探讨STAT3抑制剂S3I－201对小鼠实验性肾小管间质纤维化的保护作用。

采用单侧输尿管梗阻手术的方法建立肾小管间质纤维化模型。将实验小鼠随机分为药物假手术组(Sham＋S3I－201)，安慰剂假手术组(Sham＋Vehicle)，药物造模组(UUO＋S3I－201)，安慰剂造模组(UUO＋Vehicle)4组，通过腹腔注射S3I－201溶液(药物)或0.05%DMSO PBS(安慰剂)给药，每天给药一次。造模第7天时留取肾脏标本，用Masson染色和颜色面积测算法评估胶原蛋白沉积的情况。用qRT－PCR法检测肾组织内趋化因子配体16(CXCL16)，白介素－1β(IL－1β)，细胞间黏附分子1(ICAM－1)，转化生长因子－β(TGF－β)，肿瘤坏死因子(TNF－α)的mRNA表达，用免疫组化法染色和免疫印迹法检测PDGFRβ蛋白在梗阻肾脏内的表达。

UUO＋Vehicle小鼠的肾间质胶原蛋白沉积显著高于Sham＋Vehicle组(P<0.05)。UUO＋Vehicle小鼠肾组织CXCL16，IL－1β，ICAM－1，TGF－β，TNF－α的mRNA表达显著高于Sham＋Vehicle组(P<0.05)，UUO＋Vehicle小鼠肾组织血小板来源生长因子受体β(PDGFRβ)蛋白表达显著高于Sham＋Vehicle组(P<0.05)。经过S3I－201治疗7 d后，UUO＋S3I－201小鼠的上述各项指标均显著低于UUO＋Vehicle(P<0.05)。

S3I－201通过抑制多种细胞因子的mRNA表达，以及降低PDGFRβ蛋白的表达，减轻实验性肾小管间质纤维化小鼠的肾间质炎症反应，从而发挥肾脏保护作用。

To investigate the protective effects of STAT3 inhibitor S3I-201 in experimental renal tubulointerstitial fibrosis of mice.

A model of renal tubulointerstitial fibrosis was established by the method of unilateral ureteral obstruction (UUO). The experimental mice were randomly divided into a drug-sham operation group (Sham+ S3I-201), a placebo-sham operation group (Sham+ Vehicle), a drug-model group (UUO+ S3I-201), and a placebo-model group (UUO+ Vehicle). The four groups were administered intraperitoneally with S3I-201 solution (drug) or 0.05% DMSO PBS (placebo), once daily. Kidney specimens were taken on the 7th day of modeling, and collagen deposition was assessed by Masson staining and color area measurement algorithm. The qRT-PCR method was used to detect the mRNA expression of chemokine C-X-C-motif ligand 16 (CXCL16), interleukin-1β (IL-1β), intercellular adhesion molecule-1 (ICAM-1), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α), while immunohistochemical staining and immunoblotting methods were used to detect the protein expression of platelet-derived growth factor receptor β (PDGFRβ) in the obstructed kidneys.

Renal interstitial collagen deposition was significantly higher in the placebo-model group (UUO+ Vehicle) than in the placebo-sham operation group (Sham+ Vehicle) (P<0.05). The mRNA expression of CXCL16, IL-1β, ICAM-1, TGF-β, and TNF-α were also significantly higher in the placebo-model group (UUO+ Vehicle) than in the placebo-sham operation group (Sham+ Vehicle) (P<0.05). The protein expression of PDGFRβ was significantly higher in the placebo-model group (UUO+ Vehicle) than in the placebo-sham operation group (Sham+ Vehicle) (P<0.05). After S3I-201 treatment for 7 days, the above indexes were significantly lower in the drug-model group (UUO+ S3I-201) than in placebo-model group (UUO+ Vehicle).

S3I-201 had a renal protective effect by inhibiting mRNA expression of various cytokines, decreasing protein expression of PDGFRβ, and reducing renal interstitial inflammation in mice with experimental tubulointerstitial fibrosis.