| ObjectivesTo discuss the pathogenesis of threatened abortion vaginal bleeding, analyze the the influence of clotting function, blood viscosity, serum hormone level and uterine artery blood flow index on threatened abortion vaginal bleeding and compare the data before and after medication, To Investigate the curative effect of traditional Chinese medicine compound Zi Shen Yu Tai Wan(ZSYTW) for the hemostatic effect of vaginal bleeding symptoms, as well as anti-abortion effect for threatened abortion patients. And establish model rats of threatened abortion vaginal bleeding, Compound ZSYTW, with positive clinical effect for Reinforcing the Kidney and Invigorating the Spleen, and Anti-abortion and Nourish-blood, was selected as the research drug, and indexes including rat’s general situation, E2and P level, blood coagulation function, blood rheology, uterine contractions in vivo experiment were tested as evaluation indexes. Study the whole preparation of ZSYTW and test for each single hemostatic ingredient, to look for effective drug for hemostatic and anti-abortion function by verification test of drug effect, forming a standard process of the establishment of threatened abortion vaginal bleeding rats model, providing fundamental information about pharmacology of ZSYTW. Methodology1. Clinical study (Clinical Study of Treatment of Pregnancy Threatened Abortion by Zi Shen Yu Tai Wan):Totally60patients with threatened abortion were selected as the research objects based on the inclusion and exclusion criteria, according to the random number table method, the patients are divided into TCM treatment group and western medicine control group,30cases in each group. During the treatment, researchers will complete the clinical observation table on the initial and regular visit of patients, and follow-up the patients. TMC group will take ZSYTW, while the western medicine control group to will take progesterone, are all treated for one course, and evaluate ZSYTW s curative effect on Kidney-deficiency type of threatened abortion, impact on the level of serum HCG, P and E2, on blood coagulation function, blood rheology, assess the function in the observation of threatened abortion treatment effect of following indexes:dynamic monitoring serum HCG, P and E2level, blood clotting index, blood rheology indexes and ultrasound observed uterine artery blood flow resistance index (RI), and pulse index (PI)2. Experimental study (Experimental Study of Creation of Threatened Abortion Rats Model and Traditional Chinese Medicine Intervention):70pregnant rats were randomly divided into7groups:normal control group, model control group, positive control group, ZSYTW group (group A), Group of Jiao Lu Ai(JLA)(group B), Group of Qu Jiao Lu Ai(Q JLA)(group C), E Jiao group (group D). From the first day of pregnancy, rats of each group were given gastric perfusion at9am every day, normal and model control rats were given normal saline by gavage, and positive group rats were given dydrogesterone aqueous solution; the rest of the group were given corresponding TMC. After pregnancy for10days, except the normal control group, each group of rats were given3.75mg/kg solution of mifepristone (RU486), forming threatened abortion vaginal bleeding model, at the same time,100mg cotton plug was put into the rats’vagina. After24hours, the plugs were taken out, weighed and sealed, waiting for the test of vaginal haemorrhage quantity, Eyeball blood method was applied for the blood sampling after anesthesia by5%pentobarbital.1.5ml serum from whole blood was tested for the content of E2, P, TXB2,6-k-PGF1α,6ml of anticoagulant tube with whole blood was detected of the blood coagulation function and blood rheology. Laparotomy was conducted immediately after the blood was taken, and exposed the uterus, doing the uterine contractions in vivo experiment for40minutes, record the curve chart. The uterus were took and weighed, and then calculated the embryo number and observe uterine hemorrhage situation, specimens were preserved with formalin. ResuIts1. Clinical study1.1Comparison of clinical curative effect and TCM symptom score before and after treatment in patients indicated that ZSYTW has a satisfactory clinical effect for the treatment of this disease, the effective rate was 56.67%, total effective rate was100%, there was no significant difference compared between the two groups (P>0.05); TCM syndromes effective rate was56.67%, total effective rate was100%, the comparison between the groups indicated no significant difference (P>0.05). After treatment, TCM syndrome integral was reduced significantly (P<0.01), there was no significant difference compared between the two methods(P>0.05).1.2Comparison of indexes before and after treatment in patients indicated that:ZSYTW could improve patients’ β-HCG, P and E2level in serum, comparison before and after treatment of the treatment group had significant difference (P<0.01), there was no significant difference between two groups (P>0.05); ZSYTW could decrease whole blood viscosity, improve the early state of high coagulation, Whole blood high shear viscosity value of the treatment group were significantly different before and after treatment (P<0.01), there was no significant difference between between two groups (P>0.05); ZSYTW can prolong PT, reduce the amount of Fbg