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The Thrombopoietic Effect Of Recombinant Thrombopoietin On Myelosuppressed Mice

Posted on:2003-07-02Degree:MasterType:Thesis
Country:ChinaCandidate:L J ZhangFull Text:PDF
GTID:2144360092496142Subject:Internal Medicine
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ObjectsSome experiments are carried out to study the stimulating effects of recombinant human thrombopoietin(rhTPO) to peripheral thrombo-poiesis and megakaryolytopoiesis of myelosuppressed mice after radiotherapy and chemotherapy. At the same time, comparing the therapeutic effects by various treat ways in order to determine the best mediation way.MethodsIn the experiments on animals, Balb/c mice were irradiated with 3. 5Gy total -body irradiation and dosed with 1. 2mg carboplatin, resulting in myelosuppressive thrombocytopenia model. The time was divided into 4 groups. One group is mediated previous to and following the radioactive chemotherapy. Another two are mediated before or after the radioactive and chemotherapy respectively. Moreover, a control group is set up. The index to observe: ①the minimal platelet count ②the duration of thromopenia( PLT <30% normal value) ③the time for platelet recovery (PLT ≥50% normal value) ④megakaryocyte counting per mm in pathology of sternal marrow in mice, and comparing the variation among different groups.Result①Fluctuation of platelet count after medication. In the pre/post and pre - group, platelet counts were increased on day 3 after treated with hTPO and reached a peak between days 6 and 7, increased by a-bout 3 -4 folds. However, as the ccontrol group is considered, the platelet counts were reduced to 10. 5% of initial value on day 9 and lasted for about a week at this level, and recovered on day 23. The results of 3 rhTPO treatment group and control group are shown as . PLT ( ×109/L)nadiris223 ±42,146 ±28,217 ±30,77 ±13(dayp< 0.001,u control) . The days of 3 rhTPO treatment group to recovery of normal PLT reduced. ②Megakaryocyte counting in pathogical specimen of mice sternum was examined on day 9 and 15. In the pre and pre - post group, the megakaryocytes were increased significantly on day 9 compared with control group ( p <0. 001) . And the megakaryo-cyte count in marrow tends to increase obviously on15.DiscussionMyelosuppression is a common side - effect of radiotherapy and chemotherapy, which may lead to severe thrombopenia and bleeding, resulting in the limitation of dose in the therapy mentioned above. Therefore, the effects on some radiactive - chemotherapic - sensive tumors are influenced to great extent. TPO was described for the first time in 1958. And in 1994, TPO was cloned and purified successfully. TPO is a kind of glycoprotein consisting of 332 amino acid, the ligand of oncogen c - MPL receptor, which is produced mainly in kid-ney and liver. Its major biological activity that was found at early stage is stimulation of megakaryocytopoiesis and thrombopoiesis. As a haematopoietic growth factor, TPO acts in a relatively lineage - specific manner in normal animal. To myelosuppressed mice, treatment with TPO will accelerate the recovery of PLT as well as RBC and neutro-phils. After the myelosuppressed mice model was prepared, three different mediations were selected in order to observe its stimulation effect to PLT and megakaryocyte. After exposed to radioactive chemotherapy, PLT and megakaryocyte of the mice in control group decreased rapidly, which reached 10. 4% and 9. 5% of pretreatment count respectively on day 9 and 11. This is just a reversible myelosuppressed model, the time required for 50% recovery of the baseline PLT and WBC count were 22d and 19. 3d respectively. Meanwhile, the megakaryocytes were also decreased obviously. In contrast to control group, rhTPO groups appear to possess the property of increasing PLT. Pre - group is similar to preventive medication, the tendency for PLT decreasing can not be avoided after radioactive - chemotherapy, although the medication for 5 days in advance has increased PLT counts by 3 folds. However, there is still difference between them. Meanwhile, post - group and pre/post group appear to be obviously different from comparing group. In addition, among the 3 treatment group, the result of post - group shows the longest duration and the shortest recov...
Keywords/Search Tags:rhTPO, myelosuppression, thrombopoiesis
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