Exploration On Effect Of DANCHI Decoction On Endometriosis Patients After Conservative Surgery Based On "3A Process"

Objective:Through observing endometriosis recurrence in patients with TCM syndrome of Qi stagnation and blood stasis after6months of conservative surgery, and detecting protein expression of ICAM-1, MMP-9, VEGF in their eutopic endometrium as well as serum contents of ICAM-1, MMP-9, VEGF and CA125under intervention by traditional Chinese medicine Danchi Decoction or western medicine GnRH-a or gestrinone serving as a positive control, we assess expression change of above-mentioned factors and value their possible effect on endometriosis recurrence, thus explore the effect of Danchi Decoction on endometriosis patients after conservative surgery from the perspective of "3A process" and clarify the possible mechanism of inhibition effect on endometriosis recurrence of patients after conservative surgery by Danchi Decoction.Method:This research is a part of NSFC (Natural Science Foundation of China) general project named "Exploration on mechanisms of inhibition effect on endometriosis recurrence by Danchi Decoction based on eutopic endometrium and immunologic balance"(Project Number:30973769), and belongs to exploratory clinical fundamental research. Twenty cases are selected from patients with TCM syndrome of Qi stagnation and blood stasis who have undergone conservative laparoscopic surgery and been diagnosed as ovarian endometrioma in both Guang’anmen Hospital and Beijing Friendship Hospital during the whole year of2011. We randomly bring them into traditional Chinese medicine group (TCM) or western medicine group (WM) Besides, another10patients are chosen as members of normal control group (NC), who have also undergone laparoscopic surgery during the same time period and been diagnosed as simple ovarian cyst instead of endometriosis, and whose endometrial pathological examinations show no abnormal manifestation. Patients in TCM and WM groups all begin to take medication at the moment of entering group during1st to5th days of their first postoperative menstruation period, and all receive continuous medication for three months as well as follow-up until three months after drug withdrawal. Patients in TCM group are given oral Danchi Decoction one potion each day including their menstrual periods, while those in WM group are given subcutaneous injection of GnRH-a(Zoladex, i.e.goserelin,3.6milligrams per ampoule,1ampoule at a time, once every28days after the first injection) or oral gestrinone capsule (2.5milligrams per capsule, one capsule at a time, twice a week). Patients in NC group, who serve as the blank control, are given no drug intervention. We detect protein expression of ICAM-1, MMP-9, VEGF in the eutopic endometrium of patients in all groups at time of both preoperation and three months after drug withdrawal (only preoperation in NC group,5cases are selected from each group respectively)by immunohistochemical method, and detect serum contents of ICAM-1, MMP-9, VEGF and CA125in patients of all groups at time of preoperation, three months after medication, three months after drug withdrawal(only preoperation in NC group) by ELISA method. All experimental datum are going through statistical processing with statistical analysis software named SPSS16.0. All measurement datum are expressed in the form of mean±standard deviation (x±s), and the difference is regarded as statistically significant when P<0.05.Results:1. Three months after drug withdrawal, while the overall observation time period is6to7.5months after surgery and the average observation time period is (6.66±0.55) months, endometriosis recurrence occurs in2cases including1in TCM group and1in WM group, whose recurrence time is7.5months after surgery and6months after surgery respectively, and whose recurrence rate is10%(1/10) and20%(2/10) respectively. Recurrent patients are both found manifestation of chocolate cyst in their pelvic B ultrasound image as well as symptom of recurrent dysmenorrhea. Three months after drug withdrawal, protein expression of ICAM-1, MMP-9, VEGF in the endometrium of recurrent patients is all slightly lower than that at time of preoperation, while the decreasing range is all significantly lower than that of patients without recurrence, and protein expression of ICAM-1, MMP-9, VEGF in the endometrium of recurrent patients is still significantly higher than the average level of NC group. Three months after drug withdrawal, serum contents of ICAM-1, MMP-9, VEGF and CA125of recurrent patients are all higher than those at time of three months after medication to different degree, while serum contents of ICAM-1, MMP-9, VEGF and CA125of patients without recurrence are mostly lower than those at time of three months after medication to different degree. Three months after drug withdrawal, serum contents of ICAM-1, MMP-9, VEGF and CA125of recurrent patients are still significantly higher than the average level of NC group, but is lower than those at time of preoperation.2. Before surgery, protein expression of ICAM-1, MMP-9, VEGF in the eutopic endometrium of patients in TCM and WM groups is all significantly higher than that in NC group (P<0.05), and comparison between TCM and WM groups shows that their difference isn’t statistically significant (P>0.05). Three months after drug withdrawal, protein expression of ICAM-1, MMP-9, VEGF in the eutopic endometrium of patients in TCM and WM groups is all significantly lower than that at time of preoperation (P<0.05), and comparison between TCM and NC groups shows that their