and D-2polymers, improve the state of high coagulation and pre-thrombotic, these Indexes of treatment group had significant difference compared between before and after treatment (P<0.05), there was no significant difference between the two groups (P>0.05); ZSYTW can reduce the uterine artery blood flow resistance index (RI) and pulse index (PI), improve uterine placenta perfusion status, RI&PI of treatment group had significant difference compared between before and after treatment (P<0.05), there was no significant difference between the two groups (P>0.05);2. Experimental study2.1Pregnant mice are in good status, with smooth hair color, flexible reaction, growing steadily weight, good appetite, defecate is normal. No adverse reactions during drug delivery. After dissection, it was observed in the normal group that uterus was bright pink, had nodular enlargement, well developed, clear boundaries between embryo, peripheral blood supply is rich, the embryo was intact; While in the Model group of mice, there were different degree of blood stasis, and visible enlarged nodules, fair development, the embryo number has no obvious decrease or missing, boundaries between embryo is comparatively obvious, the embryo was intact; The rest of the6groups of mice in the uterus were observed enlarged nodules, no difference of embryo numbers between the groups; Embryos of Group B, group C, group D had obvious blood stasis;pregnant mice of Positive group and the group A have blood stasis in uterus decreased significantly compared with model group.2.2Vaginal haemorrhage amount of model group was significant different from normal group (P<0.01); The vaginal haemorrhage amount of Positive group and B group compared with model group had extremely significant difference (P<0.01); Group A and group D compared with model group, had significant difference (P<0.05); Vaginal haemorrhage amount of Group A, group B, group C and group D compared with positive group had no significant difference (P>0.05); Vaginal haemorrhage amount of Group A had no significant difference compared with group B, C and D group (P>0.05).2.3For the serum E2Level, there was a very significant difference for Model group compared with the normal group (P<0.01). Group A and group B was significantly different from model group (P<0.05)., although there is no significant difference when Positive group, group C and group D compared with model group (P>0.05), but its E2levels were obviously higher than the model group E2level. For the comparison of serum P level, Model group had an extremely significant difference compared with normal group (P<0.01);, there was a very significant difference for positive group compared with model group (P<0.01); Group A and group B had significant difference compared with model group (P<0.05). Group C had no significant difference compared with model group (P>0.05), but significantly higher than the model group; Group A and group B had no significant difference compared with positive group (P>0.05); Group C and group D were significantly different from the positive group (P<0.05).2.4The test results of TXB2levels were as following, Model group had significant difference compared with the normal group (P<0.05); Positive group, group A and group B, C and D group had no significant difference compared with the normal group(P>0.05); Positive group, roup A and group C had significant difference compared with model group (P<0.05). Group B and group D had no significant difference compared with model group(P>0.05), but TXB2level of group B was lower than that of model group; Group A and group B had no significant difference compared with positive group (P>0.05); Group C and group D had significant difference compared with positive group (P<0.05). The test results of6-K-PGF1α levels were as following, The model group had no significant difference compared with the normal group (P>0.05), but the model group was obviously lower than normal group; Positive group, group A and group B, C and D group had no significant difference compared with model group (P>0.05), except for the group B and group C, other groups were significantly higher than that of model group, the level of group D was close to that of normal group. The test results of6-K-PGF1α levels were as following, Model group had extreme significant difference compared with the normal group (P<0.01); Positive group, group A and group B, C and D group had no significant difference compared with model group (P>0.05), but except group D, Levels of TXB2/6-K-PGF1α of other groups were all lower than that of model group, positive group and the group A were lower than that of model group.2.5The test results of PT levels were as following, model group slightly lower than normal group, but had no significant difference(P>0.05), Group A had extremely significant difference compared with model group(P<0.01), Positive group, group B, C and D groups are higher than that of model group, but had no significant difference (P>0.05). The test results of APTT levels were as following, The model group had extreme significant difference compared with the normal group (P<0.01); Positive group and the group A had extreme significant difference compared with model group (P<0.01). Group B, C and D group had significant difference compared with model group (P<0.05). The