浏览全部资源
扫码关注微信
氨基甲酰促红素对大鼠肾脏缺血再灌注损伤的保护作用
Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats
- 第三军医大学学报 2019年41卷第16期 页码：1545-1551
- 作者机构：
050051 石家庄，河北医科大学第三医院肾内科，河北省肾脏病研究中心
- 作者简介：
[ 李英，E-mail:liyinghebei@126.com LI Ying, E-mail:liyinghebei@126.com
- 基金信息：中华医学会肾脏病学分会青年研究与发展项目(13030410426)
DOI：10.16016/j.1000-5404.201903174
中图分类号： R364.12; R699.2; R977.9收稿：2019-03-21，
修回：2019-04-17，
纸质出版：2019-08-30
- 稿件说明：
移动端阅览
迟雁青, 张涛, 康英丽, 等. 氨基甲酰促红素对大鼠肾脏缺血再灌注损伤的保护作用[J]. 第三军医大学学报, 2019,41(16):1545-1551.
Yanqing CHI, Tao ZHANG, Yingli KANG, et al. Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats[J]. Journal of Third Military Medical University, 2019, 41(16): 1545-1551.
迟雁青, 张涛, 康英丽, 等. 氨基甲酰促红素对大鼠肾脏缺血再灌注损伤的保护作用[J]. 第三军医大学学报, 2019,41(16):1545-1551. DOI： 10.16016/j.1000-5404.201903174.
Yanqing CHI, Tao ZHANG, Yingli KANG, et al. Protective effect of carbamoylated erythropoietin against renal ischemia-reperfusion injury in rats[J]. Journal of Third Military Medical University, 2019, 41(16): 1545-1551. DOI： 10.16016/j.1000-5404.201903174.
摘要
目的
2
探讨氨基甲酰促红细胞生成素(carbamoyl-erythropoietin
CEPO)对大鼠肾脏及人肾小管上皮细胞(HK-2)缺血再灌注损伤的保护作用。
方法
2
构建SD大鼠肾脏缺血再灌注肾损伤模型，造模后0、24、48 h按照5 000 U/kg的剂量向腹腔内注射促红细胞生成素(EPO)或者CEPO，与肾脏缺血再灌注肾损伤模型组和假手术组进行对比分析，观察各组大鼠血清尿素氮(BUN)、血肌酐(Scr)、红细胞比容(Hct)，肾组织匀浆超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)，血清中IL-6、IL-10变化，肾组织PAS染色观察肾脏病理改变。对HK-2细胞进行缺血再灌注损伤处理，同时给予EPO和CEPO干预处理，实时定量RT-PCR检测IL-6、IL-10、TNF-α mRNA表达，Western blot检测IL-6、IL-10和凋亡相关蛋白cleaved-Caspase 3的蛋白表达。
结果
2
在大鼠肾脏缺血再灌注模型中，EPO或者CEPO干预治疗后，大鼠Scr、BUN水平明显降低；血清中促炎因子IL-6水平明显降低，抗炎因子IL-10水平明显提升；肾组织匀浆中MDA、TNF-α水平明显降低，SOD水平明显升高(
P
<
0.05)；PAS染色显示肾损伤明显减轻，且CEPO较EPO能起到更好的效果，CEPO治疗组Hct升高较EPO治疗组更加缓和(
P
<
0.
05)。HK-2细胞缺血再灌注模型中，EPO和CEPO能降低缺血再灌注HK-2细胞内TNF-α和IL-6 mRNA的表达，增加IL-10 mRNA和蛋白的表达，降低IL-6和cleaved-Caspase 3蛋白的表达，且CEPO能显示出更好的效果(
P
<
0.05)。
结论
2
CEPO可能通过减轻炎症和减少凋亡发挥缓解缺血再灌注对肾脏的损伤作用，并且相对EPO能减轻Hct升高的副作用。
Abstract
Objective
2
To investigate the protective effect of carbamoyl-erythropoietin (CEPO) against ischemia-reperfusion (IR) injury in rat kidneys and in human renal tubular epithelial cells (HK-2).
