| Dysfunctional uterine bleeding, also called DUB, is abnormal uterine bleeding which was caused by organic disease of non-reproductive organs or systemic diseases. Its incidence rate approximately reaches10%in the gynecological clinic. DUB is clinically divided into two kinds, anovulatory and ovulatory dysfunctional uterine bleeding, and the ovulatory DUB accounts for20%-30%of all; it’s more common in women of childbearing age. The clinical manifestations of ovulatory DUB are high menstrual flow, prolonged menstruation, irregular bleeding between menstrual period and so on. It has lingering course and complex etiology, seriously affects the normal lives of the patients.Quyu hemostasis granules is derived from clinical prescription, which is composed of nine kinds of Chinese medicine including Sanqi, Puhuang, Baizhu, Fried Lingzhi. The efficacy of Sanqi is bleeding-stopping without leaving gore. Puhuang can stop bleeding; Baizhu is able to invigorating spleen and supplementing qi. Wulingzhi can cure blood stasis, fried one can be used to stop bleeding. The whole formula plays effects of bleeding-stopping, stasis-removing, spleen-strengthening and qi-benefiting. It can be used for high menstrual flow, prolonged menstruation, abdominal pain and blood clots which are caused by qi deficiency and blood stasis. The high menstrual flow of ovulatory dysfunctional uterine bleeding is common in patients with above symptoms.Rat DUB model to the experimental observation of Quyu hemostasis granules the model rat uterine bleeding amount, observed Quyu hemostasis granules of normal animals and animals coagulation disorder coagulation system, observed Quyu stop bleeding particles on hemorheology of acute blood stasis model. In addition, the experimental use of immunohistochemistry and molecular biology techniques, focusing on Quyu hemostasis granules DUB model rat uterine prostaglandins and fibrinolytic factors research "Quyu hemostasis granules" animal uterus contraction and blood flow from the role and mechanism of multiple aspects of the treatment of Quyu hemostasis granules DUB study and discussionThis thesis is divided into two main sections: Section1The treatment effect of Quyu hemostasis granules on the ovulatory dysfunctional uterine bleeding1.1The treatment effect of Quyu hemostasis granules on the uterine bleeding of ovulatory DUB model ratThe ovulatory DUB model in rat was induced by abortion in early pregnancy rats of drug. The colorimetry was used to measure the total uterine bleeding after7days of modeling. The results show that compared with the model group, the low and middle dose of Quyu hemostasis granules could significantly reduce the uterine bleeding of ovulatory DUB model rat.1.2The effect of Quyu hemostasis granules on coagulation function of miceThe normal mice and warfarin-induced coagulation model mice were observed respectively to determine the effect of Quyu hemostasis granules on coagulation function of mice. The results show that compared with the control group, Quyu hemostasis granules low, middle and high dose could shorten the bleeding time and coagulation time in mice after administered for5days(P<0.01), suggesting that Quyu hemostasis granules can enhanced the coagulation of normal animals. Compared with the model group, Quyu hemostasis granules low, middle and high dose could significantly shorten the bleeding time and coagulation time in warfarin-induced coagulation model mice after administered for5days (P<0.01), indicating that Quyu hemostasis granules can enhanced the coagulation of warfarin-induced coagulation model mice.1.3Impact on uterine blood flow in rabbitsThe experimental observation of blood stasis and hemostatic particles to animals in uterine blood flow. The results showed that the hemostatic particles remove high dose1dose after15min,30min,45min can significantly reduce the rabbit uterine blood f low (P<0.05,0.01) compared with the control group. The blood stasis hemostatic particles hemostasis and reduce uterine blood flow related.1.4The effect of Quyu hemostasis granules on blood stasis modle ratsThe acute blood stasis model was established to discuss the efftect of Quyu hemostasis granules on hemorheological indicators of blood stasis rats and to explore the role of "stasis". The results show that, compared with the model group, Quyu hemostasis granules had little effect of blood rheology parameters on blood stasis model rats. Quyu hemostasis granules middle dose had the trend to reduce whole blood viscosity of blood stasis model rat. Quyu hemostasis granules high dose could reduce the Plasma viscosity, erythrocyte aggregation index and elevated red blood cell deformability index of blood stasis model rat, but all had no significant statistically. Quyu hemostasis granules couldn’t improve the relevant indicators of blood stasis model rats, indicators the "stasis" is not obvious.Section2Mechanism of Quyu hemostasis granules in the treatment of ovulatory DUB2.1Quyu hemostasis granules on the content of uterine PGE2, PGF2α, t-PA and PAI-1in DUB rat modelThe experimental rat model of dysfunctional uterine bleeding, the immunohistochemical method observed t-PA, PAI-1expression in the endometrium, ELISA method for the determination of uterine PGE2, PGF2t-PA, PAI-1content. The results show that not conceive group, particles of blood stasis and stop bleeding, uterine PGE2content of the high-dose group were significantly higher (P<0.05), middle dose group uterine PGF2α were significantly increased (P<0.05), the high-dose group PGE2/PGF2α were significantly increased(P<0.05); blood stasis and hemostatic particles high dose group womb PAI-1were significantly reduced(P<0.05) in the high dose group t-PA/PAI-1ratio increased significantly(P<0.01). Blood stasis and stop bleeding the role of particle treatment of dysfunctional uterine bleeding and increased uterine PGF2α content, and reduce uterine fibrinolytic activity relationship.2.2Mechanism of Quyu hemostasis granules on rat coagulation functionThe experimental observation of a possible mechanism of blood stasis and hemostatic particles platelet aggregation and coagulation factors, and to explore its impact on coagulation function of normal rats and coagulation disorders. The results show that, compared with the control group, blood stasis and hemostatic particles is low, medium and high dose can be significantly increased the normal rat platelet aggregation rate(P<0.05), high doses can FIB content was significantly higher in normal rats (P<0.01); compared with the model group, blood stasis and hemostatic particles of low doses can improve coagulopathy rat ADP-induced platelet aggregation (P<0.05), low, medium and high dose can coagulopathy rats TT time significantly reduced (P<0.01), PT time was significantly shorter(P<0.01). The blood stasis hemostatic particles may affect the extrinsic coagulation pathway to lead to confrontation warfarin coagulopathy.2.3The effect of Quyu hemostasis granules on uterine contraction of rats.The uterine contraction were observed after duodenum administration on rats. The results show that, compared with the control group, Quyu hemostasis granules low dose could inhibit the uterine base pressure decrease after30-60min administration of rats, high doses could reduce the uterine contraction activity during the90-150min after administration (P<0.05). However, Quyu hemostasis granules has little effect on rat uterine contraction activity in general.In summary, this study discussed the effect and mechanism of Quyu hemostasis granules for ovulatory dysfunctional uterine bleeding. The results showed that Quyu hemostasis granules had significantly hemostasis and procoagulant effect, could successfully reduce the amount of bleeding blood in ovulatory DUB model rat. The mechanism may include:reduce uterine blood flow, increased the content of uterine vasoconstrictor active substances PGF2α; elevated plasma FIB level and the extrinsic coagulation pathway to promote blood clotting. |