摘要
目的研究来曲唑治疗大鼠子宫内膜异位症的作用机制。方法采用子宫内膜自体移植法进行子宫内膜异位症建模,2015年3月,选择30只建模成功的大鼠,根据随机数字表法分为来曲唑组和对照组,各15只。曲唑组大鼠每日给药来曲唑灌胃,给药剂量为0.26 mg/kg,1次/d;对照组灌胃等体积的0.9%Na Cl注射液。采用免疫组织化学法对异位病灶组织中细胞间黏附因子(ICAM-1)、基质金属蛋白酶9(MMP-9)、血管内皮生长因子(VEGF)的表达情况。逆转录聚合酶链式反应(RT-PCR)检测病灶中白细胞介素6(IL-6)m RNA、肿瘤因子(TNF)αm RNA,NF-κB m RNA,细胞色素芳香化酶(P450 arom)m RNA,环加氧酶2(COX-2)m RNA的表达。结果治疗后来曲唑组子宫异位内膜体积较对照组显著降低[(158±23)mm3vs(28±3)mm3],差异有统计学意义(P<0.05)。来曲唑组雌二醇、孕酮水平均显著低于对照组[(30.5±1.6)ng/L vs(38.6±1.9)ng/L,(60±6)μg/L VS(37±3)μg/L],差异有统计学意义(P<0.05);来曲唑组大鼠睾酮、促卵泡生成素和促黄体生成素水平均显著高于对照组[(523±65)ng/L vs(1982±271)ng/L,(5.13±0.18)U/L vs(6.42±0.23)U/L,(4.71±0.28)U/L vs(5.91±0.31)U/L],差异有统计学意义(P<0.05)。来曲唑组大鼠异位子宫内膜组织中的ICAM-1、MMP-9和VEGF的表达水平均显著低于对照组[(23.6±2.3)vs(40.8±2.9),(22.7±1.8)vs(39.6±2.8),(28.4±1.8)vs(45.3±1.9)],差异有统计学意义(P<0.05)。来曲唑组IL-6 m RNA,TNF-αm RNA和NF-κB m RNA表达水平均显著低于对照组[(0.281±0.021)vs(0.805±0.012),(0.434±0.011)vs(0.981±0.013),(0.403±0.014)vs(0.972±0.015)],差异有统计学意义(P<0.05)。来曲唑组大鼠异位病灶中P450arom m RNA和COX-2 m RNA表达量显著低于对照组[(0.257±0.024)VS(0.465±0.022),(0.364±0.024)vs(0.471±0.031)],差异有统计学意义(P<0.05)。结论来曲唑对子宫内膜异位症模型大鼠异位病灶具有明显的抑制作用,其作用机制可能是来曲唑能够降低ICAM-1、MMP-9、VEGF、IL-6 m RNA、TNF-αm RNA和NF-κB m RNA等细胞因子的转录水平以及降低P450arom和COX-2等催化酶水平抑制雌激素合成有关。
Objective To research the function mechanism of letrozole in treatment of rat endometriosis model ectopic lesions. Methods The model of endometriosis was established by the endometrial auto-transplantation, 30 rats with successful model were selected and randomly divided into two groups with 15 cases in each, the letrozole group adopted letrozole with0.26 mg/kg once a day for gavage, the control group adopted the 0.9%Na Cl injection for gavage, and the expression of ICAM-1, MMP-9 and VEGF in the ectopic lesion tissues was tested by the immunohistochemical method, and the expression of 6（IL-6）m RNA,（TNF）αm RNA, NF-κB m RNA,（P450arom）m RNA and 2（COX-2）m RNA were tested by the RT-PCR.Results After treatment, ectopic endometrial volume in the letrozole group obviously decreased compared with that in the control group[（158±23）mm3vs（28±3）mm3], and the difference had statistical significance（P 0.05）, and the estradiol and corporin levels in the Letrozole group were obviously lower than those in the control group [（30.5±1.6）ng/L vs（38.6±1.9）ng/L,（60±6）μg/L vs（37±3）μg/L], and the difference had statistical significance（P0.05）, the testoterone, follicle-stimulating hormone and prolan B levels in the letrozole group were obviously higher than those in the control group [（523 ±65）ng/L vs（1982±271）ng/L,（5.13±0.18）U/L vs（6.42±0.23）U/L,（4.71±0.28）U/L vs（5.91±0.31）U/L], and the difference had statistical significance（P0.05）, and the expression level of ICAM-1,MMP-9 and VEGF in the rat ectopic endometrium tissue in the letrozole group was obviously lower than that in the control group[（23.6±2.3）vs（40.8±2.9）,（22.7±1.8）vs（39.6±2.8）,（28.4±1.8）vs（45.3±1.9）], and the difference had statistical significance（P0.05）, and the expression level of IL-6 m RNA,TNF-αm RNA and NF-κB m RNA in the letrozole group was obviously lower than that in the control group[（0.281±0.021） vs（0.805±0.012）,（0.434±0.011） vs（0.981±0.013）,（0.403±0.014） vs（0.972±0.015）], and the difference had statistical significance（P0.05）, and the P450 arom m RNA and COX-2 m RNA expression level in the rat ectopic focus in the Letrozole group was obviously lower than that in the control group [（0.257±0.024）vs（0.465±0.022）,（0.364±0.024）vs（0.471±0.031）], and the difference had statistical significance（P0.05）. Conclusion Letrozole has an obvious restraint effect on the rat endometriosis model ectopic lesions, and the function mechanism may be related to the Letrozole in reducing the transcriptional level of ICAM-1, MMP-9, VEGF, IL-6 m RNA, TNF-αm RNA and NF-κB m RNA and catalase levels such as P450 arom and COX-2 used to inhabit the estrogen biosynthesis.
出处
《中外医疗》
2017年第2期5-9,共5页
China & Foreign Medical Treatment
基金
新疆医科大学科研创新基金(XJC2013207)