Methods
2
In a SD rat model of renal IR injury
EPO or CEPO was intraperitoneally injected at the dose of 5 000 U/kg at 0
24
and 48 h after renal IR. Serum levels of urea nitrogen (BUN) and creatinine (Scr)
hematocrit (Hct)
and the levels of superoxide dismutase (SOD)
malondialdehyde (MDA)
and tumor necrosis factor-α (TNF-α) in the kidney homogenate were detected; serum levels of interleukin-6 (IL-6) and IL-10 were detected and PAS staining was used for assessment of the renal pathologies. HK-2 cells were exposed to IR injury and treated with EPO or CEPO
and the mRNA expressions of IL-6
IL-10
and TNF-α were detected using Real-time PCR; the protein expressions of IL-6
IL-10
and cleaved Caspase-3 were analyzed with Western blotting.
Results
2
In the rat model of renal IR injury
Scr
BUN and IL-6 levels were reduced and serum IL-10 level was increased significantly after treatment with EPO or CEPO
which also significantly lowered the levels of MDA and TNF-α and increased SOD levels in the kidney homogenate (
P
<
0.05). PAS staining showed a significant improvement of renal pathological damages after the treatments
and the effect was more obvious with CEPO. CEPO treatment resulted in a milder increase in Hct as compared with EPO (
P
<
0.05). In HK-2 cells with IR injury
both EPO and CEPO treatment reduced the mRNA expressions of TNF-α and IL-6
increased the mRNA and p
rotein expressions of IL-10
and reduced the protein expressions of IL-10 and cleaved Caspase-3
and these effects were significantly more obvious with CEPO than with EPO treatment (
P
<
0.05).
Conclusion
2
CEPO can alleviate renal IR injury in rats by reducing inflammation and apoptosis
and can more effectively suppress the elevation of Hct than EPO in the rat models.
关键词
Keywords
references
KEZIĆ A, STAJIC N, THAISS F. Innate immune response in kidney Ischemia/Reperfusion injury: potential target for therapy[J]. J Immunol Res, 2017, 2017: 6305439. DOI: 10.1155/2017/6305439.
YASSIN M M, HARKIN D W, BARROS D'SA A A, et al . Lower limb ischemia-reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunction[J ] . World J Surg, 2002, 26(1): 115-121. DOI: 10.1007/s00268-001-0169-2.
BRINES M, GRASSO G, FIORDALISO F, et al . Erythropoietin mediates tissue protection through an erythropo ietin and common beta-subunitheteroreceptor[J ] . Proc Natl Acad Sci U S A, 2004, 101(41): 14907-14912. DOI: 10.1073/pnas.0406491101.
FRANCIS A, BAYNOSA R.Ischaemia-reperfusion injury and hyperbaric oxygen pathways: A review of cellular mechanisms[J]. Diving Hyperb Med, 2017, 47(2): 110-117.
XU Z, ZHAO K, HAN P, et al .Octreotide ameliorates renal Ischemia/Reperfusion injury via antioxidation and anti-inflammation[J ] . Transplant Proc, 2017, 49(8): 1916-1922. DOI: 10.1016/j.transproceed.2017.05.008..
REN C C, ZHU W, WANG Q W, et al . The renal protect function of erythropoietin after release of bilateral ureteral obstruction in a rat model[J ] . Clin Sci, 2018, 132(18): 2071-2085. DOI: 10.1042/CS20180178.
SHARPLES E J, YAQOOB M M. Erythropoietin and acute renal failure[J]. Semin Nephrol, 2006, 26(4): 325-331. DOI: 10.1016/j.semnephrol.2006.05.010.
ABE T, ISAKA Y, IMAMURA R, et al .Carbamylated erythropoietin ameliorates cyclosporine nephropathy without stimulating erythropoiesis[J ] . Cell Transplant, 2012, 21(2/3): 571-580. DOI: 10.3727/096368911X605501.
