Font Size: a A A

Renal Effects Of Heme Oxygenase-1 Level After Reperfusion Injury Erythropoietin On Renal Ischemia

Posted on:2010-01-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:W WanFull Text:PDF
GTID:1264330401456084Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
BackgroudAcute kidney injury (AKI) is a clinical syndrome of primary and secondary renal dysfunction that often appears clinically, as for acute renal insufficiency (ARI) or acute renal failure (ARF), it is a replacement and extension. Researches have showed that the percentage of patients suffered from AKI among inpatients is10%. Erythropoietin (EPO) has been used for renal and cancer-related anemia for many years. It has been found that except for hematogenesis EPO can provide various protective effects for many organs and it is a therapeutic method for AKI. The mechanism of action of EPO is very complicated, it is not clear yet and needs further investigation.ObjectiveTo investigate the protective effect and mechanism of erythropoietin on renal ischemic reperfusion injury.MethodsEighty male SD rats weighed300to400g were randomly assigned to four groups: sham-operated group+Normal Saline (sham+NS), sham-operated+EPO group (sham+EPO), Ischemia Reperfusion+Normal Saline group (IR+NS), Ischemia Reperfusion+EPO group (IR+EPO). Duplicate the model of renal ischemic reperfusion:bilateral kidneys underwent90min ischemia by clamping renal pedicles, and then were reperfused for1,3,6,24and48h. A single dose of EPO was injected intraperitoneally5000IU/kg2h prior to occlusion. Animals were sacrificed at each reperfusion time point to obtain kidney and venous blood samples. The serum concentration of Cr and BUN were measured. Oxidative stress was evaluated according to semi-quantitive analysis of tissue HO-1and p-ERK expression by immunohistochemistry method.Results(1)There is no significant difference between two sham-operated groups, serum Cr and BUN (indicator of renal function) increased significantly in I/R group (p<0.05).The EPO pretreated animals exhibited improved renal function (no significance, p>0.05) compared with I/R group.(2) Immunohistochemistry analysis revealed that at1h of I/R, there is no significant difference of HO-1expression between four groups, and ischemia/reperfusion insult markedly increased HO-1expression (p<0.05) after1h of I/R. The indicator exhibited unimodal distribution with peak at24h. HO-1was increased more in IR+EPO group than IR+NS group with statistical significance at6h and24h of I/R.(3) Two operated groups exhibited improved p-ERK expression (p<0.05) compared with sham-operated group and it peaked at24h of I/R, but p-ERK at6h was close to that at24h. It was upregulated in EPO+IR group with statistical significance at3h and6h compared with NS+IR group.ConclusionsUnder ischemic reperfusion condition, the renal function is impaired, and the expression of HO-1and p-ERK are upregulated, pretreatment with EPO appears to increase HO-1and p-ERK more. The tendency that EPO downregulate SCr and BUN after renal ischemic reperfusion may be partly related with HO-1upregulation.
Keywords/Search Tags:Renal ischemic reperfusion injury, Oxidative stress, Erythropoietin, Phosphorylatedextracellular signal-regulated protein kinase, Heme oxygenase-1
PDF Full Text Request
Related items