| Prem ature ovarian failure (POF)refers to a state of hypo-estrogen and h ypso-gonadotrophin before 40 years old. It is mainly characterized by amenor rhoea as well as infertility. And it appears a series of perimenopausal sympt oms like hectic fever and hyperhidrosis, restlessness and insomnia, dry and u nsmooth vagina, dyspareunia, osteoporosis which brings patients great pains and seriously affects female quality of life , physical and mental health. Its disease incidence occupies 1%3% in women and 2%10% of secondary amenorrhe a, family history matters occasionally,which is the hot and difficult spot i n today' s healthy reproduction research.This research first arranges TCM ancient books and records and literatur e systematically under the direction of professor zhang yu zhen , and raise u p the arguing point of POF pathomechanism "spleen and kidney deficiency, dep ressed liver-qi and blood stasis, chongren meridian deficiency" based on th e principle of invigorating the kidney and spleen, regulating the liver . Jia Jian Gui Shen Pill is used to treat POF and approach the therapeutic action clinically. We use the D-galactose to POF rat model as research objectives to approach the curative effects and mechanism. And the research is carried o n by symptom score , reproduction endocrine level(FSH,E2), ovary coherent cy tokine(IL-2 , TNF-α, VEGF,INHB), ovary doppler blood current index numbe r etc.Part 1 Literature StudiesThe etiology of POF is unclear, maybe due to genetic factor, gonadotropic hormone function obstacle, immunologic injury, inborn azymia, environmental agent damage, viral infection or other factors which result in less primordi al follicle quantity, follicular atresia increase or acceleration, follicula r dysmaturity. And the treatment method is estrogen and progestorone replacem ent therapy, induced ovulation, egg-given assisting technology, ovary allogra ft, application of immune depressant etc.There is' t a clear name for POF in traditional Chinese medical science. It is united into amenorrhea,depleted blood, menstruation breakdown before ag e, infertility category etc. But ancient books .records and literature contai n abundant relative contents. This research is based on the development law o f TCM gynecology and recognition to put pertinent literature in order from e arly QIN dynasty to contemporary age which is divided into five stages and p rovide theory evidence for TCM research on this disease. To sum up these etio logical factors , it is because of congenital and postnatal condition like co ldness, heat , dampness invasion, affection factors or life injury which lead s to the viscera malfuntion .deficiency of heart , liver .spleen and kidney , blood and qi disturbance, impairment of thoroughfare and conception vessel t hat is the functional presenility of kidney-tiangui-chongren uterus reproduc tion axis. Now we study this disease mostly on clinical case observation and animal experiment. The method of TCM treating POF is : TCM differentiation ofsymptoms and signs for classification of syndrome, fixed formula adding or s ubstracting, Chinese traditional patent medicine therapy, combined treatmentof traditional Chinese medicine and western medicine etc. Part 2 Clinical StudiesObjective: 22 women with POF are chosen as case-control group;Normal gr oup includes 20 healthy and grown-up women whose periods are regular.Method: The therapeutic group is treated with Jia Jian Gui Shen Pill whi ch function is tonifying the kidney and invigorating the spleen,regulating t he liver and promoting blood flow. Symptoms are observed pre-and post-treatm ent, and score them;Electrochemistry radiation method has been used to examin e follicle-stimulating hormone (FSH), luteinising hormone (LH) and estradiol(E2) pre and post treatment. Tumor necrosis factor alpha (TNF-a) and interleukin-2 (IL-2) have been checked by enzyme-linked immunosorbent assay (ELIS A) pre and post treatment. The blood flow parametes involving PSV, PI and RIof both ovary arteries are measured by pelvic ultrasonography.Results: Preceding treatment, symptoms of flush and sweating, unsmooth a nd dry vaginal, waist and knee sour and weak, irritability and tantrum , bad s leep and much dreams are obvious. After treatment these symptoms are signifi cantly better than before (P<0. 05). The symptoms like hair withered luxated t ooth, palpitation and chest distress, forgetfulness doesn' t make much progr ess.There is no significant difference comparing to before(P>0. 05) , and theintegral calculus of patients' symptom obviously reduces comparing to the pre-treatment which suggests great difference (P<0. 01) .The patients in th e therapeutic group post-treatment ,2 cases fully recover from an illness, e xcellence is 7 cases, effectiveness is 9 cases, unavailability is 4 cases, to tal effective rate 81.82%.Patients serum in therapeutic group FSHn LH is obviouisly higher than t hat of control group,as to E2 it is vice versa, there is significant differen ce in both two items between the two groups (P<0. 01) . The comparison betwee n therapeutic excellence group and utility group on FSH-, Uk E2 level is of no significant difference (P>0. 01) before treatment. FSH and LH of excellen ce group after treatment is obviously lower than that of utility group and E 2 is obviously higher in the first group which suggests significant differen ce (P<0. 01) .Patients serum TNF-aand IL-2 in therapeutic group is much higher thanthat of control group which suggests great significance (P<0. 01) . Comparin g Therapeutic excellence group TNF-aand IL-2 to utility group ,the differen ce is of no difference pre-treatment .While TNF-a and IL-2 both obviously r educes, moreover, lower than utility group, there is great difference comparingtwo groups.The blood flow of both ovary arteries in POF patients is lower in thera peutice group than that of normal group . The difference is great between twogroups (P<0. 01);Pulsatility index is greatly higher than that of normal group as well as resistent index, all of which suggest significant differenc e (P<0.05) .Comparing two groups (excellence group and utility group ),both ovarie s blood flow is of no difference pre-treatment (P>0. 05) ,and significant dif ference post-treatment because of its rising. Great difference happens betwe en two groups (P<0. 