莪术醇对梗阻性肾病大鼠IRE1调控TRAF2、XBP1抑制细胞凋亡的影响

张翠, 张思琪, 王丹枫, 张腾娇, 孙博

中国药学杂志 ›› 2018, Vol. 53 ›› Issue (18) : 1557-1563.

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中国药学杂志 ›› 2018, Vol. 53 ›› Issue (18) : 1557-1563. DOI: 10.11669/cpj.2018.18.006
论著

莪术醇对梗阻性肾病大鼠IRE1调控TRAF2、XBP1抑制细胞凋亡的影响

  • 张翠, 张思琪, 王丹枫, 张腾娇, 孙博
作者信息 +

Effect of Curcumol on the Apoptosis Inhibition of TRAF2 and XBP1 Controled by IRE1 in Rats with Obstructive Nephropathy

  • ZHANG Cui, ZHANG Si-qi, WANG Dan-feng, ZHANG Teng-jiao, SUN Bo
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摘要

目的 探讨莪术醇对梗阻性肾病大鼠肌醇必需酶1(inositol requiring enzymel 1,IRE1)调控肿瘤坏死因子受体相关因子2(tumor necrosis factor receptor-associated factor 2,TRAF2)、X-盒结合蛋白1 (X-box binding protein 1,XBP1)抑制细胞凋亡的影响。方法 建立单侧输尿管梗阻诱导大鼠肾间质纤维化动物模型,将大鼠随机分为假手术组、模型组、依那普利组、莪术醇高、中、低剂量组;术后14 d处死大鼠并采集血清检测血清肌酐(Scr)和血尿素氮(BUN)水平;采用HE染色观察肾脏的病理改变及评定肾小管损伤指数;Masson染色观察肾间质胶原沉积的面积;采用TUNEL法检测肾小管上皮细胞凋亡;采用Western blot免疫印迹法检测肾组织糖调节蛋白78(GRP78)、IRE1、p-IRE1、TRAF2、XBP1蛋白表达水平。结果 各治疗组与模型组比较,肾小管损伤指数,肾间质胶原分布相对面积,血清Scr和BUN水平及GRP78、IRE1、p-IRE1、TRAF2、XBP1,表达均有差异(P<0.05,P<0.01)。莪术醇高剂量组与依那普利组比较,Scr和BUN降低(P<0.05),肾小管间质损伤、肾间质胶原分布相对面积和肾小管上皮细胞凋亡降低(P<0.05),肾组织中GRP78、IRE1、p-IRE1、TRAF2、XBP1的表达降低(P<0.05)。结论 莪术醇能够通过抑制IRE1磷酸化介导下游TRAF2蛋白表达,干预IRE1-XBP1信号通路活化,阻止细胞凋亡,从而减缓肾间质纤维化的进程。

Abstract

OBJECTIVE To investigate the effect of curcumol on the apoptosis inhibition of TRAF2 and XBP1 controled by IRE1 in rats with obstructive nephropathy. METHODS Rats were randomly divided into sham control group, model control group and enalapril group as well as high, medium and low formononetin groups. Animal model of RIF was established by unilateral ureteral obstruction (UUO). The rats were sacrificed at 14 d after UUO, and blood samples were collected. Levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were examined. Renal tubular damage index was determined by H&E staining. The area of RIF was determined by Masson staining. Expressions of GRP78,IRE1,p-IRE1,TRAF2 and XBP1 in kidney were determined by Western blotting analysis. Apoptosis of tubular epithelial cells was detected by TUNEL assay. RESULTS Levels of Scr and BUN, tubulointerstitial injury index, RIF and apoptotic index as well as expressions of GRP78,IRE1,p-IRE1,TRAF2 and XBP1 were different between the model control and treatment groups (P<0.05, P<0.01). Compared with the enalapril group, tubulointerstitial injury index and RIF as well as the levels of Scr and BUN were decreased (P < 0.05) in the high curcumol group. CONCLUSION The curcumol can block the apoptosis of renal tubular epithelial cells through interfering IRE1-XBP1 signaling pathway by inhibiting TRAF2 protein expression mediated by IRE1 phosphorylation. Ultimately, development of RIF was postponed.

关键词

莪术醇 / 单侧输尿管梗阻 / 肌醇必需酶1 / 肿瘤坏死因子受体相关因子2 / X-盒结合蛋白1

Key words

curcumol / unilateral ureteral obstruction / IRE1 / TRAF2 / XBP1

引用本文

导出引用
张翠, 张思琪, 王丹枫, 张腾娇, 孙博. 莪术醇对梗阻性肾病大鼠IRE1调控TRAF2、XBP1抑制细胞凋亡的影响[J]. 中国药学杂志, 2018, 53(18): 1557-1563 https://doi.org/10.11669/cpj.2018.18.006
ZHANG Cui, ZHANG Si-qi, WANG Dan-feng, ZHANG Teng-jiao, SUN Bo. Effect of Curcumol on the Apoptosis Inhibition of TRAF2 and XBP1 Controled by IRE1 in Rats with Obstructive Nephropathy[J]. Chinese Pharmaceutical Journal, 2018, 53(18): 1557-1563 https://doi.org/10.11669/cpj.2018.18.006
中图分类号: R965   

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基金

国家自然科学基金项目资助(81373547);哈尔滨商业大学研究团队支持项目资助(2016TD008);哈尔滨商业大学研究生创新科研项目资助(YJSCX2017-445HSD)
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