difference isn’t statistically significant (P>0.05). Three months after drug withdrawal, protein expression of ICAM-1, MMP-9, VEGF in the eutopic endometrium of patients in WM group is still significantly higher than that in both NC and TCM groups (P<0.05). Protein expression difference of ICAM-1, VEGF in the eutopic endometrium of patients in TCM group at time of preoperation and three months after drug withdrawal is statistically higher than that in WM group (P<0.05).3. Before surgery, serum contents of ICAM-1, MMP-9, VEGF in TCM and WM groups are all significantly higher than those in NC group (P<0.05), and comparison between TCM and WM groups shows that their difference isn’t statistically significant (P>0.05). Three months after medication and three months after drug withdrawal, serum contents of ICAM-1, MMP-9, VEGF in TCM and WM groups are all significantly lower than those at time of preoperation (P<0.05). Three months after drug withdrawal, serum content of MMP-9in TCM group is also significantly lower than that at time of three months after medication (P<0.05). Three months after medication, serum contents of ICAM-1, MMP-9, VEGF in TCM and WM groups are still significantly higher than those in NC group (P<0.05). Three months after drug withdrawal, comparison of serum content of ICAM-1between TCM and NC groups shows that their difference isn’t statistically significant (P>0.05), while serum contents of MMP-9, VEGF in TCM group and serum contents of ICAM-1, MMP-9, VEGF in WM group are still significantly higher than those in NC group (P<0.05) Comparison of serum content difference of MMP-9at time of preoperation and three months after medication between TCM and WM groups shows that their difference isn’t statistically significant (P<0.05). Serum content difference of MMP-9in patients of TCM group at time of preoperation and three months after drug withdrawal is statistically lower than that in WM group (P<0.05). Comparison of down-regulating effect on serum contents of ICAM-1, MMP-9, VEGF by drugs among three time points of preoperation, three months after medication, three months after drug withdrawal shows that their difference is statistically significant (P<0.05). Comparison of down-regulating effect on serum contents of ICAM-1, MMP-9, VEGF between TCM and WM therapy shows that their difference isn’t statistically significant (P>0.05)4. Before surgery, serum content of CA125in TCM and WM groups is all significantly higher than that in NC group (P<0.05), and comparison between TCM and WM groups shows that their difference isn’t statistically significant (P>0.05) Three months after medication and three months after drug withdrawal, serum content of CA125in TCM and WM group is all statistically lower than that at time of preoperation (P<0.05). Three months after medication, serum content of CA125in TCM group is still significantly higher than that in NC group (P<0.05), and comparison between WM and NC groups shows that their difference isn’t statistically significant(P>0.05), and serum content of CA125in WM group is significantly lower than that in TCM group (P<0.05). Three months after drug withdrawal, serum content of CA125in WM group is significantly higher than that at time of three months after medication(P<0.05), and comparisons between TCM and NC groups as well as WM and NC groups all show that their differences aren’t statistically significant (P>0.05). Comparison of down-regulating effect on serum contents of CA125by drugs among three time points of preoperation, three months after medication, three months after drug withdrawal shows that their difference is statistically significant (P<0.05).Comparison of down-regulating effect on serum contents of CA125between TCM and WM therapy shows that their difference isn’t statistically significant (P>0.05)Conclusions:1. The abnormally high expression of core factors in "3A process" including ICAM-1, MMP-9, VEGF in the eutopic endometrium and serum may play a certain role in recurrence of endometriosis patients after conservative surgery. As an assisted index in postoperative monitoring of curative effect, serum content of CA125is of certain value in recurrence judgement.2. Traditional Chinese medicine Danchi Decoction could down-regulate protein expression of ICAM-1, MMP-9, VEGF in the eutopic endometrium as well as serum contents of ICAM-1. MMP-9, VEGF and CA125in patients with endometriosis to different degree, thus inhibiting recurrence of endometriosis patients with TCM syndrome of Qi stagnation and blood stasis after conservative surgery to a certain degree. Compared with currently acknowledged first-line positive drugs of western medicine GnRH-a or gestrinone, Danchi Decoction may has certain superiority, which manifests as a more stable, lasting and cumulative effect.3. The possible mechanisms of inhibition effect on recurrence of endometriosis patients after conservative surgery by Danchi Decoction may be adjusting abnormal protein expression in the eutopic endometrium and weakening the ability of adhesion, invasiveness and neovascularization of endometrial cells, thus blocking "3A process" as "attachment-aggression-angiogenesis" and inhibiting activity of ectopic lesions.4. This research explores mechanisms of inhibition effect on endometriosis recurrence after conservative surgery by Danchi Decoction including intervening eutopic endometrium and blocking "3A process" from the perspective of "preventive treatment of disease", laying certain foundation for further research of its mechanisms as well as further development of clinical new drugs.