Objective To explore the serum level of vascular endothelial growth factor (VEGF) of the patients with asymptomatic and symptomatic peripheral artery disease (PAD) in diabetics for providing evidence for screening the patients with PAD early. Methods Selected the study population including diabetics without PAD(90 cases),diabetics with asymptomatic PAD patients(93 cases)and diabetics with symptomatic PAD patients(92 cases). The level of serum VEGF was measured using enzyme linked immunosorbent assay(ELISA) and analyzed in the three groups. The varia-tion of serum VEGF was further analyzed in the three groups excluding the diabetic retinopathy in the stratified analysis. Results The serum level of VEGF with asymptomatic and symptomatic PAD in diabetics were increased,compared with the diabetics without PAD (P<0.05). Excluding the patients with diabetic retinopathy, the serum level of VEGF of the patients with asymptomatic and symptomatic PAD in diabet ics was still increased, compared with the dia betics without PAD (P<0.05). The serum level of VEGF level was significantly positively associated with HbA1c in the pa-tients with asymptomatic and symptomatic PAD in diabetics (r=0.267, 0.352, P all<0.05). Conclusion The level of serum VEGF in the patients with asymptomatic and symptomatic PAD in diabetics had been significantly increased.

BACKGROUNDBone marrow hematopoietic function suppression is one of the most common side effects of chemotherapy. After chemotherapy, the bone marrow structure gets destroyed and the cells died, which might cause the hematopoietic function suppression. Heme oxygenase-1 (HO-1) is a key enzyme of antioxidative metabolism that associates with cell proliferation and resistance to apoptosis. The aim of this study was to restore or resist the bone marrow from the damage of chemotherapy by the HO-1 expression of mouse mesenchymal stem cells (mMSCs) homing to the mice which had the chemotherapy-induced bone marrow suppression.

METHODSOne hundred and sixty female Balb/c mice (6-8-weeks old) were randomly divided into four groups. Each group was performed in 40 mice. The control group was intraperitoneally injected for 5 days and tail intravenously injected on the 6th day with normal saline. The chemotherapy-induced bone marrow suppression was established by intraperitoneally injecting cyclophosphamide (CTX) into the mice which performed as the chemotherapy group. The mMSCs were tail intravenously injected into 40 chemotherapically damaged mice which served as the mMSCs group. The difference between the HO-1 group and the mMSCs group was the injected cells. The HO-1 group was tail intravenously injected into the mMSCs that highly expressed HO-1 which was stimulated by hemin. The expression of HO-1 was analyzed by Western blotting and RT-PCR. Cell proliferation was measured using the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Histopathologic examinations were performed 1 week after injection.

RESULTSCompared with the control group, the expression levels of HO-1 mRNA and protein were significantly higher in the HO-1 group (all P < 0.05), even obviously than the mMSCs group. CTX treatment induced apoptosis and inhibited proliferation. After injected, the white blood cell (WBC), red blood cell (RBC) and platelet (PLT) declined fast and down to the bottom at the 7th day. The bone marrow structure was destroyed incomplete. In vitro, the survival rate of cells in chemotherapy group was less than 50% after 24 hours. In contrast, mMSCs could do a favor to the cellular cleavage and proliferation. They slowed down the cell mortality and more than 50% cells survived after 24 hours. The effects of blocking apoptosis and bone marrow recovery could be more effective in the HO-1 group. In the HO-1 group, it had observed that the bone marrow structure became complete and the hemogram closed to normal at 7th day.

CONCLUSIONSHO-1 played an important role in promoting the recovery of CTX-induced hematopoietic damage. We suggest that HO-1 is able to restore the functions of chemotherapy-induced hematopoietic damage.

Animals ; Apoptosis ; drug effects ; Blood Platelets ; drug effects ; Blotting, Western ; Bone Marrow ; drug effects ; enzymology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cyclophosphamide ; toxicity ; Erythrocytes ; drug effects ; Female ; Heme Oxygenase-1 ; genetics ; metabolism ; Leukocytes ; drug effects ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; enzymology ; physiology ; Mice ; Mice, Inbred BALB C ; Reverse Transcriptase Polymerase Chain Reaction