| Objective:1. The clinical symptoms in patients with symptomatic uterine leiomyomas (UL) were collected and organized, then to analyze the distributive regulation of TCM, the syndrome influential factors and the eating habits on UL, so as to guide the clinical application, establish foundation of diagnostic standardization on syndromes and Chinese medicine treatment.2. Based on the pathogenesis of uterine leiomyoma that were hormone dependent tumors, to compare the diffierence between the two constructing methods rat model with uterine leiomyoma, and to explore the method of the rat model of uterine leiomyoma, to provide the basis for further experiments; and to test the blood viscosity and analyze the hemorheological of the model rats.3. To study the effect of Juli Sanjie Pills and Decoction on the rat model of UL induced by estrogen and progesterone, then to observe the general morphology of the rats’uterus, the viscosity of whole blood, inerleukin-6(IL-6) and tumor necrosis factor-α (TNF-α) in the rats’serum, the expression of estrogen receptor (ER), progesterone receptor (PR) and epidermic growth factor receptor (EGFR). And to explore the treatment mechanisms of Juli Sanjie Pills on uterine leiomyoma.Methods:1. This study collected the basic information and the four diagnostic data through the observation of the in-patients and out-patients from the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from January2010to February2012, then analyzed and summarized the distribution of each factors:their age, duration, syndrome distribution, eating habits and the incidence of the common symptoms.2.48healthy female SD rats were randomly divided into short-term control group, short-term model group, long-term control group and long-term model group. The rats of short-term model group were given a daily intraperitoneal injection of estradiol benzoate injection with the dose of0.05mg/100g, and after25days changed for progesterone injection (0.4mg/100g) once daily for5days; The rats of short-term control group were given a daily intraperitoneal injection of peanut oil for30days. The rats of long-term model group were given an intramuscular injection of estradiol benzoate injection with the dose of0.05mg/100g,3times/week.12weeks later, they were given together progesterone injection0.5mg/100g,2times/week for4weeks. The rats of long-term control group were gave an intramuscular injection of peanut oil in the same time.3.100healthy female SD rats were randomly divided into10groups (n=10):group A, group B, group C, group D, group E, group F, group G, group H, group I, group J. In addition to group A, the rats were given an intramuscular injection of estradiol benzoate injection0.05mg/100g,3times/week.12weeks later, they were given together progesterone injection0.5mg/100g,2times/week for4weeks. The rats of group A were given an intramuscular injection of peanut oil in the same time. From the fifth weeks, except the rats of group A and group B, the rest rats were fed with corresponding drugs until the16th weeks.Results:1.505cases with final diagnosis of uterine leiomyoma had been collected, whose average age was37.66±7.12.>36-≤40years old have a higher prevalence, followed by>30-≤35years old and>40-≤45years old;30-50years old in a total incidence of79.41%. The number of under the age of25was8, with the incidence of1.58%, which explained that uterine leiomyoma had young tendency. The result of dietary survey of178cases with uterine leiomyoma showed that most patients addicted to meat, accounted for53.37%, while the patients with vegetarian habits accounted for less proportion, a total of4.49%. The difference of diet composition have statistical significance(P<0.05). Abdominal mass and large volume of menses were the common symptoms, whose occurrence rate respectively was77.62%and33.66%respectively. The common tongue proper, the tongue coating and pulse was dark pale tongue, thin and white tongue coating and string and thin pulse, accounting for30.10%,61.39%,32.08%respectively. The most common syndrome was syndrome of Qi stagnation and blood stasis, whice accounted for45.5%of the total cases, and followed by syndrome of phlegm and blood stasis and blood stasis and kidney deficiency, accounted for17.4%and14.3%respectively. The correlation between patients’age, gravidity, parity, dietary habits and syndromes had significant difference (P<0.05or P<0.01). And there was no correlation for patients’course of disease, the number of abortion and syndrome distribution.2. The uterus volume, uterus coefficient and uterine muscle’s thickness of rats from short-term model group and long-term model group increased after long-time and short-time modeled, and the long-term model group increased significantly. The difference between the long-term model group and the long-term control group was statistically significant (P<0.05or P<0.01). HE staining showed the the uterine muscles were disorde, some looked like palisade. The ovarians’coefficient of rats from short-term model group and long-term model group was lowered significantly (P<0.05or P<0.01). The whole blood viscosity at high shear, middle shear and lower shear of the rats from long-term model group was decreased significantly compared with the long-term control group. The