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Establishment Of Animal Model Of AA And The Treatment Study Of Andi To AA Mouse

Posted on:2002-10-12Degree:MasterType:Thesis
Country:ChinaCandidate:J Y SunFull Text:PDF
GTID:2144360032452365Subject:Laboratory Animal Science
Abstract/Summary:PDF Full Text Request
Aplastic Anemia (AA) is one of common and intractable diseases in clinics, there are no special and effective methods for the treatment of AA until now, but two principles must be obeyed in clinics, one is blood transfusion therapy and the other is the combination of the traditional Chinese medecine and western medicine. The therapeutic effectiveness of the former has been proved, but it is restricted by blood source.Not the same as the former, the medicine,especially the traditional Chinese medicine has made obvious progress.The purpose of the experiments was firstly to establish a steady, simple, easily to be operated and high-successful-rate mouse model with pathogenesis and clinical characteristics similar to those of human AA, And then to evaluate the treatment of andi to mouse of AA and provide experiment data for clinical treatment. 1. Establishment of mouse model of AAMethods: Consulting model-making methods of references and predisposing factors of AA,by orthogonal exeperimental design,we tried to look for optimum combination of factors and levels.Finally, we selected the dosages as follows, the model of AA was formed by injection 50.0mg -kg-11 chloramphenicol and 62.5 mg -kg-1 cyclophosphamide for three days,on the fourth day after the irradiation with 3.0 Gy 60Co- Y rays. More studies (including peripheral hemogram and morphological examination) show : (1) the peripheral hemogram of model mouse minimize on the 7th day (p<0.01),and rise again to some extent and stay at a level, on 27th day ,3 blood components are significantly different from the control respectively (p<0.01), on the 35th day, almost all recovered to the normal level.(2) Bone marrow biopsy showed that hematopoietic cell capacity of model mouse was less than 20% on the 11th day, they had been replaced by lipocyte to a great extent ,and interstitial edema and blood sinusoid dilatation happened .From then on, hematopoietic cell increase gradually and on the 35th day, hematopoiesis cell capacity approximately accounted for 50%.(3)Morphological studies showed that splenic capsule of model mouse were not intact, red and white pulp have no obviously boundaries, splenic cords atrophied and immunoblast proliferated obviously, splenic sinusoid hyperemiaed greatly, tissue necrosissed partly, no splenic lymph nodules appeared, it had been found that a large number of splenic lymph nodules appeared and lymphocyte proliferated on the 27th day, splenic sinusoid hyperemia abated and red and white pulp have obvious boundaries. (4) On the 7th day,the ultrastructure of spleen of model mouse showed that lynphocyte decreased , necrosis increased , blood sinusoid dilated more and endothelial cell were damaged, nucleus dying deepen, chromatin condensed, nuclear membrane became oblivious. Then, it improved parallelly with pathological section ,on the 27th day , lymphocyte increased , partial cell division indicated.Conclusion: (1) This model hasthe following characteristics: easy to be operated and be carried out, reproducible, steady, pathological mechanism similar to clinical AA , lasting for over 30 days and easy to screen effective drugs to treat AA. 2. the treatment study of andi to AA mouseBy the examination of peripheral hemogram, bone marrow biopsy , pathological and eletron microscope (EM) section of spleen . Results: (1) By intraperitoneal injection ,the mouse of AA showed improvements in 3 blood components greatly(p<0.01).Bone marrow proliferated and restored to the normal level, hematopoietic cell increased obviously (hematopoietic cell capacity was more than 40%), and made atrophied spleen restored to normality.(2) The peripherial hemogram of the large and middle dosages of andi restored too, we hadn't found any damages on pathology section of internal organs of mouse at these dosages.The effectiveness of Andi is better than Tanozolol.?The weights of spleen and thymus of mouse increased significantly (p<0.01), the morphological examination and ultra-structure greatly improved after being given Andi.Conclusion: (1) The mode...
Keywords/Search Tags:andi, 60Co-γ ray, chloramphenicol, cyclophosphamide, anemia, aplastic, animal model, therapeutics, Tanozolol
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