摘要
目的探讨高尿酸血症对足细胞的影响及其机制研究。方法 48只雄性SD大鼠随机分成正常对照组(NC)、模型组(MG)、别嘌呤醇组(ALLO)及雷公藤甲素(Triptolide, TP)干预组(TP),每组12只。定期检测大鼠血尿酸(sUA)、肌酐(Scr)、尿素氮(BUN)及24h尿蛋白排泄量(24 h UPT),光镜、电镜观察肾组织病理学及足细胞病变情况,免疫组化、Real time PCR及Western blot技术检测足细胞nephrin以及肾组织IL-1β表达情况。结果与对照组相比,造模第4周、8周后,模型组大鼠的sUA、Scr、BUN及24 h UPT均明显升高(P<0.01);造模8周后,模型组大鼠肾IL-1β表达增加、nephrin表达减少(P<0.01),肾小球基底膜不规则增厚、上皮细胞肿胀、足突融合、肾间质炎细胞浸润。雷公藤甲素干预后,大鼠sUA、Scr、BUN及24 h UPT水平下降,足细胞上述病理性改变明显缓解,且IL-1β表达下调,nephrin表达增加,与模型组比较差异具有显著性(P<0.01)。结论高尿酸血症可能导致大鼠足细胞相关蛋白nephrin及肾组织IL-1β表达异常,进而出现肾损害。
Objective To investigate the effect of hyperuricemia on podocytes and its related mechanism. Methods Forty-eight male SD rats were randomly divided into normal control group(NC), model group(MG), allopurinol group(ALLO) and Triptolide(TP) intervention group(TP) with 12 rats in each group. The sUA, Scr, BUN And 24 h urine protein(24 h UPT) level of rats were regularly tested. Renal histopathology and podocyte lesions were observed under light microscope and electron microscope. Immunohistochemistry, Real-time PCR and Western blot were used to detect the expression of IL-1β in podocytes and renal tissues. Results After 4 weeks and 8 weeks of modeling, the SUA, SCR, BUN and 24 h UPT of model group were significantly higher than those of control group(P<0.01). After 8 weeks of modeling, the expression of IL-1β was increased and the expression of Nephrin was decreased in the model group, which was significantly different from that in the control group(P<0.01).The irregular thickening of glomerular basement membrane, swelling of epithelial cells, fusion of foot processes and infiltration of renal interstitial inflammatory cells were observed under electron microscope. After treatment with triptolide, the levels of SUA, SCR, BUN and 24 h UPT were decreased, and the pathological changes of podocytes were significantly alleviated, the expression of IL-1β was down-regulated, and the expression of Nephrin was increased, with significant difference compared with model group(P<0.01). Conclusion Hyperuricemia may lead to abnormal expression of nephrin, a podocyte related protein, and IL-1β in renal tissues in rats, leading to renal damage.
作者
桑苗苗
吴伟斌
高琴
尹晓丽
陈卫东
张继强
SANG Miao-miao;WU Wei-bin;GAO Qin;YIN Xiao-li;CHEN Wei-dong;ZHANG Ji-qiang(Department of Nephrology,First Affiliated Hospital of Bengbu Medical College,Bengbu Medical College,233000 Bengbu,China;Department of physiology,Bengbu Medical College,233000 Bengbu,China)
出处
《解剖科学进展》
CAS
2021年第6期718-722,共5页
Progress of Anatomical Sciences
基金
2020年度安徽高校自然科学研究项目(KJ2020A0592)
2019年度蚌埠市科技创新指导类项目及蚌埠医学院科技发展基金(BYKF1410)
蚌埠医学院研究生科研创新计划项目(Bbycy1982)。
