| Background and Objective:Many studies show that grade 3 or higher myelosuppression induced by concurrent radiochemotherapy in cervical cancer was 30-50%. As we all know,the radiation volume of pelvic bone marrow and chemotherapy were the most important factors for CRT induced bone marrow suppression.Whether cervical cancer resection the ovaries and estrogen deficiency was the important factor for myelosuppression was nuknow?More and more research shows that there is close relationship between estrogen and hematopoiesis, estrogen can promote bone marrow hematopoietic function and accelerate the proliferation of hematopoietic stem cells.It also can increases haematopoietic stem cell self-renewal in females rats. Studies have shown that when the lack of estrogen, it can be reduced in hematopoietic tissue and exhaustion hematopoietic function as time goes. In addition, more and more research has shown that estrogen have radioprotective effect.Both the nature estrogens like estradiol and the synthetic estrogens like diethylstilbestrol and phytoestrogens like genistein exerted radioprotective actions on radiation sickness of experimental animals including impeoving the survival and accelerating the recovery of hematopoiesis.Therefore, We speculate that estrogen deficiency may facilitate the impairment of haematopoiesis due to radiotherapy.In order to clear this hypothesis, oestrogen-deficiency model is established through bilateral ovaries excision, so that we investigated the potential influence of ovariectomy on radiation-induced myelosuppression.Materials and Methods:Female SD rats were randomly divided into 4 groups (6 rats each), and ovariectomized (OVX),sham ovariectomized (Sham) surgically under pentobarbital anaesthesia. The levels of serum estrogen were determined by chemiluminescence assay after 4 weeks. All rats were sacrificed at 7 days following whole-body irradiation with a single dose of 6 Gy, and the count of white blood cells (WBC), red blood cells (RBC), hemoglobin(Hb), platelet(PLT) of peripheral blood was tested. The levels of serum estrogen were determined again, the bone marrow cells (BMCs) were collected from the femur and tibia, and CD90+/CD45RC- hematopoietic stem cells (HSCs) was measured by FCM assay, and the hematopoietic activity of BMCs was evaluated using colony-forming units-granulocyte/macrophage (CFU-GM) assay.Results:We found that the estrogen level was significantly decreased in OVX (17.05±2.98 pg/ml) compared to Sham (53.40±7.02 pg/ml) (P<0.05) indicating that an estrogen-deficiency rat model was achieved by ovariectomy.After radiation, the estrogen level of irradiated Sham (40.72±5.14 pg/ml) compared to irradiated OVX(18.19 ±3.95 pg/ml) was significantly decreased(P<0.05). The number of WBC,PLT in peripheral blood, the volume of hemopoietic tissue in bone marrow,CD90+ /CD45RC- HSCs and CFU-GM in BMCs was significantly reduced in OVX+IR group rats (2.43±0.51×109/L,614.50±113.79×109/L,17.33±4,46%,1.04±0.22% and 115.5±21.2/1.5×104 cells, respectively), compared to Sham+IR group rats (3.32±0.45×109/L,752.83±96.98×1O9/L,24.5±4.04%,1.53±0.21% and 157.67±24.34/1.5×104 cells, respectively) (P<0.05), but showed no difference between non-irradiated OVX(7.10±1.08×109/L,1172.10±110.62×109/L,55.53± 6.47%,2.34±0.21%,323.67±19.13/1.5×104 cells, respectively) and Sham rats(6.76±1.14×109/L,1088.70±121.56×109/L,59.17±4.12%,2.51±0.19%, 309.17±27.75/1.5×104 cells, respectively) (P>0.05).Conclusions:The estrogen levels of rats with ovarian excision were significantly decreased after 4 weeks,and the estrogen deficiency model was succefully established.To maintain a certain level of estrogen can increased the bone marrow HSC numbers after radiotherapy,HSC CFU-GM formation ability,bone marrow hematopietic tissue volume and peripheral blood WBC and PLT counts and so on,the overall improvement of radiotherapy-induced bone marrow suppression. |
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