Uterine leiomyomas are the common disease in women, and the incidence of the disease has a increasing tendency year after year. At least 25% reproductive women demonstrate clinically significant symptoms, and the incidence is as high as 77% histologically estimating from autopsy specimens.The exact pathogenesises of uterine leiomyomas are poorly understood. Many factors participate in the growth of leiomyomas, and the suppression of apoptosis is one of the most important factors, and in many apopotis- controlled genes,bcl-2 and bax are the most relative genes with the suppression of apoptosis in uterine leiomyomas.The tumor cell biology indicate: the suppression of apoptosis is important to the production and growth of tumors, and the bcl-2 gene family play a key role in the control of apoptosis.The bcl-2 gene family are composed by some bcl-2 homologous genes. Now 15 family members are found, and they are facilitative or suppressive on apoptosis respectively, and bcl-2 and bax are the most significance positive negative apoptosis-controlled genes.Bcl-2 is the first discovered apopotis-controlled gene in Mammalia,and its biological function is to extend cell survival and suppress apoptosis caused by many stimuluses.Bax can rival the function of bcl-2,and the bax overexpression can facilitate apoposis. The corresponding proteins of the bcl-2 gene family members can form dimerides by themself or one another. The interreactions of protein-protein control cell survival or apoptosis, and the interreaction of bcl-2 and bax is the critical. The dimeride of bcl-2 and bax can inactivate the function of bcl-2,so the ratio of bcl-2 and bax is one of the apopotis-controlled factors. Apoptosis and proliferation are the most important vital movements. They were considered completely unrelated in the past, and now apoptosis and proliferation are thought correlated and restricted each other, and controlled by a series of signals and its conduction mechanism. The imbalance of apoptosis and proliferation is the important factor of tumors. Cell proliferation augmentation and apoptosis rate stepping down, or no apoptosis that should be apoptosis resulting in more cells, this is one of the important mechanisms of tumors growth too.The past studies regarded that apoptosis only existed in malignant tumors, but recent years it is found that apoptosis is close correlated with uterine leiomyomas that belong to benign tumors. Since Matsuo et al the first time reported bcl-2 higher in progestational stage than in proliferative stage in 1997,many domestic and overseas scholars have studied the apopotis-controlled genes and its relationship with sexual hormone in uterine leiomyomas. LiWeiPing et al in 2000 reported in leiomyomas bcl-2 mRNA increased, bax mRNA decreased, bcl-2/bax mRNA increased;ER and PR had a positive correlation with bcl-2/bax mRNA, and PR showed more obvious correlation with bcl-2/bax mRNA. At present it is thought that uterine leiomyomas are benign tumors, but there is anormaly apoptosis in leiomyomas. Sexual hormone uterine leiomyomas dependent on promote cell proliferation by some mechanisms, meanwhile especially progesterone (P) suppress apoptosis by controllingbcl-2 and bax,then contribute to the more leiomyoma cells indirectly. This is one of the important mechanisms of leiomyoma production and growth.Animal models are the important instrumentals to study the pathogenesies and therapies of human diseases. Comparing to clinical studies, there are less studies of animal models for uterine leiomyomas, but the studies have a increasing tendency year after year. Now there are mainly three animal models for uterine leiomyomas: the model of treatment with exogenous sexual hormone in guinea pigs, the model of the transgenic mice, and the model of spontaneous Eker rats. Because of limited conditions, only the model of treatment with exogenous sexual hormone is used in domestic. The model have the disadvantage of long-time formation, but the pathomorphism appearances resemble with human uterine leiomyomas, so the model has some application values. Guinea pigs are the first animal to use for the model of treatment with exogenous sexual hormone, but besides guinea pigs, rats are often used in domestic.There are no public reports about apoptosis and its controlled factors in the animal models for uterine leiomyomas,and at the same time ,the differences between guinea pigs and rats as animal models for uterine leiomyomas are not reported So this thesis treated guinea pigs and rats with exogenous sexual hormone to replicat uterine leiomyoma. Then studying apoptosis and its controlled factors in the animal models to illustrat the resemblances between animal models and human uterine leiomyoma. Meanwhile detecting the differences between guinea pigs and rats as animal models for uterine leiomyomas1. ObjectiveReplicating rats model and guinea pigs model for uterine leiomyomas. Studying apoptosis and its controlled factors in the animal models to illustrate the resemblances between animal models and human uterine leiomyoma.Meanwhile detecting the differences between guinea pigs and rats as the animal model for uterine leiomyomas.2. MethodIn rats and guinea pigs, pretreatment with estradiol (E2) intramuscularly for 3 months followed by combination treatment with E2 and P replicated uterine leiomyomas. The studies of aptptosis included the observation of apoptosis morphology, the observation of apoptosis biochemistry features, and the detection of apoptosis-controlled genes bcl-2 and bax. The morphology of apoptosis was observed in paraffin section