| BackgroundPolycystic ovarian syndrome (PCOS) is one of most common endocrine disease, the syndrome encompasses a broader spectrum of signs and symptoms, such as elevated serum hyperandrogenism and insulin resistance. PCOS patients with follicular development stagnation, and no mature follicles, so the key treatment to PCOS patients is to promoting follicles development, and inducing ovulation. For PCOS anovulatory patients, the clinical treatment of ovulation is clomiphene citrate(CC), the ovulation rate was80%, but the pregnancy rate is only30%--40%. Clomiphene can lead to endometrial dysplasia, cervical mucus quantity change and the luteinized unruptured follicle syndrome and affect the pregnancy rate. Because of chronic anovulation, estradiol and progesterone secretion is inharmonious, the implantation of endometrium and cell survival associated with abnormal expression, resulting in decrease of endometrial receptivity. Therefore, how to correct the reduced endometrial receptivity in PCOS patients with endocrine disorders and application of ovulation induction therapy, is a big challenge for modern medicine.The famous professor Li Liyun of Guangdong Province Hospital Of Traditional Chinese Medical, created Shen-Qi capsule. She basis the previous experience with clinical experience, put forward the traditional chinese medical etiology and pathogenesis of kidney deficiency, blood stasis and phlegm as a standard, with kidney and phlegm and activating blood method, adjustment of gonadal function, maintenance of luteal function, thus improving improve the receptivity of endometrium, to achieve better clinical efficacy. Objective1. To investigate the expression of Shen-Qi capsule on PCO in rat’s endometrium integrin αvβ3, LIF, glycodelin, improve the expression of endometrial receptivity, to clarify the possible molecular mechanism of its efficacy, to provide the experimental basis for the clinical treatment of PCOS based on infertility.2. By transvaginal color Doppler flow imaging before and after the treatment of uterine artery pulsatility index (PI) and resistance index (RI), ovarian stromal artery pulsatility index (PI) and resistance index (RI) hemodynamic changes, to evaluate the clinical effect of Shen-Qi capsule improvement PCOS in patients with endometrial receptivity, and explore its possible mechanisms of action, and provide a scientific basis for further clinical application and promotion.Methods1. Experimental study:PCO rat model was experimentally induced by the24-day-old female rats by subcutaneous injection of oilsolution of dehydroepiandrosterone (DHEA) for continuous20days. The rats with PCO were randomly divided into control group, model group, Shen-Qi treating group, clomiphene treating group, Shen-Qi and clomiphene treating group. The treatments were given for14days since80days after birth. The serum testosterone and fasting insulin levels were obtained after treatment. We observed the change of uterine and ovarian organ coefficient, endometrium and ovarian morphology. The expressions of integrin αvβ3, LIF and glycodelin, to explore the possible mechanism of Shen-Qi capsule.2. Clinical research:by means of randomized controlled clinical research methods, Guangdong Province Hospital Of Traditional Chinese Medical, from2012.2-2012.12, They are divided divided into two groups by1:1randomly, the control group including23cases, and treatment group including23cases, clomiphene is given to the control group, and at the same time clomiphene and Shen-Qi capsule are given to treatment group. Two groups are inspected by using Chinese medicine syndromes graded tables, the hemodynamic monitoring of uterus and ovary, and other observe variable index, such as sex hormones, blood glucose, insulin, blood lipid, using PASW Statistics17.0statistical software to establish a database and statistical analysis. Results1. Results of experimental study:(1) The comparison of control group and the successed animal model group: the latter surpass the former in these mean observe index, such as weight, serum testosterone and fasting insulin levels, the differences were statistically significant (P<0.05).(2) The difference of each group after treatment of drug intervention:①) Weight:The treatments were given for14days, Shen-Qi treating group, clomiphene treating group and Shen-Qi and clomiphene treating group rats’ weight compared with model group tended to decrease, which is in the Shen-Qi and clomiphene treating group decreased more obviously, but the differences were not statistically significant (P>0.05).②Comparison of testosterone, fasting insulin levels:model group serum T got higher level than control group(P<0.01); compared with model group, the three treating groups serum T levels were decreased to some extent, the differences were statistically significant (P<0.01), But from the comparison of the mean, the first is Shen-Qi treating group, the second is clomiphene treating group, the lowest is Shen-Qi and clomiphene treating group. There is no distinct statistcal differences between Shen-Qi treating group and clomiphene treating group(P>0.05). The FINS level of each group:compared with control group, model group got higher the serum T level (P<0.01); Shen-Qi treating group, clomiphene treating group, Shen-Qi and clomiphene treating group after therapy, the serum FINS level were compared with model group decreased(P<0.01). The serum FINS levels were similar between these three groups, the differences were not statistically significant (P>0.05).