01);There is no great difference between pulsatility index pre-treatment (P>0. 05) , but it reduces post-treatment which suggestsgreat difference (P<0. 05) , the same with resistent index. Part 3 Empirical studyMethod:To divide healthy female sex SD rat into seven groups ,the rats' napes are injected subcutaneously D-galactose physiologic saline solution 15 0 mg/(kg/d)in model group and therapeutic group;In blank case-control groupthey are injected same volume physiological saline, one time/d, 56 days succ essively. After 56 successive days' medication,they are fasting 12 hours bef ore blood sample taken in orbital vein with etherization on the 57th day , th en separate the blood serum after centrifugalization (2500x) and detect thecontent of FSHk E2> VEGF> INH with radioimmunity method. The rats are put t o death by cervical uertebra dislocated after the sample taken in the eye ba 11. We put their both ovaries and thoracic gland on the electronic balance a nd calculate the organ index and retain them in formalin, gradient alcoholicdehydration, paraffin imbedding, microtome section, routine HE dyeing and th en observe it under the light microscope.Results: Model group, diethylstibestrol aqueous solution group, Jia JianGui Shen Pill low dose group all lose their weight when compared to the nor mal group;ZI Shen Yu Tai pill low- dosage group,ZI Shen Yu Tai pill high-do sage group and Jia Jian Gui Shen Pill high-dosage group also lose weight whe n compared to the normal group;Diethylstibestrol aqueous solution group, gu i-shen pill low-dosage group, ZI Shen Yu Tai pill low-dosage group lose lessweight than that of model group, the differences are significant (P<0. 05.. P<0.01 , P<0.01) .The ovary index number of model group, diethylstibestrol aqueous soluti on group and Jia Jian Gui Shen Pill low-dosage group decreases more signific antly(P<0. 05> P<0. 01 % P<0. 01) when compared to the normal group. Ovary ind ex number decreases significantly when comparing model group to ZI Shen Yu T ai pill high dose group and gui-shen pill high dose group (P<0. 05);Ovary index number of diethylstibestrol aqueous solution group also decreases compa red to ZI Shen Yu Tai pill high dose group and Jia Jian Gui Shen Pill high d ose group (P<0. 01) , but difference between Jia Jian Gui Shen Pill low dose g roup and ZI Shen Yu Tai pill low dose group is not significant (P>0. 05) .Comparing model group to normal group thoracic gland index number decre ases significantly (P<0. 01);That of model group also decrease when comparin g them together as the diethylstibestrol aqueous solution group, Jia Jian Gu i Shen Pill low dose group and zishenyutai pill low dose group (P<0. 05) .Comparing to the normal group, the FSH and E2 level of the model group b oth descend, the differences are significant (P<0. 01. P<0.01);the FSH and E2 level of the gui-shen pill high dose group rise up compared to the model gr oup, the difference is significant (P<0. 01, P<0.01).The VEGF and INHB level of the model group descends comparing to the nor mal group, the differences are significant (P<0. 01, P<0. 01);VEGF and INHB 1 evel of the model group ascends comparing to the diethylstibestrol aqueous s olution group, the difference is significant (P<0. 01, P<0. 01), VEGF and INHB level of the gui-shen pill high dose group rises up when compared to the di ethylstibestrol aqueous solution group, difference is significant (P<0. 05) , but it is not great between gui-shen pill high dose group and the normal gr oup (P>0.05) .The primary follicle number, secondary follicle number and the corepus 1 uteum number of the model group all descends greatly than the normal group, the difference is significant (P<0. 05^ P<0. OK P<0. 01). The primary follicle number, secondary follicle number and the corepus luteum number of the dieth ylstibestrol aqueous solution group all decrease significantly than the gui-shen pill high dose group. There is great difference (P<0. 0U P<0. OK P<0. 01). Part 4 Conclusions:1. Jia Jian Gui Shen Pill can significantly improve the perimenopause sy mptoms of the premature ovarian failure(POF) patients, such as heat and swea t, dryness of the vagina, irritation, waist and knee sour and weak, insomnia and multiple dream, etc. Thus improve the life quality of the patients, we think Jia Jian Gui Shen Pill deploy its effective function by adjusting the kidney-tiangui- chong and ren meridian-ovary reproduction axis.2. Jia Jian Gui Shen Pill can improve the ovary patients' serum endocrin e level, reduce the FSH level and increase E2 level which proves that the me thod of nourishing the kidney and strengthen ing the spleen, regulating live r and promoting blood flow can improve the function of ovary, adjust Feedbac k mechanisms of the hypothalamus-pituitary gland.3. With the treatment of Jia Jian Gui Shen Pill which function is tonifyi ng the kidney and invigorating the spleen,regulating the liver and promotingblood flow,we observe the POF patients' ovary blood flow through color dop pier. And it proves that this method can improve the blood supply for patient s' ovary, promote the follicular development , increase the secretion of E2 a nd reduce abnormally increasing FSH so as to improve the function of ovary . Therefore this method could obviously improve general symptom of POF perimen opausal patients and also restore the regularity of patients' menstruation,efficiently imrpove patients' life quanlity4. This research firstly adopt D—lactose subcutaneous injection in rat s' nape to make POF rats model which is already testified by pathology . Thetreatment of intragastric administration by Jia Jian Gui Shen Pill which f unction is tonifying the kidney and invigorating the spleen, regulating the 1 iver and promoting blood flow can improve the blood serum VEGF^ INHB level o f POF rats , lower FSH level and inhibit follicular atresia which certificat es that TCM which has the function of tonifing the kidney and invagorating t he spleen , nourishing blood and promoting blood flow can improve ovarian va scularization which is good to the ovary blood supply which suggests that TC M has the function of estrogen hormonelike and restore the ovary function byregulating the hypothalamic-pituitary-ovarium axis through controlling repr oduction and endocrine function. |
PDF Full Text Request