阻断CCR2信号对IgA肾病模型大鼠肾病理损伤及炎性因子表达的影响  

Effect of blocking CCR2 signal on renal pathological damage and expression of inflammatory factors in rats with IgA nephropathy

作　　者：沈雁婕 朱志清 王蕊 闫莉莉 鹿玲[2] 张琴[2] 任振华[1] SHEN Yan-jie;ZHU Zhi-qing;WANG Rui;YAN Li-li;LU Ling;ZHANG Qin;REN Zhen-hua(Neurobiological Institution,Anhui Medical University,Heifei 230032,China;Department of Pediatrics,First Affiliated Hospital of Anhui Medical University,Hefei 230022,China)

机构地区：[1]安徽医科大学神经生物学研究所,合肥230032 [2]安徽医科大学第一附属医院儿科,合肥230022

出　　处：《临床与实验病理学杂志》2021年第11期1307-1312,共6页Chinese Journal of Clinical and Experimental Pathology

基　　金：安徽高校自然科学研究项目(KJ2019A0245、KJ2019A0940)。

摘　　要：目的探讨阻断CCR2信号对IgA肾病(IgA nephropathy,IgAN)模型大鼠肾组织病理变化及炎性因子表达的影响。方法将40只Wistar大鼠随机分为正常对照组、IgAN模型组、CCR2拮抗剂组和奥美沙坦组。联合应用LPS、BSA和CCl4建立IgAN大鼠模型、CCR2拮抗剂组和奥美沙坦组,大鼠成模后分别予以10 mg/kg的CCR2拮抗剂或Olmesartan灌胃2周,正常对照组和IgAN模型组予以等量的生理盐水。测定24 h尿蛋白(NPr)、血尿素氮(BUN)、血肌酐(SCre)含量;采用免疫荧光、免疫组化、病理染色等方法检测IgAN模型组大鼠肾组织病理改变及炎性因子的表达。结果与正常对照组相比,IgAN模型组大鼠肾小球系膜区IgA沉积和系膜细胞增生明显,24 h NPr、SCre和BUN水平明显升高(P<0.01),CCR2拮抗剂能减少系膜区IgA沉积和系膜细胞增生,并能明显降低大鼠24 h NPr、SCre和BUN水平(P<0.01)。与正常对照组相比,IgAN模型组大鼠肾组织炎症相关因子MCP-1、IL-6、IL-17和TNF-α表达明显增强,CCR2拮抗剂能明显抑制上述炎症因子的表达(P<0.05)。结论阻断CCR2信号可缓解IgAN模型大鼠的肾组织病理损伤,并降低肾组织炎症因子的表达,提示CCR2信号通路可能参与IgAN的发生、发展。Purpose To explore the effect of blocking CCR2 signal on renal pathological damage and expression of inflammatory factors in rats with IgA nephropathy(IgAN).Methods Forty Wistar rats were randomly divided into normal control group,IgAN model group,CCR2 antagonist group and Olmesartan group.The IgAN rat model,CCR2 antagonist group and Olmesartan group were established by the combined application of LPS,BSA and CCl4,and the rats were given 10 mg/kg of CCR2 antagonist or Olmesartan by gavage for 2 weeks after modeling,and the normal control group and IgAN model group were given equal amounts of saline.24h urine protein(NPr),blood urea nitrogen(BUN),and serum creatinine(SCre)levels were meseaured.The pathological change of renal tissue and inflammatory factor expression in IgAN model group was examined by pathological staining,immunohistochemistry,immunofluorescence methods.Results Compared with control group,IgA deposition and mesangial cell proliferation in the glomerular mesangial area were significantly increased in the kidney tissues of IgAN model group,and the levels of 24 h Npr,SCre and BUN were also significantly increased(P<0.01).After blocking CCR2 signal by RS102895,IgA deposition,mesangial cell proliferation and the inflammatory factors were markedly reduced(P<0.01).Compared with control group,the expressions of MCP-1,TNF-α,IL-6 and IL-17 in the renal tissue of IgAN model rats were significantly increased,CCR2 antagonists could inhibit the levels of these inflammatory factors(P<0.05).Conclusion Blocking CCR2 can alleviate the renal pathological changes,and reduce the expression of inflammatory factors in the kidney tissue of IgAN model rats,suggesting that CCR2 signaling pathway may be involved in the occurrence and development of IgA nephropathy.

关 键 词：IGA肾病 CC趋化因子受体2 系膜细胞 炎症因子 大鼠 

分 类 号：R365[医药卫生—病理学]