金草片对子宫肌瘤模型大鼠子宫组织一氧化氮合酶表达的影响

目的:探讨金草片对子宫肌瘤模型大鼠子宫组织一氧化氮合酶(NOS)表达的影响,及该模型与临床发病机理的相关性。方法:以雌激素和雌、孕激素肌肉注射造成大鼠子宫肌瘤模型,测定子宫组织的总型NOS和诱导型NOS(iNOS)的水平;用放射配体结合分析法测定子宫组织雌激素受体(ER)水平;用放射免疫法测定血清雌二醇(E2)和孕酮(P)水平。结果:模型组大鼠子宫组织总型NOS和诱导型iNOS表达均明显增强,E2、ER和P水平升高;P水平与NOS表达相关,与iNOS表达不直接相关。金草片组可明显降低子宫组织NOSi、NOS和ER表达,降低血清E2和P水平,与模型组比较差异显著。结论:金草片可抑制子宫肌瘤模型大鼠子宫组织NOS表达,其作用可能是该品种治疗子宫肌瘤的作用机理之一。

植物性雌激素对子宫肌瘤模型大鼠血清中E_2、P及EGF的影响

目的观察植物性雌激素对子宫肌瘤模型大鼠雌二醇(E2)、孕激素(P)及表皮生长因子(Epidermal Growth Factor,EGF)的影响。方法采用Fujii的方法复制子宫肌瘤大鼠模型,并连续给予豆类植物性雌激素12周后观察各组大鼠血清中E2、P及EGF的含量。结果植物性雌激素能提高子宫肌瘤模型大鼠血清中E2、P及EGF的含量,且以高剂量组效果最显著(P<0.01)。结论植物性雌激素对子宫肌瘤模型大鼠具有加重的作用。

子宫肌瘤动物模型相关生物标记物的研究

目的:寻找与大鼠子宫肌瘤模型相关的生物标记物,探讨标志模型成功及药物有效性评价的动态和无损伤性指标。方法:采用基于核磁共振谱(NMR)的代谢组学方法,动态收集大鼠子宫肌瘤模型造模不同时间点的尿液,测定其NMR,并结合组织病理学检查,验证其生物标记物。结果:与空白组比较,在造模不同时间点,模型组大鼠尿液的代谢状态和代谢产物表型有显著性差异,其尿液中与模型相关的乙酸酯、牛磺酸、二甲胺和氧化三甲胺的NMR谱峰在造模后8周有显著改变;空白组、模型组和米非司酮组在主成分分析图上可明显分开,其中米非司酮组位于模型组和空白组之间;同时在造模不同时间点,子宫组织出现不同程度的病理改变。结论:NMR图谱中的谱峰变化能反映不同造模阶段的整体状态,其中乙酸酯、牛磺酸、二甲胺和氧化三甲胺的谱峰改变可作为子宫肌瘤大鼠模型的早期生物标记物及药物有效性评价的动态观察指标。

子宫肌瘤大鼠血浆的代谢组学研究

目的:研究子宫肌瘤模型大鼠造模过程中血浆代谢表型的动态变化及其与组织病理和生化指标的相关性,探讨标志模型成功及药物有效性评价的动态和无损伤性生物标记物指标。方法:于造模过程中4个不同时间点收集大鼠血浆,采用基于核磁共振谱(nuclear magnetic resonance,NMR)的代谢组学方法,测定其NMR,同时进行组织病理学检查和相关生化指标测定。结果:造模不同阶段模型组大鼠血浆的代谢谱与空白对照组比较均有显著差异,随着造模时间的延长,模型组大鼠血浆的代谢谱呈现出不同变化,其变化与子宫组织病理学和免疫组化指标改变相一致。结论:子宫肌瘤模型大鼠血浆代谢谱的谱峰变化能反映造模不同阶段动物的整体病理状态,并且该代谢谱的检测较病理检测便捷、无损伤,可作为子宫肌瘤大鼠模型的早期生物标记物性指标和药物有效性筛选的动态观测指标。