③Comparison of uterine and ovarian organ coefficient:there is distinct statistical differences between control group and model group ovarian organ coefficient (P<0.01); after treatment, compared with model group, clomiphene treating group and Shen-Qi and clomiphene treating group decreased ovarian organ coefficient, the differences were statistically significant(P<0.05) there is no distinct statistical differences between Shen-Qi treating group and model group(P>0.05); compared with control group, there is lower uterine organ coefficient model group(P<0.05);compared with model group, there is no significant uterine organ coefficient statistical among Shen-Qi treating group、clomiphene treating group and Shen-Qi and clomiphene treating group(P >0.05). compared with model group, Shen-Qi treating group, Shen-Qi and clomiphene treating group uterine organ coefficient increased, uterine organ coefficient in clomiphene treating group is lower than that of Shen-Qi treating group and Shen-Qi and clomiphene treating group, the difference was statistically significant (P<0.05).④The results of immunohistochemistry:compared with the control group, model group endometrial the expression of integrin αvβ3, LIF, glycodelin decreased(P<0.01). Compared with model group, clomiphene treating group endometrium integrin avP3, LIF, glycodelin decreased significantly, the differences were statistically significant (P<0.05), while Shen-Qi treating group, Shen-Qi and clomiphene treating group can upregulate the expression (P<0.01), and Shen-Qi and clomiphene treating group was closer to the expression of control group.2. Results of Clinical study:(1) Body mass index and waist-hip ratio:the treatment group (Shen-Qi and clomiphene treating group) and control group (clomiphene treating group) with body weight, BMI and waist-hip ratio levels than before treatment was significantly decreased, the differences were statistically significant (P <0.05).(2) Color Doppler flow imaging:the treatment group and the control group of patients with ovarian volume after treatment than before treatment, there is no statistical difference (P>0.05); After treatment, the treatment group of uterine artery PI, left ovarian stromal artery PI and right ovarian stromal artery PI than before treatment was signicantly decreased, the differences were statistically significance(P<0.01). After treatment, the treatment group of uterine artery RI, the left ovarian stromal artery RI and right ovarian stromal artery RI than before treatment was signicantly decreased, the differences were statistically significance (P<0.05). While the control group of uterine artery and ovarian stromal artery PI、RI after treatment than before treatment, there is no statistical difference(P>0.05).(3)Blood glucose and insulin levels:after treatment, the treatment group of2h-PG decreased, the differences were statistically significant (P<0.05);2h-INS than before treatment decreased, the differences were statistically significant(P<0.01). After treatment, HOMA-IR decreased, the differences were statistically significant (P<0.05). The control group of patients with blood glucose, insulin after treatment than before treatment, there was no statistical difference(P>0.05).(4) Serum sex hormones levels:after treatment, the treatment group of patients with LH, LH/FSH and T before treatment were improved in varying degrees, LH and T levels reduced than before treatment, the differences were statistically significant (P<0.01); LH/FSH reduced than before treatment, the differences were statistically signif icant(P<0.05). After treatment, the control group compared with before treatment T level has a tendency to decreased, but there was no statistically significant difference (P>0.05), serum LH level was lower (P<0.05). after treatment, serum FSH, E2^P and PRL before treatment, there was no statistically significant difference (P>0.05).(5) Blood lipids:the treatment group and the control group with TG, TC, HDL-C, LDL-C, ApoAl, ApoB, ApoAl/ApoB after treatment than before treatment, there is no statistical difference (P>0.05).(6) TCM syndrome:the treatment group and the control group both can improve the quantitative scores of TCM symptoms of PCOS patients (P<0.01).Conelusion1. Experimental study:(1) The PCO animal model of SD juvenile female rats established induced by DHEA, the morphology changes and endocrine alterations are similar to clinical PCOS patients, is an ideal animal model of PCOS.(2) The phenomenon of low expression of PCO rats use clomiphene ovulation and endometrial integrin avβ3、LIF、glycodelin, may be related to endometrial receptivity damage.(3) Shen-Qi capsule can improve the PCO rat endometrial the expression of integrin αvβ3、LIF、glycodelin, improve the endometrial receptivity.2. Clinical research:(1) Endometrial thickness and morphology of color Doppler flow imaging, uterine and ovarian stromal artery blood flow can serve as an indicator of pinopode, for evaluation of endometrial receptivity.(2) The clinical application of clomiphene in ovulation induction cycle plus Shen-Qi capsule, play a synergistic effect, in the improvement in patients with Endometrial thickness and morphology, adjust the uterine artery and ovarian stromal artery blood flow were significantly better than clomiphene therapy. Prompt Shen-Qi capsule can regulate the endocrine function of patients with PCOS, correct clomiphene negative effects on the endometrium, improve endometrial receptivity. |
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