by HE staining through light microscope. DNA was extracted from uterus by the kit, and to have a gel electrophoresis, then to analyze the biochemistry feature of DNA breakage of apoptosis by picture analysator. The expressions of bcl-2 and bax were detected by immunohistochemistry SABC in rats model and ELISA in guinea pigs model. In guinea pigs model the expreesions of bcl-2 and bax were detected in both uterine body and uterine root, and the ratio of bcl-2 and bax was acquired. The study of aptptosis controlled-factors included the detection of E2 and P ,the observation of uterine economy,and the observation of uterine pathomorphism. The serum concentrations ofE2 and P were detected by radioimmunoassay, and the dependablities between E2n P and bcl-2> bax> bcl-2/bax were analyzed. The observation of uterine economy included the weight and diameter of uterus, and the observation of uterine pathomorphism included the thickness of uterine smooth muscle and so on. 3. Results3.1 The study of apoptosis3.1.1 The observation of apoptosis morphologyThere were no apoptosis cells in uterine smooth muscle of rats model and guinea pigs model, and apoptosis cells occasionally scattered in endomembrane, appeared blue-black nucleus, rufous endochylema, compressed and fragmented chromatinic etc.3.1.2 The observation of apoptosis biochemistry featuresThe electrophoresis of DNA from uterus of rats model demonstrated a macromolecule strap very near handholes, but there did not appear the typical biochemistry feature of apoptosis -"ladder" strap.3.1.3 The detection of apoptosis-controlled genesImmunohistochemistry in rats appeared brown-yellow granas in both the model and the normal, representing bcl-2 and bax positive coloration. Brown-yellow granas mainly located in cytoplasm, and scattered in uterine smooth muscle not in endomembrane and serosa. Using software analysis of picture analysator, compared with uterine smooth muscle of the normal control, the number of bcl-2 protein positive cells was significantly increased, and positive signal was significantly stronger;the number of bax protein positive cells was significantly lower, and positive signal was significantly weaker in the model.ELISA in guinea pigs demonstrated both the model and the normal control had the expressions of bcl-2 and bax. Compared with the normal control, the bcl-2 expression in uterine root and body of the model was obviously higher, the bax expression was obviously lower, and the radio of bcl-2/bax was obviously higher. There were no marked changes between uterine root and body of the model.3.2 The study of apoptosis-controlled factors3.2.1 The serum concentrations of E2 and PRats model demonstrated, compared with the normal control, the serum concentration of E2 and E2/P were significantly higher, and the serum concentration of P only had a tendency of increase.Guinea pigs model demonstrated, compared with the normal control, the serum concentration of E2 was significantly higher. The serum concentration of P and E2/P only had a tendency of increase. The serum concentration of P had a positive correlation with bcl-2/bax of uterine body.3.2.2 The observation of uterine economy 3.2.2.1 The weight and diameter of uterusCompared with the normal control, rats model and guinea pigs model had the same changes: the weight and the index of uterus were significantly increased;the diametes of uterus root were significantly increased. 3.2.2.2 The gross appearance observation of uterusCompared with the normal control, uterus of rats model was thickened obviously, especially the root swelled evidently.Compared with the normal control, uterus of guinea pigs model was thickened obviously, especially the root was swelled evidently. Uterine wall was hyperaemic, congestive and uneven in color. 3.2.3 The microscope pathomorphism observation of uterusCompared with the normal control, uterine smooth muscle and muscle bundle of rats model were thickened obviously;the number of uterine smooth muscle cells was increased, volume disparity and nucleus thickness.Compared with the normal control, uterine smooth muscle of guinea pigs model was thickened obviously, muscle bundle was thickened, irregular arrangement and scattered whirlpool frame;the number of uterine smooth muscle cells was increased, and the volume ratio of endochylema and nucleus was imbalance, volume disparity and nucleus thickness. 3.3 The comparison of successful marks in animal modelsThe same:Both rats model and guinea pigs model demonstrated: the serum concentration of E2 was significantly higher;uterine weigh was increased;uterine root was swelled and thicked;uterine smooth muscle and muscle bundle were marked thicken;the number of uterine smooth muscle cells was increased.Compared with rats model, guinea pigs model demonstrated: uterine root was swelled, and uterine wall was hyperaemic and congestive more obviously;uterine pathomorphism changes were more serious,such as muscle bundle irregular arrangement,scattered whirlpool frame, and uterine smooth muscle cells bolus aggregation and so on. 4. Conclusion4.1 There was apoptosis suppressed in rats model and guinea pigs model for uterine leiomyomas,controlled by bcl-2 and bax,and P could be one of the main factors that affected the radio of bcl-2/bax.This demonstrated the model had resemblances with the human disease.4.2 Both rats and guinea pigs could be preferred animals for uterine leiomyomas.Guinea pigs were more sensitive to sex hormone than rats.The most detected dates in rats model had smaller dispersions,and this demonstrated rats model were stable than guinea pigs.