摘要： 目的 探讨羟氯喹对IgA肾病（IgAN）大鼠Toll样受体4（TLR4）表达的影响及其对肾脏病理的改善作用。方法 将24只Wistar大鼠随机分为对照组、IgAN组、羟氯喹治疗组（HCQ组），每组8只。IgAN组和HCQ组采用牛血清白蛋白+蓖麻油+脂多糖+CCl4的方法建立IgAN模型，9周后HCQ组大鼠每日给予羟氯喹灌胃，IgAN组和对照组大鼠每日给予蒸馏水灌胃，持续8周。第17周末处死大鼠，留取肾组织标本。肾组织切片行苏木素-伊红染色和Masson染色，观察羟氯喹治疗前后IgAN大鼠肾小球系膜细胞增生和肾组织纤维化情况；采用直接免疫荧光法检测肾小球系膜区IgA的沉积密度；采用免疫组织化学染色法观察肾组织中TLR4的表达。结果 IgAN组与对照组相比，肾组织内炎症细胞浸润明显增多、系膜细胞明显增生、肾组织明显纤维化，系膜区IgA沉积密度和TLR4阳性表达率均明显增加，差异均有统计学意义（P<0.05）。HCQ组与IgAN组相比，肾组织内炎症细胞浸润、系膜细胞增生、肾组织纤维化程度均减轻，系膜区IgA沉积密度和TLR4阳性表达率均降低，差异均有统计学意义（P<0.05）；HCQ组与对照组相比，肾脏病理损伤仍较明显，系膜区IgA沉积密度和TLR4阳性表达率均明显增加（P<0.05）。结论 羟氯喹对IgAN大鼠的肾脏病理损伤有改善作用，可能通过降低TLR4表达进而减轻肾内系膜增生和纤维化，减少IgA沉积，对IgAN有治疗作用。

羟氯喹对IgA肾病大鼠肾脏病理和Toll样受体4表达的影响

李优, 姜红, 李维

中国医科大学附属第一医院儿科, 沈阳 110001

收稿日期:2020-03-18出版日期:2020-11-30发布日期:2020-10-31
通讯作者:李维E-mail:Liwei_vivian@aliyun.com
作者简介:李优(1993-),女,医师,硕士研究生.
基金资助:辽宁省教育厅科学研究一般项目（L2015575）


关键词: IgA肾病, 肾脏, 羟氯喹, Toll样受体4
Abstract: Objective To investigate the therapeutic effects of hydroxychloroquine (HCQ) on the expression of Toll-like receptor 4 (TLR4) and the renal pathology in a rat model of IgA nephropathy (IgAN). Methods Twenty-four Wistar rats were divided into three groups (each n=8):the control,IgAN,and HCQ groups. The rats in the IgAN and HCQ groups were treated with bovine serum albumin, castor oil,lipopolysaccharide,and CCl4 for 9 weeks to establish the IgAN model. In the HCQ group,the rats were then administered HCQ for 8 weeks. At the end of week 17,the rats were sacrificed and renal tissue samples were collected. The proliferation of mesangial cells and the renal fibrosis were observed by hematoxylin-eosin staining and Masson staining. The intensity of IgA deposition and the expression of TLR4 were detected by using a direct immunofluorescence assay and immunohistochemical staining. Results Compared with the control group, the IgAN group showed a significant increase in the infiltration of renal inflammatory cells,the proliferation of mesangial cells,the degree of renal fibrosis,and the intensity of IgA deposition and TLR4 expression in the mesangial region (P<0.05). Treatment with HCQ reduced the intensity of IgA deposition and TLR4 expression,alleviated the degree of renal fibrosis,and improved pathological changes compared with the IgAN group (P<0.05). There were significant differences in renal pathology,intensity of IgA deposition,and TLR4 expression between the HCQ and control groups (P<0.05). Conclusion HCQ ameliorated the pathological changes in IgAN rats through the inhibition of TLR4 expression,which alleviated mesangial hyperplasia and fibrosis and reduced IgA deposition to exert therapeutic effects.
Key words: IgA nephropathy, kidney, hydroxychloroquine, Toll-like receptor 4
PDF全文下载地址:

https://journal.cmu.edu.cn/CN/article/downloadArticleFile.do?attachType=PDF&id=2632