摘要
目的观察补虚祛湿消癥方(BXQSXZ)对免疫球蛋白A肾病(IgAN)大鼠的治疗效果,并探讨其作用机制。方法将25只雄性SD大鼠分为正常对照组、模型组、贝那普利(阳性对照药物)组、低剂量BXQSXZ组和高剂量BXQSXZ组,每组5只。采用免疫原口服、四氯化碳皮下注射和脂多糖静脉注射方法建立IgAN大鼠模型。各组大鼠分别灌胃给药4周后,检测24 h尿蛋白(UTP)、血清尿素氮(BUN)、肌酐(Cr)、IgA1相关免疫因子水平。分离大鼠肾组织,免疫荧光染色检测肾组织IgA含量;苏木精-伊红染色观察肾组织病理变化。肾组织匀浆后,检测肾脏炎症因子水平;采用实时聚合酶链反应法和蛋白质印迹法检测核心1β1,3-半乳糖基转移酶(C1GALT1)及其伴侣蛋白(COSMC)表达水平。结果与正常对照组比较,模型组大鼠肾小球系膜区大量IgA沉积。与模型组比较,高剂量BXQSXZ组肾组织IgA含量明显减少;血清IgA1、半乳糖缺陷型IgA1、B细胞活化因子及增殖诱导配体水平均降低(均P<0.05);UTP、Cr和BUN水平均降低(均P<0.05);肾小球、肾间质病变改善;肾组织中Toll样受体4、肿瘤坏死因子-α、白细胞介素(IL)-6、IL-4水平均降低(均P<0.05),IL-10、γ-干扰素水平均升高(均P<0.05);肾组织C1GALT1、COSMC mRNA及蛋白表达水平均升高(均P<0.05)。结论BXQSXZ能抑制IgAN大鼠肾组织IgA相关免疫复合物产生和沉积,改善尿蛋白、肾功能及肾组织病变,减轻肾脏炎症反应,其机制可能与恢复C1GALT1和COSMC表达有关。
Objective To explore the efficacy and mechanism of the Buxu Qushi Xiaozheng Formula(BXQSXZ)on a rat model of immunoglobulin A nephropathy(IgAN).Methods Twenty-five male SD rats were divided into negative control group,model group,positive control group(Benazepril),low-dose BXQSXZ group,and high-dose BXQSXZ group,5 rats for each.The IgAN rat model was established using oral immunogen,subcutaneous injection of carbon tetrachloride,and intravenous injection of lipopolysaccharide.After 4 weeks of gavage administration,24-hour urinary total protein(UTP),blood urea nitrogen(BUN),creatinine(Cr),IgA1-related immune factors in each group were measured.Kidney tissue was isolated,and immunofluorescence staining was used to detect IgA content in the kidney.Hematoxylin and eosin staining was performed to observe pathological changes in kidney tissue.After homogenizing kidney tissue,the levels of inflammatory factors in kidney tissue were measured.Expression levels of core 1β1,3-galactosyltransferase(C1GALT1)and its chaperone protein(COSMC)were detected by real-time polymerase chain reaction and Western blot.Results Compared to the normal control group,a large amount of IgA deposition was observed in the glomerular mesangial area of the model rats.Compared to the IgAN model group,the high-dose BXQSXZ group showed reduced renal IgA content in kidney tissue,decreased serum levels of IgA1,galactose-deficient IgA1,B-cell-activating factor,and proliferation-inducing ligand(all P<0.05),and lowered UTP,Cr,and BUN levels(all P<0.05),as well as improved glomerular and interstitial lesions,reduced levels of Toll-like receptor 4,tumor necrosis factor-α,interleukin-6(IL-6),and IL-4 in kidney tissues(all P<0.05),and elevated IL-10 and interferon-γlevels(all P<0.05).Additionally,C1GALT1 and COSMC mRNA and protein expression in kidney tissues were all elevated(all P<0.05).Conclusion BXQSXZ can inhibit the production and deposition of IgA-related immune complexes in the kidney tissue of IgAN rats,improve urinary protein,renal function,and kidney tissue lesions,and alleviate renal inflammatory responses,possibly by restoring the expressions of C1GALT1 and COSMC.
作者
邢洁
高骏伟
谢文佳
蔡旭东
XING Jie;GAO Junwei;XIE Wenjia;CAI Xudong(Department of Nephrology,Ningbo Municipal Hospital of Traditional Chinese Medicine,Affiliated to Zhejiang Chinese Medical University,Ningbo 315010,China)
出处
《浙江医学》
2025年第12期1277-1283,I0008,共8页
Zhejiang Medical Journal
基金
浙江省中医药科技计划项目(2023ZL152)
浙江省中医药重点学科建设项目(2024-XK-63)
宁波市中医肾病临床医学研究中心重大攻关项目(2024L001)。
