摘要
目的观察缺血再灌注(ischemia reperfusion,I/R)大鼠肾损伤模型中肾组织及尿液诱骗受体2(decoy receptor 2,DcR2)的表达变化,探讨其与肾损伤的关系。方法健康雄性SD大鼠40只,使用完全随机方法分为假手术组和I/R 60 min组,分别于术后1、3、7、21、35 d收集血、尿及双侧肾组织。检测各组大鼠血肌酐(serum creatinine,Scr)及尿NAG水平,使用PAS染色、Masson染色观察肾组织形态学变化并予以病理损伤评分,免疫组化检测肾组织DcR2表达,酶联免疫吸附法(ELISA)检测尿DcR2水平。结果与假手术组Scr(21.3±1.6)μmol/L、尿NAG(4.4±0.6)U/mmol相比,I/R 60 min组1、3、7、21、35 d时Scr[(122.2±15.4)、(193.5±27.7)、(66.4±10.2)、(37.8±6.2)、(34.4±2.8)μmol/L]显著升高(P<0.05),尿NAG[(9.8±2.0)、(17.0±2.5)、(7.8±1.5)、(6.5±2.1)、(6.7±2.3)U/mmol]显著升高(P<0.05);病理结果显示皮髓交界区域出现明显的肾小管细胞坏死、脱落、基底膜裸露、细胞管型形成等病理表现,并于再灌注后期出现肾小管萎缩、间质纤维化等慢性化表现;I/R60 min组肾组织DcR2表达及尿DcR2水平较假手术组显著升高(P<0.05),DcR2表达量及尿DcR2水平与肾功能、肾组织损伤程度呈正相关(P<0.05);DcR2表达量与肾间质纤维化程度呈正相关(P<0.05)。结论缺血再灌注大鼠肾组织DcR2表达量及尿DcR2水平与肾功能及肾组织损伤程度密切相关,DcR2可能在缺血再灌注后肾间质纤维化的进展中具有重要作用。
Objective To observe the expression of decoy receptor 2（ DcR2） in renal tissue and urine of rat after ischemia reperfusion injury（ I / R） for investigating its correlation to kidney injury. Methods Forty healthy male SD rats were randomized into sham operation group and I / R 60 min group. Blood,urine and bilateral renal tissues were collected at days 1,3,7,21 and 35 after operation. The levels of serum creatinine（ Scr） and urinary NAG（ u NAG） were detected by biochemical analysis. Renal morphologic changes were observed and pathologically assessed by PAS and Masson＇s trichrome staining. The expression of DcR2 in renal tissues was detected by immunohistochemical assay, and the expression of urine DcR2（ u DcR2） was measured by enzyme-linked immunosorbent assay（ ELISA）. Results Compared to the Scr and u NAG levels in the sham group（ 21. 3 ± 1. 6 and 4. 4 ± 0. 6 U / mmol,respectively）,they significantly increased in the I / R 60 min group（ P〈0. 05）. At days 1,3,7,21 and 35 post operation,the Scr levels were 122. 2 ± 15. 4,193. 5 ± 27. 7,66. 4 ± 10. 2,37. 8 ± 6. 2,and 34. 4 ± 2. 8 μmol / L,respectively.Accordingly,the u NAG levels were 9. 8 ± 2. 0,17. 0 ± 2. 5,7. 8 ± 1. 5,6. 5 ± 2. 1,6. 7 ± 2. 3 U / mmol,respectively. Obvious pathological changes were found at the corticomedullary junction in the I / R 60 min group,including acute tubular necrosis,denudation,brush border and formation of cellular casts,which progressed to renal tubule atrophy,interstitial fibrosis and chronic kidney disease in later stage of reperfusion.Additionally,the expression of DcR2 in renal tissue and urine was increased significantly in the I / R 60 min group compared to the sham group（ P〈0. 05）. The increased level of DcR2 and u DcR2 were positively correlated with renal function and kidney injury score（ P〈0. 05）. Meanwhile,the Masson staining showed that in the I / R 60 min group renal DcR2 expression was positively correlated with interstitial fibrosis（ P〈0. 05）. Conclusion The expression of DcR2 in renal tissue and u DcR2 level are positively related to renal function and kidney injury score in rats with I / R injury. This may suggest the important role of DcR2 played in the progress of renal interstitial fibrosis after ischemia reperfusion.
作者
刘佳睿
陈佳
陈客宏
林利容
张建国
李开龙
郑卢权
何娅妮
Liu Jiarui Chen Jia Chen Kehong Lin Lirong Zhang Jianguo Li Kailong Zheng Luquan He Yani(Department of Nephrology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, Chin)
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2017年第4期342-348,共7页
Journal of Third Military Medical University
基金
国家自然科学基金面上项目(8164792)~~
关键词
缺血再灌注损伤
急性肾损伤
DcR2
ischemia reperfusion injury
acute kidney injury
decoy receptor 2
