Comparison between the effects of letrozole modeling and dehydroepiandrosterone modeling on the inflammatory state of mice with polycystic ovary syndrome
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维普
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目的 探讨来曲唑(LET)造模与脱氢表雄酮(DHEA)造模对多囊卵巢综合征(PCOS)小鼠炎症状态的影响.方法 将24只无特定病原级4～6周龄雌性C57BL/6小鼠随机分为DHEA对照组、DHEA干预组、LET对照组和LET干预组,每组6只.于每日上午固定时间,分别给予DHEA对照组小鼠皮下注射0.1 mL芝麻油,DHEA干预组小鼠皮下注射0.1 mL DHEA-芝麻油溶液,LET对照组小鼠灌胃0.2 mL生理盐水,LET干预组小鼠灌胃0.2 mL LET-生理盐水溶液;每次给药后对小鼠进行安抚,连续给药21 d.在造模的第2、4、6、8、10、12、14、16、18、20天测量各组小鼠的体质量.造模第11天到第20天,每天上午进行小鼠阴道液涂片,显微镜下计数涂片上有核上皮细胞、角化细胞、白细胞的数量,判断并记录小鼠所处动情时期.造模第22天进行腹腔注射麻醉,摘取眼球取血0.5 mL,采用酶联免疫吸附试验法检测各组小鼠血清雌二醇(E2)、卵泡刺激素(FSH)、睾酮(T)、肿瘤坏死因子-α(TNF-α)、白细胞介素-17A(IL-17A)、白细胞介素-10(IL-10)水平.取血后颈椎脱臼处死小鼠,取双侧卵巢制备卵巢组织切片,苏木精-伊红染色法观察各组小鼠卵巢组织中成熟卵泡、囊性卵泡数量.结果 造模的第2、4、6、8、10、12、14、16、18、20天,4组小鼠体质量比较差异无统计学意义(P＞0.05).DHEA对照组与LET对照组小鼠均存在规律性动情周期,而DHEA干预组与LET干预组小鼠则失去规律动情周期.给药21 d后,4组小鼠血清E2、FSH、T、TNF-α、IL-17A、IL-10水平比较差异有统计学意义(F=22.370、8.754、893.601、58.966、218.815、23.596,P＜0.01).DHEA 干预组小鼠血清 E2、FSH 水平显著低于DHEA对照组,T水平显著高于DHEA对照组(P＜0.01).LET干预组小鼠E2、FSH水平显著低于LET对照组,T水平显著高于LET对照组(P＜0.01).DHEA干预组与LET干预组小鼠血清E2、FSH水平比较差异无统计学意义(P＞0.05);DHEA干预组小鼠血清T水平显著高于LET干预组(P＜0.01).DHEA干预组小鼠血清TNF-α、1L-17A水平显著高于DHEA对照组,IL-10水平显著低于DHEA对照组(P＜0.01).LET干预组小鼠血清TNF-α、IL-17A水平显著高于LET对照组,IL-10水平显著低于LET对照组(P＜0.01).DHEA干预组小鼠血清TNF-α、IL-17A水平显著高于LET干预组,IL-10水平显著低于LET干预组(P＜0.01).给药21 d后,DHEA对照组和LET对照组小鼠卵巢体积正常,显示正常的原始卵泡、初级卵泡、次级卵泡;DHEA干预组小鼠卵巢体积明显减小,无正常形态的原始卵泡、初级卵泡、次级卵泡,囊性卵泡数明显增多;LET干预组小鼠卵巢体积正常,原始卵泡、初级卵泡、次级卵泡数量明显少于LET对照组,且囊性卵泡数明显增多.4组小鼠卵巢组织中成熟卵泡数、囊性卵泡数比较差异均有统计学意义(F=74.6430、17.937,P＜0.01).DHEA干预组小鼠卵巢组织中成熟卵泡数显著少于DHEA对照组(P＜0.01),LET干预组小鼠卵巢组织中成熟卵泡数显著少于LET对照组(P＜0.01).DHEA干预组与LET干预组小鼠卵巢组织中成熟卵泡数比较差异无统计学意义(P＞0.05).DHEA干预组小鼠卵巢组织中囊性卵泡数显著多于DHEA对照组(P＜0.01),LET干预组小鼠卵巢组织中囊性卵泡数显著多于LET对照组(P＜0.01).DHEA干预组小鼠卵巢组织中囊性卵泡数显著多于LET干预组(P＜0.01).结论 DHEA及LET造模均可获得PCOS模型小鼠,但DHEA造模小鼠卵巢组织学改变更显著,炎症状态更显著,高雄激素血症和卵巢组织学特征改变也更为明显.
