免疫炎症性肾小管间质损伤在马兜铃酸肾病小鼠模型中的表现及作用  

The expression and function of immune inflammatory renal tubular intersitital injury in aris-tolochic acid nephropathy mice model

作　　者：毕玉娜 全伟 李晓忠[2] Bi Yuna;Quan Wei;Li Xiaozhong(Department of Pediatrics,Shandong Provincial Maternal and Child Health Care Hospital,Jinan 250014,China;Department of Nephrology and Immunology,Children's Hospital of Soochow University,Suzhou 215003,China)

机构地区：[1]山东省妇幼保健院儿科,济南250014 [2]苏州大学附属儿童医院肾脏免疫科,苏州215003

出　　处：《国际泌尿系统杂志》2022年第4期682-687,共6页International Journal of Urology and Nephrology

基　　金：国家自然科学基金(81370787);江苏省临床医学科技专项项目(BL2014052)。

摘　　要：目的研究免疫炎症性肾小管间质损伤在一种快速稳定的马兜铃酸肾病(AAN)小鼠模型中的表现并探讨其作用.方法将20只雌性C57BL/6小鼠随机分为5 d对照组(C5d)、15 d对照组(C15d)、5 d AAN组(F5d)和15 d AAN组(F15d),每组小鼠5只.采用马兜铃酸15 mg·(kg·d)^(-1)连续3 d腹腔注射建立AAN小鼠模型.采用苏木精-伊红(HE)和Mas-son染色观察小鼠肾组织的病理改变;免疫组化检测CD3、F4/80和Ly6G以评估肾组织免疫炎性细胞浸润情况;检测α平滑肌肌动蛋白(α-SMA)、成纤维细胞特异蛋白1(FSP-1)、Ⅰ型胶原α1链(col1α1)以评估肾脏的纤维化情况.结果ANN组小鼠的体重较对照组下降(P<0.05).与对照组比较,ANN组小鼠的血清尿素氮、肌酐水平均升高(均P<0.001).F5d组小鼠出现肾小管上皮细胞肿胀、空泡变性,F15d组小鼠出现细胞萎缩,管腔扩张,腔内透明管型形成;CD3和F4/80在F5d组小鼠中未见表达,而在F15d组小鼠中显著表达;FSP-1在F5d组小鼠中出现表达,并逐渐增强,α-SMA在F15d组中出现明显表达;F5d组和F15d组均未见col1a1表达,对照组均无上述指标表达.结论AAN小鼠模型较好地模拟了AAN的病理发展变化;免疫炎症性肾小管间质损伤存在于AAN小鼠模型的病理过程中,肾间质早期纤维化变化甚至要早于显著的免疫炎性细胞浸润,可能与损伤后的肾小管上皮细胞转分化为成纤维细胞有关.Objective To investigate the expression of immune inflammation and renal tubular intersitital injury in aristolochic acid nephropathy(AAN)mice model.Methods Twenty-five male C57BL/6 mice were divided into 5 groups:5-day control group(C5d),15-day control group(C15d),5-day AAN group(F5d)and 15-day AAN group(F15d),5 mice in each group.The AAN mice model was established by intraperitoneal injcetion of aristolochic acid[15 mg·(kg·d)^(-1)]for three consecutive days.HE and Masson were used to observe that pathological change of renal tissue.CD3,F4/80 and Ly6G were detected by immunohistochemistry to evaluate the infiltration of immun inflammatory cells in renal tissue,a-smooth muscle actin(SMA),fibroblast specific protein-1(FSP-1)and collagen type I al(coll al)were measured to evalue the renal fibrosis.Results Compared with the body weight of mice in ANN group was significantly lower than that in control group(P<0.05).Compared with the control group,the serum urea nitrogen and creatinine levels of ANN group were significantly increased(alLP<0.001).The renal tubule cells were swollen and vacuolated in F5d group,whereas,for the F15d group,the renal tubule cells atrophied,the lumen dilated and hyaline casts formed in the lumen.Both CD3 and F4/80 were not expressed in F5d group and significantly expressed in the F15d group.FSP-1 expression appeared in the F5d group and increased gradually.The expression of a-SMA was found in F15d group mice.No expression of coll al was found in F5d group and F15d group,No expression of the above indexes was found in the control group.Conclusions ANN mice model can well simulate the pathological development of A AN.The tubular intersitital injury that induced by immune inflammation exist in the mice model.In the pathological process,the renal interstitial fibrosis changes even earlier than the significant immune inflammatory cell infiltration,which may be related to the transformation of renal tubular epithelial cells into fibroblastes after injury.

关 键 词：肾炎 间质性 小鼠 模型 动物 马兜铃酸 

分 类 号：R692[医药卫生—泌尿科学] R-332[医药卫生—外科学]