【作者】 王雯斌；

【导师】 杨秀萍；

【作者基本信息】 首都师范大学 ， 细胞生物学， 2006， 硕士

【摘要】 目的：探讨妇科常用药川芎嗪对于小鼠早期妊娠的影响及其作用机理，从而评价其对于早期妊娠的安全性。 方法：从妊娠第1天开始，将3个浓度（10mg／天、2mg／天、0.4mg／天）的盐酸川芎嗪及酸性生理盐水对妊娠小鼠进行灌胃6天，于第7天处死小鼠取血制备血清，利用放射免疫法测定血清内孕酮（Progesterone，P）、睾酮（Testosterone，T）及雌二醇（Estradiol，E₂）浓度；取子宫及卵巢组织，利用免疫组织化学半定量测定卵巢内促黄体激素受体（Luteinizing Hormone Receptor，LHR）／绒毛膜促性腺激素受体（Chorionic Gonadotropin Receptor，CGR），子宫着床部位孕酮受体（Progesterone Receptor，PR）表达量；取妊娠10天黄体细胞，加入不同浓度川芎嗪，在有／无人绒毛膜促性腺激素（human Chorionic Gonadotropin，hCG）的情况下进行体外培养，测定细胞培养液中孕酮浓度；取足月分娩小鼠计数并测量其分娩的仔鼠数量、窝重、仔鼠体重、后肢长、尾长、头长、全长等指标。 结果：各浓度组孕鼠血清中雌二醇浓度均高于对照组（P＜0.001），高浓度组（10mg／天）孕酮及雌、孕激素比值（E₂／P）均显著高于对照组（P＜0.05），而各组间睾酮无显著差异（P＞0.05）。体外培养妊娠小鼠卵巢细胞在1μg／ml-100μg／ml的川芎嗪作用下分泌的孕酮显著高于对照组（P＜0.05）。免疫组化结果表明，不同浓度的川芎嗪均能显著增强卵巢中LHR／CGR的表达，其表达量随着川芎嗪浓度的增加而增加（P＜0.05，P＜0.001，P＜0.001），同时显著减弱子宫中PR的表达，其表达量随着川芎嗪浓度的增加而降低（P＞0.05，P＜0.01，P＜0.001）。高浓度组妊娠小鼠的分娩率、每窝仔数和窝重均显著低于对照组，而仔鼠体重则显著高于对照组（P＜0.05）。低浓度组（0.4mg／天）所产仔鼠尾长、头长、后肢长均明显长于与对照组（P＜0.05）。 结论：盐酸川芎嗪可以单独并通过提高卵巢内LHR／CGR的表达水平而提高妊娠小鼠血清中P与E₂浓度，干扰生殖内分泌平衡，并降低子宫组织内胚胎着床部位PR的表达量，从而不利于妊娠，并且对所产仔鼠的体格有一定影响。更多还原

【Abstract】 Objective To investigate the effect of Ligustrazine Hydrocholride as a drug contraindicated on estrogen and progesterone in mice serum as well as progesterone receptor （PR） and luteinizing hormone receptor/chorionic gonadotrophin receptor （LHR/CGR） in mice luteal cell during pregnancy to evaluate the safty with Ligustrazine Hydrochloride.METHODS The pregnant mice were treated intragastrically with different concentrations of Ligustrazine Hydrochloride （10mg/d, 2mg/d or 0.4mg/d） for six days from the first day of pregnantcy. The control group was treated with acidic saline. The concentrations of progesterone and estradiol in serum were measured by RIA. Immunohistochemical staining was used to detect the quantity of LHR/CGR, PR respectively from ovary and uterus, respectively. The quantity of embryo was recorded. The mouse ovarian cells at midpregnacy were cultured in virto under different concentrations of Ligustrazine Hydrochloride with/without hCG. RESULTS Compared with the control group, the level of estradiol distinctly increased in serum of lOmg/d, 2mg/d and 0.4mg/d group. The ratio of E₂/P and the concentration of progesterone remarkably increased. The concentration of progesterone in the supernatant of cultured ovarian cells under 1μg/ml-100μg/ml was remarkably augmented when compared with control group. The data also showed that the expression of LHR/CGR was enhanced while the expression of PR was inhibited by Ligustrazine Hydrochloride. The number of embryo significantly decreased in the group of 10mg. The parturition rate, the number of litter, the weight of litter were also decreased when compared with control group, but the weight of individual mouse was increased. The length of tail, head, limbs were longer than those of in control group. CONCLUSION The Ligustrazine Hydrochloride has a disadvantageous effect on mouse pregnancy probably by increasing the concentration of P, E₂ and decreasing the expression of PR, but didn’t have any significant influence on litters.更多还原