| Objective : The endometriosis(EMs) is a common disease in child-bearing women, its prevalence increases year by year, badly affecting the women's physical and mental health. Up to now, its pathogenesis is still unclear. Though EMs is a benign lesion, its characteristic of extensive plantation and recurring are as same as malignant tumor. In these years, the studies indicated that the hypoxic state was an important factor in the development of malignant tumor. It has been proved that the hypoxic state played an importance role on the process of malignant tumor's generation. Our studies have proved that the therapeutic method of tonifying kidney, warming yang and dissolving stasis can decrease the endometriosis lesion, relax the pelvic adhesion,relieve the pelvic stagnated blood and pelvic pain, regulate the ovarian functions. Therefore, we aimed at further exploring underlying problems as follows, 1.whether there were hypoxic state in the endometriosis region from the three different diseased lesion(peritoneal endometriosis, ovarian endometrial cyst and adenomyosis) 2. The relation between the hypoxic state and adhesion, invasion and vascularization. 3.Observing the effect of the herbs for tonifying kidney, warming yang and dissolving stasis on dysmenorrhea and quality of life in patients with EMs;4.Establishing the model of endometriosis, studying the effect of the herbs with tonifying kidney, warming yang and dissolving stasis on it, to further explore its active mechanism.Method:1Clinical research(1)The study group:The operational patients with endometriosis admitted to the Bethune International Hospital, Shijiazhuang hospital of Obstetric & gynecology and Hebei Province hospital of Traditional Chinese Medicine consistent with the EMs included criteria during January to December in 2007 were selected, to make the final diagnosis through examination with laparoscope and exp. lap. Among them, there were 8 cases of peritoneal endometriosis, 7 cases of ovarian endometriosis and 9 adenomyosis, collected the ectopic endometrial tissue during the operation which confirmed by the pathologic detection after operation.The control group:the 6 patients with uterus myoma admitted to hospital in synchronization were selected as the control group, detected as normal endometrium by pathological detection.All the patients were informed consent,their age distribution were balanced,and no statistic difference,with comparability. All the sample were kept in the late stage of secretion.The methods of immunohistochemistry streptomycete protein- Oxidase(SP) were applied to detect the expression of vascular endothelial growth factor(CD34), cell adhesion factor(CD54), glucose transporter-1(GLUT-1), matrix metalloproteinase-2(MMPS-2) in endometrium;the semi quantitative reverse transcription polymerase chain reaction(RT-PCR)were used to detect the expression of Cu2Zn2SOD,SOD in endometrium in each groups. 2clinical research(2)46 patients with EMs manifested by dysmenorrheal were randomly divided into treated group (i.e. herbal group) and control group(i.e. western medicine group), there were 23 cases in each group, the herbs for tonifying kidney, warming yang and dissolving stasis were administrated to the patients in treated group, gestrinone was taken by the patients in control group, all of them were treated for 3 menstrual cycles. According to the WHOQOI-100 and WHOQOL-BREF measuring scale about quality of life , the state of quality of life were observed in these two groups; The visual vague scale was adopted to survey the degree to improve the dysmenorrhea.3 Animal Experiment 60 healthy sanitation female Wistar rat with normal estrous cycle were selected,200±20g in weight,according to the result of vaginal smear examination, make the model with operation at estrum to duplicate the model of endometriosis according to the Wang Yan-ping's method, the abdomen of the sham operated group were opened and closed with no management. The success model rats were divided into four groups according to the table of random digit, named high-dose group treated with herbs(abbreviated high-dose group), low-dose group treated with herbs(abbreviated low-dose group), the model control group(abbreviated control group),the treated group with danazol(abbreviated western medicine group),10 rats in each group. The rats in high-dose group and low dose group were given 15.41g/ kg and 61.76g/ kg by intragastric administration(equal to 5 and 20 times of adult dosage in clinic respectively)with the herbs of tonifying kidney, warming yang and dissolving stasis once daily for 4 weeks;the rats of western medicine were given 100mg/kg/d water solution with intragastric administration for 4 weeks;the rats of sham operation group were given the same voluminal distilled water. Fasting diet 8 hours after the last administration,decapitated