ATRA对大鼠子宫肌瘤发生、发展的影响

目的探讨全反式维A酸(ATRA)对雌孕激素诱导性子宫肌瘤大鼠模型子宫肌瘤发生、发展的影响。方法选取SPF级雌性Wistar大鼠60只,编号后采用随机数字表法分为空白组、模型组和ATRA组,每组20只。采用苯甲酸雌二醇对模型组和ATRA组进行肌肉注射[0.5 mg(kg·d),12周]、黄体酮肌注[5.9 mg(kg·d),12周],ATRA组于第10周起给予ATRA肌注(0.5 mg/d,2周)。分析比较各组大鼠子宫重量、子宫系数等指标,以及血清激素、维A酸受体α(RARα)、一氧化氮合酶(i NOS)的水平。结果模型组、ATRA组大鼠的子宫重量、子宫系数、左右宫角长度值、宫角最大值均显著高于空白组(P<0.05),ATRA组大鼠的子宫重量、子宫系数、左右宫角长度值、宫角最大值、宫颈长度值均显著小于模型组(P<0.05)。ATRA组大鼠的雌二醇(E2)、孕酮(P)、促黄体生成素(LH)值均显著小于模型组(P<0.05)。模型组、ATRA组大鼠的子宫组织RARɑ表达显著高于空白组(P<0.05),模型组大鼠i NOS表达显著高于空白组、ATRA组(P<0.05),ATRA组的子宫组织中i NOS表达显著高于空白组(P<0.05)。结论 ATRA可通过与RARɑ结合抑制NO的增加,调节激素水平,从而达到抑制子宫平滑肌细胞增殖的目的。

Effect of Lichong decoction on expression of Bcl-2 and Bcl-2-associated X protein mRNAs in hysteromyoma model rat

OBJECTIVE:To study on effects of Lichong decoction on expression of apoptosis-controlling genes,Bcl-2 and Bcl-2-associated X protein(Bax) mRNAs in hysteromyoma tissue of the hysteromyoma model rat.METHODS:Fifty Wistar female rats were randomly divided into a normal group,a model group,a Lichong decoction group,a Guizifuling capsule group and a Mifepristone group.The hysteromyoma rat model was established by intraperitoneal injection of exogenous estrin and progestogens.Pathological examination of uterine tissue,uterine coefficient and uterine transverse diameter were made under optic microscope and expressions of Bcl-2 and Bax mRNAs in uterine tissue in the groups were detected with real-time fluorescent quantitative polymerase chain reaction(PCR) technique.RESULTS:After treatment,under microscope it was found that in the Lichong decoction group myometrium thinned,muscle fiber slightly overgrowth or long and thin,regular arrangement,inserting phenomenon of inner circular muscle and external longitudinal muscle was occasionally or not seen in the Lichong decoction group.The uterine coefficient and the uterine transverse diameter significantly decreased(P<0.01),and Bcl-2 mRNA expression significantly decreased(P<0.01) and Bax mRNA expression significantly increased in hysteromyoma tissue(P<0.01) in the Lichong decoction group as compared with the model group.CONCLUSION:Therapeutic effects of Lichong decoction on hysteromyoma is related with decrease of Bcl-2 mRNA expression and increase of Bax mRNA expression.

Effect of Lichong Decoction on expression of IGF-I and proliferating cell nuclear antigen mRNA in rat model of uterine leiomyoma

OBJECTIVE:To study the effect of Lichong Decoction(Lichong Decoction for strengthening anti-pathogenic Qi and eliminating blood stasis) on the expression of insulin-like growth factor-I(IGF-I) and proliferating cell nuclear antigen(PCNA) mRNA in a rat model of uterine leiomyoma.METHODS:Fifty female Wistar rats were randomized into a normal control group,model group,Lichong Decoction group,Guizhifuling Capsule(Capsule containing Cassia Twig and Poria) group,and Mifepristone group.The uterine leiomyoma model was established by peritoneal injections of exogenous estrogen and progesterone hormone.The ultrastructural changes in cells of rat uterine tissues were observed with transmission electron microscopy,and the expression of IGF-I and PCNA mRNA was detected by real-time fluorescent quantitative PCR.RESULTS:Following treatment,cells in the Lichong Decoction group appeared to be arranged normally,the cellular morphology were almost in a normal state,hyperplasia and hypertrophy of the chondriosome was reduced,collagen fibers were arranged in a regular manner,without obvious hyperplasia,and the expression of IGF-I and PCNA mRNA was significantly decreased compared with the model group(P<0.01).CONCLUSIONS:The effect of Lichong Decoction on uterine leiomyoma is related to its function in reducing the expression of IGF-I and PCNA mRNA.