Effect Of Erythropoietin On GRP78 And CHOP In The Rat Rhabdomyolysis Induced Acute Kidnry Injury

Objective: Earthquakes, traffic accidents, high-intensity military training can cause rhabdomyolysis, and lead to acute kidney injury. When the body has rhabdomyolysis with acute renal injury, large amounts of myoglobins go into the blood, and block tubules. This can lead to apoptosis of renal tubular epithelial cells. Studies have found that the apoptosis of renal tubular epithelial cells is the main form of acute kidney injury. Endoplasmic reticulum road is a new cell apoptosis pathway that have discovered in recent years, and the core of the pathway is the endoplasmic reticulum stress(ERS). When the body is stimulated, the endoplasmic reticulum homeostasis is damaged, then the body activates the unfolded protein response(UPR)in the early ERS. The UPR will protect the cell damage caused by the ERS. Glucose-regulated protein 78(glucose regulated protein 78, GRP78) that is a network-centric UPR protein, plays a key role in the activation of the UPR process. Continued endoplasmic reticulum stress activates apoptosis signaling pathways [2], which lead to apoptosis of renal tubular epithelial cells, and the transcriptional activation of CHOP(CCAAT / enhancer binding protein homologous protein) plays a key role during this process. Studies have shown that erythropoietin(EPO) can promote the regeneration of tubular epithelial cells, and accelerate the recovery of renal function in the model of ischemia-reperfusion injury, rhabdomyolysis-induced acute kidney injury, cisplatin-induced acute kidney injury. In the model of rhabdomyolysis with acute renal injury, whether the protective effect of EPO on the kidney associated with GRP78 and CHOP, there is no study shows. To investigate the protection mechanism of EPO in habdomyolysis kidney injury, this study model glycerol-induced rhabdomyolysis with acute kidney injury were the following research. This study using glycerol rhabdomyolysis induced acute kidney injury model was carried out as follows.Method: Healthy male Sprague-Dawley(SD) rats were randomly divided into four groups: control group(CN,n=6), acute kidney injury group(AKI,n=18),AKI+EPO group(n=18), CN+EPO group(n=18),AKI group, AKI+EPO group and CN+EPO group is divided into three subgroupsbased onin jection time,1h,6h and 24 h groups of six rats. All animals were sacrificed on their each time. Blood samples and kidney tissues were collected. Semi automatic biochemical analyzer to detect the serum urea nitrogen, creatinine levels; The serum myoglobin were detected by ELISA method. Hematoxylin and eosin(he) staining to observe the renal pathological; The protein expression of GRP78 and CHOP was detected by immunohistochemistry.Result:(1)Compared with control group, significant increases in the levels of SCr, BUN and Mb were observed in AKI group(P<0.05,P<0.01). The level of plasma urea nitrogen, creatinine were reached the peak after the injection of glycerol 24h; The level of urea nitrogen in AKI group of EPO 6h was lower than that in the AKI group(P<0.05); Compared with the same period of AKI, the levels of 6h and 24 h in EPO AKI group were significantly lower than that in the same period(P< 0.05, P<0.01).(2) HE staining showed no significant changes in the renal tissue of control group; AKI group 1h, 6h and 24 h pathological damage gradually increased, and the damaged parts of concentrated in the kidney tubules; AKI+EPO group was reduced compared with the same period AKI group.(3)Immunohistochemical analysis showed that: compared with the control group, the expression of GRP78 protein in AKI group appeared in glycerol injection 1H(P<0.05). With the increased time of glycerol, the expression of GRP78 protein was increased, reached the peak at 24 h. Except the group of AKI+EPO1h, the GRP78 protein expression of AKI+EPO6h and AKI+EPO24h were reduced compared with AKI group(P<0.05).Compared with the same period in the control group, except AKI1 h group, the significant increases of CHOP protein expression were found in the AKI group 6h and 24h(P<0.01); Compared with the same period in the AKI group, except AKI+EPO1h group, the significant reduces of CHOP protein expression were found in the AKI+EPO group 6h and 24h(P<0.05).Conclusion: AKI activates UPR in renal tubular epithelial cells. EPO has a protective effect on the kidneys with rhabdomyolysis-induced acute kidney injury, which may be related to the regulation of UPR-induced apoptosis.