α-平滑肌肌动蛋白及转化生长因子-β1在高尿酸血症大鼠肾小管间质纤维化中的表达

摘要

Objective To observe the expression of α-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-β1)in hyperuricemia rats with tubulointerstitial and to explore the possible mechanism of renal pro-fibrotic with these two factors. Methods 36 male SD rats were randomly divided into three groups:control group(Con),model group and Febuxostat group,with 12 rats in each group. 0.5% sodium carboxymethy cellulose(CMC)solution containing oteracil potassium (OP) was used to establish hyperuricemia model by gastric gavage once per-day.Therapy group was treated with Febuxostat at the same time. Con group was treated with 0.5% CMC only. Serum uric acid (SUA), creatinine (Scr),urea nitrogen (BUN)and 24-hour urinary protein excretion were measured at 0th ,4th and 8th week. 4 rats were sacrificed randomly at three times in each group.The histological changes of kidneys were observed via HE staining and Masson staining by light microscopy.The expression of TGF-β1 andα-SMA were examined with immunohistochemistry staining. Results Compared with Con group,the value of serum SUA,Scr,BUN in model group were higher at 4th week(P<0.05),and the expression of TGF-β1 andα-SMA were increased significantly(P<0.01).The renal interstitium injury was seen in model group at the same time,and became aggravation with the progression of the experiment. Febuxostat group has less renal damage versus model group. Conclusion High expression of TGF-β1 andα-SMA induced by hyperuricemia may enhance the development of tubulointerstitial fibrosis.%目的：观察α-平滑肌肌动蛋白（α-SMA）及转化生长因子-β1（TGF-β1）在高尿酸血症（HUA）大鼠肾小管间质纤维化（RIF）过程中的表达及意义。方法 SD 大鼠36只，随机分为对照组（Con）、模型组及非布司他组，每组12只。氧嗪酸钾（OP）溶于0．5％的羧甲基纤维素钠（CMC）溶液，模型组和非布司他组用 OP 灌胃，1次／d，制备 HUA 模型，非布司他组另予非布司他灌胃，Con 组仅予等量0．5％CMC 灌胃。于0、4、8周后检测血尿酸（SUA）、血肌酐（Scr）及 BUN，收集24 h 尿量，检测24 h 尿蛋白定量。第0、4、8周末每组随机处死4只大鼠，HE 染色及 Masson 染色观察肾组织病理变化，免疫组织化学法检测α-SMA、TGF-β1的表达。结果实验4周后，与 Con 组比较，模型组 SUA、Scr、BUN 升高（P＜0．05或 P＜0．01），TGF-β1、α-SMA 表达量增多（P ＜0．01），肾小管间质发生纤维化。实验8周后， RIF 加重；非布司他组 RIF 较模型组减轻（P ＜0．01）。结论 HUA 诱导肾组织 TGF-β1、α-SMA 表达量增加；α-SMA 及 TGF-β1表达增多促进 RIF 发生。