Necrostatin-1对输尿管梗阻小鼠肾脏炎症的影响

发布时间：2019-06-13 15:52

【摘要】：目的探讨necroptosis(坏死性凋亡)抑制剂Necrostatin-1(Nec-1)对单侧输尿管梗阻(unilateral ureter obstruction,UUO)小鼠肾脏炎症的影响。方法雄性C57BL/6J小鼠随机分为假手术组(Sham组)、左侧输尿管结扎组(UUO组)、UUO+Nec-1治疗组(UN组),术后7天处死小鼠取左肾。收集血清测定肌酐(Scr)、尿素氮(BUN)水平;HE染色观察肾脏形态学改变;免疫组化法和Western blot法分别检测肾脏组织中坏死性凋亡相关指标RIP1、RIP3、MLKL以及炎症相关因子TNF-α、IL-1β、MCP-1的表达。结果与Sham组相比,UUO组小鼠RIP1、RIP3和MLKL蛋白表达明显升高,同时伴有TNF-α、IL-1β、MCP-1表达增多。Nec-1治疗显著降低了上述蛋白的表达水平,同时HE染色显示肾间质炎性反应和肾小管损伤程度有所减轻,Scr和BUN水平提示肾功能有所改善。结论 Nec-1通过抑制necroptosis减轻了单侧输尿管梗阻小鼠肾脏的炎症反应,这可能成为治疗肾脏继发炎症的新靶点。
[Abstract]:Objective to investigate the effect of necroptosis (Necrotic apoptosis) inhibitor Necrostatin-1 (Nec-1) on renal inflammation in mice with unilateral Ureteral obstruction (unilateral ureter obstruction,UUO). Methods male C57BL/6J mice were randomly divided into sham operation group (Sham group) and left ureter ligature group (UUO group), UUO Nec-1 treatment group (UN group). The mice were killed 7 days after operation to take the left kidney. The serum levels of (Scr), urea nitrogen (BUN) were measured, the morphological changes of kidney were observed by HE staining, and the expressions of RIP1,RIP3,MLKL and TNF- 伪, IL-1 尾, MCP-1 in renal tissue were detected by immunohistochemistry and Western blot, respectively. Results compared with Sham group, the expression of RIP1,RIP3 and MLKL protein in UUO group was significantly higher than that in UUO group, accompanied by the increase of TNF- 伪, IL-1 尾, MCP-1 expression. Nec-1 treatment significantly decreased the expression of these proteins. HE staining showed that the inflammatory reaction of kidney and the degree of tubular injury were alleviated, and the levels of Scr and BUN suggested that renal function was improved. Conclusion Nec-1 can reduce the inflammatory reaction of kidney in mice with unilateral ureter obstruction by inhibiting necroptosis, which may be a new target for the treatment of secondary inflammation of kidney.
【作者单位】：河北医科大学病理学教研室;河北医科大学第三医院肾内科;
【基金】：河北省首批青年拔尖人才项目(QNBJ16002) 河北省卫生厅重点科技研究计划(20150628) 河北省博士后科研资助项目(B2015003028)
【分类号】：R692

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