whole blood viscosity was reduced too, but there was no difference between the short-term control group (P>0.05). The rat’plasma viscosity was increased in short-term model group and long-term model group, but there was no difference compared with the short-term control group and the long-term control group (P>0.05).3. Uterine morphology:The uterus vertical diameter and transverse diameter over the cervical, the width of left cornua uteri, the width of right cornua uteri, uterus coefficient, uterine muscle’s thickness of rats of group B increased significantly (P<0.05or P<0.01). And the ovarians’coefficient of rats from group B decreased significantly (P<0.05). After treated by medicine, the uterus coefficient, uterus volume and quota decreased, and the ovarians’coefficient increased. The uterus quota of rats from group C decreased significantly, but the ovarians’coefficient didn’t increase. The uterus quota of rats from group D decreased too, the group F, H, I, J decreased significantly, and the group I decreased most significantly; the difference was significantly compared with group B (P<0.05). The ovarians’coefficient of rats from group D, F and J increased significantly compared with group B (P<0.05or P<0.01). The uterine muscle’s thickness of rats from D, F, H, I and group J increased significantly compared with group B (P<0.05or P<0.01).4. Blood viscosity:The whole blood viscosity at high shear, middle shear and lower shear of the rats from group B was decreased extremely significantly compared with group A (P<0.01). The plasma viscosity of rats from group B was increased, but there was no significant difference compared with the group A (P>0.05). After treated by medicine, The whole blood viscosity was changed. The whole blood viscosity of the rats from group I was increased significantly and the plasma viscosity of rats from group B was decreased significantly compared with group B (P<0.05or P<0.01). The change of group C and D was not significant.5. IL-6:The serum IL-6of group B was decreased significantly compared with group A (P<0.05). After treated by medicine, the serum IL-6increased except group C. The serum IL-6of group H and I was increased significantly compared with group B (P<0.05).6. TNF-a:The serum TNF-a of group B was increased extremely significantly compared with group A (P<0.01). After treated by medicine, the serum TNF-a decreased extremely significantly compared with group B (P<0.01) and group F, H, I and J decreased more significantly.7. ER:The ER expression in myometrial of group B increased significantly compared with group A (P<0.05). ER expression in myometrial of I group decreased significantly compared with group B (P<0.05). ER expression in myometrial of group C, D, F, H and J decreased too, but the difference was not significant compared with group B (P>0.05).8. PR:The PR expression in myometrial of group B increased significantly compared with group A (P<0.05). After treated by medicine, The PR expression in myometrial decreased, group C and I decreased significantly compared with group B (P<0.05). PR expression in myometrial of group D, F, H and J decreased too, but the difference was not significant compared with group B (P>0.05).9. EGFR:The EGFR expression in myometrial of group B increased significantly compared with group A (P<0.05). After treated by medicine, The EGFR expression in myometrial decreased, group I decreased significantly compared with group B (P<0.05). EGFR expression in myometrial of group C and J decreased more than group D and F, but the difference was not significant compared with group B (P>0.05).Conclution:1. High prevalence in patients with uterine leiomyoma was from36to40years old. Addicted to meat might damage the function of spleen and kidney, resulting in phlegm stasis, blood stasis and kidney deficiency, which increased the risk of uterine leiomyoma. Abdominal mass and large volume mense were the common symptoms. The common tongue proper, the tongue coating and pulse respectively was dark pale tongue, thin and white tongue coating and string and thin pulse. The most common syndrome was syndrome of Qi stagnation and blood stasis. And followed by syndrome of phlegm and blood stasis, blood stasis and kidney deficiency. With the growth of the age, the increase of the number of abortion and syndrome, the rate of blood stasis and kidney deficiency increased gradually.2. The method of Estrogen and progesterone load with long time could successfully establish rat model of uterine leiomyoma. The method could be used as the ideal model of uterine leiomyoma animal experiments.3. Juli Sanjie Pills and Decoction could significantly inhibit hyperplasia of uterine smooth muscle and promote the recovery of ovarian. The comprehensive effect of Juli Sanjie Pills and Decoction was better than mifepristone and Guizhifuling capsule and it was a good approach in treating uterine leiomyoma. The mechanism of Juli Sanjie Pills was probably by reducing ER, PR and EGFR, inhibiting hyperplasia of uterine smooth muscle, modulating the immunity, inhibitting inflammatory response, enhancing the effect of body killing tumor cells, promoting the formation of blood cells and ameliorating anemia and blood stasis state. |
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