Effect of mobilization bone marrow stem cells on hypoxia inducible factor-1a and epidermal growth factor in rats with renal injury induced by ischemic reperfusion / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate the mobilization of granulocyte-colony stimulating factor(G-CSF) with stem cell factor(SCF) in bone marrow stem cells(BMSC),and to observe the therapeutic effects of BMSC mobilization on repairing ischemia/reperfusion(I/R) renal injury induced by hypoxia inducible factor-1α (HIF-1α) and epidermal growth factor(EGF),and to investigate the mechanism for BMSC mobilization for repairing I/R renal injury.MethodsOne hundred and sixty male Sprague-Dawley rats(age:8-10 weeks) were randomly allocated into 4 groups(40 rats in each group):control group (group A),I/R group(group B),SCF + G-CSF treatment group (group C) and SCF + G-CSF control group(group D).The expressions of CD34 + and EGF were measured by immunohistochemistry technique,and the expression of EGF mRNA was measured by reverse transcriptase-polymerase chain reaction.Results 1.After I/R injury,the renal tubular epithelial cells were in a state of degeneration,necrosis,even exfoliation.As the time prolonged,the necrotic renal tubules were repaired gradually,but the repair in group C was not good compared with that in group B.The level of group C was obviously lower than that of group B on the 5th,10th,17th and 24th day(P ＜ 0.05).2.There was no significant difference in the percentage of CD34 + cells between group A and D(P ＞ 0.05).On 5 d postoperative,the level of CD34 + cells of group B and group C was conspicuous higher than group A and D (P ＜ 0.05),and that of group C was conspicuous higher than that of group B (P ＜ 0.05).They descended gradually from the 5 th day with the time prolonged.3.The expressions of HIF-1c of group B and group C had a highly positive reaction on the 5th day postoperatively and the level of HIF-1α of group B and group C decended to the normal level with the time prolonged,and at each time,the expression of HIF-1α of group C was significantly higher than that of other groups (P ＜ 0.05).4.On the 5th day postoperative,the expression of EGF of group B and group C showed a higher positive reaction on the 5th day postoperatively and the level of EGF in group B and group C descended to the normal level with the time prolonged,and at each time the expression of EGF of group C was significantly higher than that of the other groups (P ＜0.05).5.The expressions of EGF mRNA of group B and C showed higher positive reaction on the 5th day postoperatively(P ＜ 0.05).The level of EGF mRNA of group B was higher significantly than that of group A on the 17th day postoperatively(P ＜ 0.05).The level of EGF mRNA of group C was a peak and higher than that of other groups on the 10th day postoperatively(P ＜ 0.05).The level of EGF of group B and group C descended to a normal level with the time prolonged.6.There was a positive correlation between the expressions of HIF-1α and EGF (r =0.815,P ＜ 0.01).Conclusions Combination of SCF with the mobilization of G-CSF sufficiently homed BMSC to injured renal tissue was an important factor for the recovery of injured renal tubules.Combination of SCF with G-CSF may promote the expression of HIF-lα and EGF in the kidney may be one of the mechanisms of why combination of SCF with G-CSF can promote recovery from renal ischemic reperfusion injury.