Received:06 December 2016,
Published:30 April 2017
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Fengju Li, Changhong Du, Ke Yang, et al. Norepinephrine injection before ionizing radiation attenuates thrombopoiesis in mice[J]. Journal of Third Military Medical University, 2017, 39(8): 724-730.
Fengju Li, Changhong Du, Ke Yang, et al. Norepinephrine injection before ionizing radiation attenuates thrombopoiesis in mice[J]. Journal of Third Military Medical University, 2017, 39(8): 724-730. DOI: 10.16016/j.1000-5404.201612034.
Objective
2
To study the effect of norepinephrine (NE) on ionizing radiation (IR)-induced thrombocytopenia in mice and its possible mechanism.
Methods
2
Eighty normal C57BL/6 mice (8~10 weeks old) were randomly allocated into 4 equal groups and subjected to intraperitoneal injection of PBS or NE with or without total body irradiation (TBI) at 6 Gy for 24 h after the injection. At different time points following TBI
blood samples were collected from the tail vein of the mice for measuring platelet count and other routine blood biochemical parameters. The changes of the bone marrow cellularity were examined with HE staining at 9 d after TBI
and the changes in apoptosis of MO7e cells
cell cycle of megakaryocytic progenitors
and the frequency of LSK cells in mouse-derived Sca1
+
cells and in mice exposed to IR were analyzed with flow cytometry.
Results
2
As compared with those in PBS group
the platelet count in 3~10 d after injection and the frequency of HSCs of Lineage cells in murine bone marrow increased significantly [(1.44±0.08)%
vs
(1.05±0.10)%
P
<
0.05
]
. In addition
NE treatment significantly promoted the proliferation of HSCs
in vitro
which showed a dose response relationship (≤100 nmol/mL concentration). Further more
HE staining showed that the numbers of bone marrow nucleated cells and megakaryocytes were significantly higher in NE group than those in PBS group. Moreover
(12.10±3.12)% of G
0
/G
1
phase cells in the progenitor cells significantly decreased and (8.78±1.05)% of S phase cells in the progenitor cells significantly increased in NE group (
P
<
0.05). Effects were opposite when mice or cells were subje
cted to TBI after NE administration:the platelet count during the 7th~25th days and the number of bone marrow nucleated cells (
P
<
0.05)
the frequency of HSCs of Lineage-cells in murine bone marrow [(0.07±0.01)%
vs
(0.27±0.03)%
P
<
0.05
]
and the number of bone marrow nucleated cells and megakaryocytes in NE+IR group were significantly lower than those in PBS+IR group. Besides
the apoptostic rate of megakaryocytic progenitors in NE+IR group was significantly higher than the rate of in PBS+IR group[ (84.46±5.09)%
vs
(54.18±3.18)%
P
<
0.05
]
.
Conclusion
2
NE may aggravate acute radiation injury by unduly promoting proliferation of HSCs and megakaryocytic progenitors in mice.
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