the rats in estrous,under the sterile operation, cut and opened the belly to take out the endometrium of each groups, absorbed the blood, fixed in the solution of 4% paraformaldehyde,took the routine paraffin imbedding,made 5μm serial sections,carried out the immunohistochemical stain,and assayed the expression of CD34,CD54,GLUT-1 and MMPS-2 in the endometrium;kept the rest part of endometrium in nitrogen canister immediately,which used to detect the expression of SOD.Results:The results of clinical empirical study1 The different diseased region of EMs(the peritoneal ectopic endometriosis, ovarian endometriosis and adenomyosis), the hypoxic maker in regional tissues----the contents of glucose transporter-1(GLUT-1) and copper-zinc erythrocuprein(SOD) in theses three groups were significantly higher than that in control group(P=0.002,P<0.05; P=0.001,P<0.05). While the hypoxic state were no statistic difference in various tissues, the multiple comparisons among the three groups were no statistic difference (P>0.05)。2 There were negative correlation between SOD and ICAM-1(CD54) among the various tissues in diseased region(rs=-0.476,P =0.019,P <0.05);there were positive correlation between GLUT-1 and ICAM-1(CD54) in various tissues of diseased regions(rs=0.426,P=0.012,P<0.05).3 There were negative correlation between the SOD and MMP-2 (rs=-0.468,P =0.017,P <0.05);There were positive correlation between GLUT-1 and ICAM-1(CD54) in various tissues of diseased regions(rs=0.428,P=0.014, P <0.05).4 There were positive correlation between SOD and CD34(rs=0.468,P=0.017,P<0.05); there were negative correlation between GLUT-1 and CD34(rs=-0.428,P=0.019,P <0.05).The results of clinical research1 The comparison of scales on the quality of life between the two groups Except the environment( there were no statistically different between the two groups in the aspect of environment. P>0.05), the scales on each aspect in the herbal group were statistically different from that in the western medicine group P<0.05), the quality of life in patients in the herbal group were higher than that in the group of western medicine.2 The comparison of dysmenorrhea before and after treatment between the two groupsThere were 19 cases manifested as amenorrhea after administration in the group of western medicine, while their menstruation come again within the 3 months after drug withdrawal, there were no amenorrhea in the herbal group. After 3 mouths'treatment, the dysmenorrhea were improved in each group with statistical difference(P<0.05). there were no statistical difference in the patients with mild dysmenorrhea between the two groups(P>0.05),while there were statistical difference in the patients with severe dysmenorrhea between the two groups. The improved condition on severe dysmenorrhea in herbal group are better than that in the group of western medicine, furthermore no presence of amenorrhea.The results of animal experimentThe EMD focus in the rats of endometriosis model were in the hypoxic state, the contents of SOD and GLUT-1 were obviously higher than that in control group, there were statistic differences compared with that in control group(P<0.01), the herbs of tonifying kidney, warming yang and dissolving stasis can significantly improve the hypoxic state in the tissues of ectopic endometrium(P<0.05), the same effect happened in the two groups, i.e. the low-dose group and high-dose group(P>0.05); there were no statistic differences in the role of improving the hypoxic state between the herbal group and western medicine group( P>0.05).Conclusions:1 The endometriosis in various diseased regions(peritoneal endometriosis , ovarian endometriosis and adenomyosis) were all in the hypoxic state.2 There were no significantly differences in the hypoxic state in various diseased regions.3 The hypoxic state in endometriosis were closely related to the capability of cell adhesion.4 The hypoxic state in various diseased regions were positive correlation to the invasive capability of ectopic cells.5 The hypoxic state were positive correlated to the capability of angiogenesis in different diseased region .6 The therapeutic methods of tonifying kidney, warming yang and dissolving stasis can significantly improve the symptom of dysmenorrheal and the quality of life.7 The therapeutic method of tonifying kidney, warming yang and dissolving stasis can significantly improve the hypoxic state in the model rats of endometriosis, and the herbs in therapeutic dose can improve the regional hypoxic state. The results showed that the therapeutic method of tonifying kidney, warming yang and dissolving stasis can cure endometriosis through improving the hypoxic state which may be one of the active mechanism of the therapeutic method of tonifying kidney, warming yang and dissolving stasis.
|
PDF Full Text Request