test results of Fbg value were as following, model had extreme significant difference compared with normal group (P<0.01); Positive group had extreme significant difference compared with model group (P<0.01); Group B, C and D group had significant difference compared with model group (P<0.05).2.6The test results of Fbg value were as following, Model group had no significant difference compared with the normal group (P>0.05); Positive groups, group A and group B and group D had no significant difference compared with model group(P>0.05). The plasma viscosity of Group C had significant difference compared with model group (P<0.05). The test results of whole-blood viscosity at medium shear value were as following, model group had no significant difference compared with the normal group (P>0.05), but obviously higher than normal group; group A had extreme significant difference compared with model group (P<0.01); Positive group, group B, group C and group D were slightly lower than the model group, but had no significant difference compared with model group (P>0.05). The test results of whole-blood viscosity at low shear value were as following, model group had extreme significant difference compared with normal group (P<0.01);Positive group and group had significant difference compared with model group (P<0.05); Group B, C and D group were lower than the model group, but had no significant difference (P>0.05).2.7The test results of uterine contraction frequency were as following, model group had extreme significant difference compared with normal group (P<0.01); Positive group had extreme significant difference compared with model group (P<0.01); Group A and group C had significant difference compared with model group (P<0.05); Group B and group D were slightly lower than the model group, but had no significant difference(P>0.05). The test results of uterine contraction strength were as following, model group had extremely significant difference compared with normal group (P<0.01); Positive group and the group A had extremely significant difference compared with model group (P<0.01); Group B and group C had significant difference compared with model group (P<0.05); Group D was slightly lower than the model group model group, but had no significant difference (P>0.05). Conelusion1. ZSYTW and dydrogesterone tablet on the treatment of Kidney-deficiency type of threatened abortion, to improve TCM symptoms of kidney deficiency, increase serum β-HCG, P, E2levels, decrease whole blood viscosity, prolong PT time, reduce the amount of Fbg and D-2polymers, reduce the uterine artery blood flow resistance has the similar curative effect.2. In the dynamic monitoring treatment of threatened abortion patients, the change of PT, Fbg and D-2polymers, as well as the uterine spiral artery blood flow resistance index (RI), pulse index (PI) under ultrasonic Doppler monitoring can be used as indexes for curative effect evaluation and prognostic judgement.3.This experiment successfully established model rats of threatened abortion vaginal bleeding, high simulation for clinical threatened abortion patients with vaginal bleeding. This study summarized professor Luo Songping’s kidney deficiency-corpus luteum restrain (combination of disease and syndrome) abortion model, based on which to establish the SOP of threatened abortion vaginal hemorrhage model in rats.4. Threatened abortion model rats showed following characteristics, P and E2level were reduced, PT and APTT were shortened, Fbg, whole blood viscosity, and TXB2levels, as well as the ratio of TXB2/6-K-PGF1a were increased, and contractions and strength also increased, the series of characteristics is identical with clinical manifestations. These features indicates that threatened abortion is related to the corpus luteum insufficiency, high adhesion and high coagulation state of blood, abnormal uterine contraction. This is the first comprehensive proposed pathogenesis of threatened abortion, providing reference index from different viewpoints for the clinical treatment of threatened abortion.5. The intervention of ZSYTW on the threatened abortion model of rats indicated that it has the similar function on the treatment of hemostasis and anti-abortion of threatened abortion compared with Dydrogesterone. The mechanism may be through the increase of E2and P content, in order to maintain the process of pregnancy; on the other hand, by reducing TXB2, and increasing the content of6-Keto-PGFl a to correct the imbalance in the body of the two indexes, to improve uterine placenta blood circulation so that thrombosis could be inhibited, to improve the uterus high coagulation and pre-thrombosis status, in order to ensure the continue of pregnancy; and by reducing blood viscosity and prolonging the clotting time, reducing the Fbg levels, to further improve the whole body blood high adhesion high coagulation status, thereby to achieve the purpose of treatment of threatened abortion.6. In terms of hemostasis, Group of JLA is significantly better than ZSYTW group and i group; Hemostatic effect of E Jiao is slightly lower than Group of JLA, but obviously better compared with Group of Q JLA. Indicates that hemostatic effect of ZSYTW is mainly achieved through Lu Jiao Shuang, Ai Ye, E Jiao. |
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