Effects of stromal derived factor-1 and CXC chemokine receptor-4 in rats with white matter damage treated with human umbilical cord mesenchymal stem cells / 中华围产医学杂志

ABSTRACT

Objective To investigate the effects and the migration mechanisms of stromal derived factor-1 (SDF-1) and CXC chemokine receptor-4 (CXCR-4) in rats with white matter damage treated with human umbilical cord mesenchymal stem cells (hUC-MSCs).Methods A total of 108 three-day old Sprague-Dawley rats were randomly divided into the experimental group,control group and sham group.The left common carotid artery was ligated and then exposed to hypoxia of 6％ O2 and 94％ N2 in rats in the experimental and control groups.Rats in sham group were neither ligation nor hypoxia.After 24 hours,rats in the experimental group were administered 0.5 ml hUC-MSCs (1 × 106/ml) intraperitoneally,and rats in control and sham groups were administered 0.5 ml saline by the same way.Immunohistochemistry and reverse transcription-polymerase chain reaction were used to determine the expression of SDF-1 and CXCR-4 protein and mRNA in 5-,7-and 14-day-old rats.Analysis of variance and the LSD test were used for statistical analysis of the data.Results HE staining showed that,in 14 day-old rats of the experimental group,bilateral cerebral ventricles were similar with no cellular edema or necrocytosis.In the sham group,bilateral cerebral ventricles were also normal.However,in the control group,ventriculomegaly,cellular degeneration and necrocytosis were observed on the left side.On the 5th,7th and 14th day,SDF-1 protein levels were 0.15±0.06,0.24±0.01 and 0.12±0.01,and CXCR-4 protein levels were 0.35±0.16,0.60±0.21 and 0.72±0.25,respectively,in the experimental group; SDF-1 protein levels were 0.13 ± 0.01,0.16± 0.01 and 0.08± 0.01,and CXCR-4 protein levels were 0.18 ± 0.04,0.17 ± 0.09 and 0.25 ± 0.06,respectively,in the control group,and all were higher than those in the sham group (SDF-1 protein levels were 0.03 ± 0.01,0.04± 0.01 and 0.02±0.01; and CXCR-4 protein levels were 0.04±0.02,0.05±0.03 and 0.05±0.03,respectively) (LSD test,all P＜0.05).SDF-1 protein increased to a peak on the 7th day and decreased on the 14th day in the experimental group,however,these values were both higher than those in the control group (LSD test,both P＜0.05).CXCR-4 protein increased on the 5th day and continued to increase up to the 14th day in the experimental group,and these values were higher than those in the control group at the three time points (LSD test,all P＜0.05).In 5-,7-and 14-day-old rats,SDF-1 mRNA levels were 3.52 ± 0.33,4.18± 0.28 and 2.60± 0.21,respectively,in the experimental group,which were higher than those in the control group (2.07± 0.34,3.73 ± 0.28 and 2.08± 0.15,respectively),and were even higher than those in the sham group (0.99±0.17,1.00±0.16 and 1.31 ±0.32,respectively) (LSD test,all P＜0.05).In the experimental group,SDF-1 mRNA levels reached a peak on the 7th day,and on the 14th day,it decreased to the level lower than that on the 5th day (LSD test,all P＜0.05).In the control group,SDF-1 mRNA levels also reached a peak in 7-day-old rats,but not in 14-day-old rats,which was similar to 5-day old rats (LSD test,9＞0.05).In 5-,7 and 14-day-old rats of the experimental group,CXCR-4 mRNA levels were 1.32±0.29,1.75±0.36 and 2.33±0.49,respectively,higher than those in the sham group (1.00±0.16,0.94±0.16 and 0.81±0.14,respectively) and the control group (0.97±0.14,0.97±0.15 and 1.07±0.25,respectively) (LSD test,all P＜0.05).In the experimental group,CXCR-4 mRNA levels were higher in 14-day-old rats than that in 5-and 7-day-old rats (LSD test,both P＜0.05).Conclusions SDF-1/CXCR-4 may play a vital role in the migration of hUC-MSCs homing to damaged brain.