Objective To investigate the effects of Letrozole(LET)modeling and dehydroepiandrosterone(DHEA)modeling on the inflammatory state of mice with polycystic ovary syndrome(PCOS).Methods Twenty-four 4-to-6-week-old female C57BL/6 mice without specific pathogen were randomly divided into DHEA control group,DHEA intervention group,LET control group,and LET intervention group,with 6 mice in each group.At a fixed time in the morning of each day,mice in the DHEA control group were injected subcutaneously with 0.1 mL of sesame oil,mice in the DHEA intervention group were injected subcutaneously with 0.1 mL of DHEA-sesame oil solution,mice in the LET control group were administered with 0.2 mL of normal saline by gavage,and mice in the LET intervention group were administered with 0.2 mL of LET-normal saline solution by gavage.The mice were administered for 21 consecutive days and tranquilized after each administration.The body mass of the mice in each group was measured on the 2nd,4th,6th,8th,10th,12th,14th,16th,18th and 20th day of modeling.From the 11th to the 20th day of modeling,a smear of vaginal fluid was taken every morning,and the numbers of nucleated epithelial cells,keratinized cells,and leukocytes were counted under the microscope to determine and record the period of estrus.On the 22nd day of modeling,the mice were anesthetized by intraperitoneal injection,and 0.5 mL of blood was collected from the eyeballs;and the levels of estradiol(E2),follicle-stimulating hormone(FSH),testosterone(T),tumor necrosis factor-α(TNF-α),interleukin(IL)-17 A,and IL-10 in serum of mice in each group were measured by using the enzyme-linked immunosorbent assay.The mice were killed by cervical dislocation after blood sampling,and ovarian tissue sections were prepared from both ovaries.The numbers of mature follicles and cystic follicles in the ovarian tissues of mice in each group were counted after hematoxylin-eosin staining.Results On the 2nd,4th,6th,8th,10th,12th,14th,16th,18th and 20th day of modeling,there was no statistically significant difference in the body mass of mice among the four groups(P＞0.05).Regular estrous cycles were observed in mice in the DHEA control group and LET control group,whereas mice in the DHEA intervention group and LET intervention group showed no regular estrous cycles.After 21 days of administration,there were statistically significant differences in serum E2,FSH,T,TNF-α,IL-17A,and IL-10 levels of mice among the four groups(F=22.370,8.754,893.601,58.966,218.815,23.596;P＜0.01).The serum E2 and FSH levels of mice in the DHEA intervention group were significantly lower than those in the DHEA control group,while the T level was significantly higher than that in the DHEA control group(P＜0.01).The serum E2 and FSH levels of mice in the LET intervention group were significantly lower than those in the LET control group,while the T level was significantly higher than that in the LET control group(P＜0.01).There was no statistically significant difference in serum E2 and FSH levels of mice between the DHEA intervention group and the LET intervention group(P＞0.05);the serum T level of mice in the DHEA intervention group was significantly higher than that in the LET intervention group(P＜0.01).The serum TNF-α and IL-17A levels of mice in the DHEA intervention group were significantly higher than those in the DHEA control group,while the IL-10 level was significantly lower than that in the DHEA control group(P＜0.01).The serum TNF-α and IL-17A levels of mice in the LET intervention group were significantly higher than those in the LET control group,while the IL-10 level was significantly lower than that in the LET control group(P＜0.01).The serum TNF-α and IL-17A levels of mice in the DHEA intervention group were significantly higher than those in the LET intervention group,while the IL-10 level was significantly lower than that in the LET intervention group(P＜0.01).After 21 days of administration,the ovaries of mice in the DHEA control group and LET control group were normal in size and also showed normal primordial follicles,primary follicles,and secondary follicles;the ovaries of mice in the DHEA intervention group had a significantly reduced volume,without primordial follicles,primary follicles,or secondary follicles of normal morphology,but with more cystic follicles;the ovaries of mice in the LET intervention group had a normal volume,but primordial follicles,primary follicles,and secondary follicles were significantly less than those in the LET control group,and cystic follicles significantly increased.The differences in the numbers of mature follicles and cystic follicles in the ovarian tissues of mice among the four groups were statistically significant(F=74.6430,17.937;P＜0.01).The number of mature follicles in the ovarian tissues of mice in the DHEA intervention group was significantly less than that in the DHEA control group(P＜0.01),and the number of mature follicles in the ovarian tissues of mice in the LET intervention group was significantly less than that in the LET control group(P＜0.01).There was no statistically significant difference in the number of mature follicles in the ovarian tissues of mice between the DHEA intervention group and the LET intervention group(P＞0.05).The number of cystic follicles in the ovarian tissues of mice in the DHEA intervention group was significantly more than that in the DHEA control group(P＜0.01),and the number of cystic follicles in the ovarian tissues of mice in the LET intervention group was significantly more than that in the LET control group(P＜0.01).The number of cystic follicles in the ovarian tissues of mice in the DHEA intervention group was significantly more than that in the LET intervention group(P＜0.01).Conclusion Both DHEA and LET modeling can obtain PCOS model mice,but DHEA modeling mice have more significant histological changes,more significant inflammations,and more obvious hyperandrogenemia and morphological changes in the ovarian tissues.
维普
万方数据
