目的 · 探讨胰岛素样因子6(Insl6)对单侧输尿管梗阻(UUO)小鼠肾脏纤维化和钙化的影响。方法 · SPF 级 C57BL/6 雄 性小鼠24 只,随机分为3 组,假手术组(n=8)、 UUO+ 生理盐水组(n=8)和UUO+Insl6 组(n=8)。 UUO 模型建立后第10 日处死 小鼠,取术侧肾组织。采用天狼星红染色、Masson 染色、茜素红 S 染色分别检测肾脏胶原沉积及钙化程度,Western blotting 检测肾 脏 TGF-β1 表达,realtime-PCR 检测肾脏TGF-β1、BMP2、Col1a1、Col2a1 mRNA 表达。结果 · 与假手术组相比,UUO+ 生理盐水 组肾脏胶原面积百分比显著增加,以Ⅰ型胶原为主,钙盐沉积,TGF-β1 蛋白表达,TGF-β1、BMP2、Col1a1、Col2a1 mRNA 表达均 显著增加(均P<0.05)。与 UUO+ 生理盐水组相比,UUO+Insl6 组小鼠肾脏胶原面积,钙盐沉积,TGF-β1 蛋白,TGF-β1、BMP2、 Col1a1、Col2a1 mRNA 表达均显著降低(均P<0.05)。 结论 · Insl6 具有抗UUO 诱导的肾脏纤维化及钙化作用,其机制可能与调控 TGF-β1、collagen Ⅰ、BMP2、collagen Ⅱ表达水平有关。
高磊
,
吴世勇
,
蒋丹
,
王颖
,
李勇湧
,
王德伟
,
常广磊
,
张鹏
,
覃铮
,
张冬颖
. 胰岛素样因子6对单侧输尿管梗阻小鼠肾脏纤维化和钙化的影响[J]. 上海交通大学学报(医学版), 2017
, 37(12)
: 1616
.
DOI: 10.3969/j.issn.1674-8115.2017.12.006
Objective · To investigate the effects of insulin-like peptide 6 (Insl6) on renal fibrosis and calcification in unilateral ureteral obstruction (UUO) mice. Methods · Twenty-four SPF male mice with genotypic background of C57BL/6 were divided into Sham (n=8), UUO+saline (n=8) and UUO+Insl6 (n=8) groups randomly. Mice were sacrificed 10 days after operation and renal tissues of surgical side were obtained. Sirus red staining, Masson staining and alizarin red S staining were used to verify the level of collagen and calcium deposition. TGF-β1 expression was determined by Western blotting. Realtime-PCR was used for determining TGF-β1, BMP2, Col1a1, and Col2a1 mRNA expression. Results · Compared with sham group, fibrotic area especially collagen Ⅰ, calcium deposition, TGF-β1 protein, and TGF-β1, BMP2, Col1a1, and Col2a1 mRNA expression in UUO+saline group significantly
increased (all P<0.05). As compared with UUO+saline group, fibrotic area especially collagen Ⅰ, calcium deposition, TGF-β1 protein, and TGF-β1,
BMP2, Col1a1, and Col2a1 mRNA expression in UUO+Insl6 group significantly decreased (all P<0.05). Conclusion · Insl6 inhibits UUO-induced renal fibrosis and calcification, which may be related to regulation of TGF-β1, collagen Ⅰ , BMP2 and collagen Ⅱ expression levels.