TÖGEL F E, AHLSTROM J D, YANG Y, et al . Carbamylated erythropoietin outperforms erythropoietin in the treatment of AKI-on-CKD and other AKI models[J ] . J Am Soc Nephrol, 2016, 27(11): 3394-3404. DOI: 10.1681/ASN.2015091059.
CASSIS P, AZZOLLINI N, SOLINI S, et al . Bothdarbepoetin alfa and carbamylated erythropoietin prevent kidney graft dysfunction due to ischemia/reperfusion in rats[J ] . Transplantation, 2011, 92(3): 271-279. DOI: 10.1097/TP.0b013e3182241106.
CERNARO V, SFACTERIA A, RIFICI C, et al .Renoprotective effect of erythropoietin in zebrafish after administration of gentamicin: An immunohistochemical study for β-catenin and c-kit expression[J ] . J Nephrol, 2017, 30(3): 385-391. DOI: 10.1007/s40620-016-0353-y.
MALEK M, NEMATBAKHSH M. Renal ischemia/reperfusion injury; from pathophysiology totreatment[J]. J Renal Inj Prev, 2015, 4(2): 20-27. DOI: 10.12861/jrip.2015.06.
ZHAO L S, XU L N, TAO X F, et al . Protective effect of the total flavonoids fromrosa laevigata michx fruit on renal ischemia-reperfusion injury through suppression of oxidative stres s and inflammation[J ] . Molecules, 2016, 21(7): E952. DOI: 10.3390/molecules21070952.
OLIVEIRA R C, BRITO M V, RIBEIRO R F Júnior, et al . Influence of remote ischemic conditioning and tramadol hydrochloride on oxidative stress inkidney ischemia/reperfusion injury in rats[J ] . Acta Cir Bras, 2017, 32(3): 229-235.DOI: 10.1590/S0102-865020170030000007.
GODET C, GOUJON J M, PETIT I, et al . Endotoxin tolerance enhances interleukin-10 renal expression and decreases ischemia-reperfusionrenal injury in rats[J ] . Shock, 2006, 25(4): 384-388.DOI: 10.1097/01.shk.0000209528.35743.54.
BANAEI S, AHMADIASL N, ALIHEMMATI A. Combination anti-apoptotic effect of erythropoietin and melatonin on ischemia reperfusion-induced renal injury in rats[J]. Acta Med Iran, 2016, 54(10): 624-630.
WICHAPOON B, PUNSAWAD C, VIRIYAVEJAKUL P. Expression of cleaved caspase-3 in renal tubular cells in plasmodium falciparum malaria patients[J]. Nephrology (Carlton), 2017, 22(1): 79-84. DOI: 10.1111/nep.12715.
TANG Z H, SUN X C, SHI Q H, et al . Beneficial effects of carbamylated erythropoietin against oxyg en-glucose deprivation/reperfusion-induced astrocyte swelling: proposed molecular mechanisms of action[J ] . Neurosci Lett, 2012, 530(1): 23-28. DOI: 10.1016/j.neulet.2012.09.029.
LI R, ZHANG L M, SUN W B. Erythropoietin rescues primary rat cortical neurons frompyroptosis and apoptosis via Erk1/2-Nrf2/Bach1 signal pathway[J ] . Brain Res Bull, 2017, 130: 236-244. DOI: 10.1016/j.brainresbull.2017.01.016.
ZOU Y R, ZHANG J, WANG J, et al . Erythropoietin receptor activation protects the kidney from Ischemia/Reperfusion-induced apoptosis by activating ERK/p53 signalpathway[J ] . Transplant Proc, 2016, 48(1): 217-221. DOI: 10.1016/j.transproceed.2016.01.009.
0
浏览量
0
下载量
0
CSCD
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 技术支持由北京北大方正电子有限公司提供 京ICP备09064830号-19
京公网安备11010802024621 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies
