| BackgroundEndometriosis is a common and complicated disease that mainly affects women of reproductive age, and is closely associated with algopareunia, infertility and menalgia. Though the disease presents benign histopathologic changes, it also displays similar biologic behavior with malignant cancer and its etiology and mechanism was unknown. There is no effective therapy at present. Kanglaite Soft Capsule discovered in our country has been widely applied to clinical therapy as a second class anticancer Chinese medicine. It has been observed in many studies that this drug can kill multiple types of neoplastic cells and induce the development of apoptosis. Besides, It has been suggested that increased anti-apoptosis and decreased apoptosis may lead to ectopic survival and implantation of endometrial cells and the development of endometriosis. Therefore, based on these findings, our study is a(?)med to objectively evaluate the exact effect of Kanglaite Soft Capsule on apoptosis in endometrial cells with the rat model of endometriosis.ObjectivesHere we compared the expression of apoptosis-related proteins Bcl-2, Bax in rat models of endometriosis treated with three different dosages of Kanglaite Soft Capsule, so as to investigate the mechanism of Kanglaite Soft Capsule on apoptosis in endometrial cells, and to provide proof to clinical therapy.MethodsWe built the rat models of endometriosis by self-transplantation of endometrium, and divided these rat models into different groups mainly by the dosage they took Kanglaite Soft Capsule:the model group, the small dosage of Kanglaite group, the moderate dosage of Kanglaite group, the large dosage of Kanglaite group and the danazol group. Each group includes10rats, and we use another10rats as the normal control group. The small dosage of Kanglaite group was given the drug with a dosage of0.25g/kg, the moderate dosage of Kanglaite group was given the drug with a dosage of0.5g/kg, and the large dosage of Kanglaite group was given the drug with a dosage of1.0g/kg. The danazol group was given the danazol suspension with a dosage of60mg/kg. And both the model group and normal control group were given physiological saline. Each group was given the drugs by intragastric administration once a day, persisting for continuous4weeks. And all the rats were killed in their rut phase. We observed the histopathologic changes of ectopic endometrium by light microscope, and compared the expression of Bax and Bcl-2in ectopic and eutopic endometrial tissues by immunohistochemical technique.Results1. The rat models of endometriosis were successfully built by the method of self-transplantation of uterine tissue with a survival rate of89%.2. After administration of the Kanglaite Soft Capsule for4weeks, the growth of ectopic endometrium was obviously suppressed and the ectopic leision tissue showed ischemic changes such as degeneration and apoptosis under the light microscope.3. The Bcl-2protein displayed as buffy granules and was mainly located in cytoplasm under the light microscope. The Bcl-2expression of ectopic endometrial tissue in model group was significantly higher compared with the normal control group, moderate dosage of Kanglaite group, the large dosage of Kanglaite group and the danazol group(P<0.01,P<0.01,P<0.05,P<0.01), but showed no significant difference compared with the small dosage of Kanglaite group(P>0.05). The Bcl-2expression of ectopic endometrial tissue in the large dosage of Kanglaite group showed no significant difference compared with the danazol group and the normal control group respectively (P>0.05, P>0.05). There is a significant difference of Bcl-2expression of ectopic endometrial tissue between moderate dosage of Kanglaite group, the small dosage of Kanglaite group, the danazol group and the normal control group(P<0.05).4. The Bax protein displayed as buffy granules and was mainly located in cytoplasm under the light microscope. There was a significant low Bax expression of ectopic endometrial tissue in model group compared with the normal control group (P<0.01). However, The Bax protein of ectopic endometrial tissue in moderate dosage of Kanglaite group, the large dosage of Kanglaite group and the danazol group were significantly highly expressed compared with the model group(P<0.01, P<0.01,P<0.05, P<0.01). There is no significant difference of Bax expression of ectopic endometrial tissue between the small dosage of Kanglaite group and the model group (P>0.05). The Bax expression of ectopic endometrial tissue in the large dosage of Kanglaite group showed no significant difference compared with the danazol group and the normal control group respectively (P>0.05, P>0.05). There is a significant difference of Bax expression of ectopic endometrial tissue between moderate dosage of Kanglaite group, the small dosage of Kanglaite group, the danazol group and the normal control group (P<0.05).ConclusionsKanglaite Soft Capsule could inhabit the endometriotic growth in the rat model of endometriosis and it might be medicated by decreasing the expression of the anti-apoptotic protein Bcl-2and enhancing the expression of the pro-apoptotic proteins Bax in the endometrial tissue. |
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