rats.Methods The AA model was established via intradermal injection of Freund′s complete adjuvant into the right hind toe of the rats.Blood and urine were collected at fixed time points to observe the dynamic changes of renal injury indicators.The kidney injury was observed by HE staining.Immunohistochemistry and Western blot were used to detect the expression levels of OAT3 protein and inflammatory factors interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in renal cortex.Results Compared with the normal group,the arthritis index score,the secondary paw swelling,the number of joint swelling,and the whole body score of AA rats significantly increased(P<0.05).The X-ray results showed that the AA model rats had soft tissue edema and bone deformity.Biochemical indicators showed that the renal injury indicators of AA rats were significantly abnormal.The results of immunohistochemistry and Western blot showed that the expression level of OAT3 in renal cortex of AA rats significantly decreased,while the expression levels of inflammatory factors IL-6,TNF-αand IL-1βsignificantly increased(P<0.05).Conclusion The renal injury of AA rats may be related to the decreased expression level of OAT3 and the increased expression level of inflammatory factors in kidney.