多囊卵巢综合征造模药物对大鼠内分泌和组织结构影响的初步比较

Comparison of effects of three drugs for modeling polycystic ovary syndrome on endocrine and tissue structure in rats

目的探讨不同多囊卵巢综合征(PCOS)模型构建药物对大鼠内分泌和各组织结构的影响。方法选取3~4周龄SD大鼠40只随机分为正常对照组、脱氢表雄酮(DHEA)组、双氢睾酮(DHT)组和来曲唑(LET)组,每组10只,分别皮下注射油剂、6 mg/100 g DHEA、85μg DHT、1 mg/kg LET,每天1次,连续注射21 d。各组大鼠每周称重1次,造模21 d后收集血清和各组织器官并称重。检测各组大鼠血清中性激素和糖脂水平,阴道涂片观察大鼠动情周期排卵情况,HE染色观察各组大鼠心脏等器官组织结构和形态改变情况。结果ELISA检测发现,DHEA组大鼠血清睾酮(T)、雌二醇(E 2)水平显著高于对照组(P<0.05);DHT组大鼠血清E 2、黄体生成素(LH)水平显著高于对照组(P<0.05);LET组大鼠血清T、LH水平显著高于对照组(P<0.05),而E 2水平显著低于对照组(P<0.05)。各造模组动情周期紊乱、排卵功能障碍,其中DHEA组处于动情间期时间最长。DHEA组总胆固醇(TCHO)水平显著高于对照组(P<0.05),DHEA组、LET组血清胰岛素(INS)水平和稳态胰岛素评价指数(HOMA-IR)显著高于对照组(P<0.05),而DHT组糖脂水平及HOMA-IR与对照组比较均无显著性差异(P>0.05)。HE染色显示,DHEA组大鼠大部分肺泡腔轻度塌陷,间质内可见少许淋巴细胞、嗜酸性粒细胞浸润,脾小结生发中心不明显,局部伴纤维组织增生;DHT组和LET组大鼠心脏组织中的局灶细胞间可见少量淋巴细胞浸润;LET组大鼠大部分肺泡间隔增宽,支气管周围淋巴组织增生。结论本研究探索了3种PCOS造模药物对SD大鼠内分泌指标和各组织器官结构的影响,为今后PCOS相关疾病的研究提供一定参考。

Objective:To investigate the effects of different drugs for modeling polycystic ovary syndrome(PCOS)on endocrine and tissue structure in rats.Methods:Forty SD rats aged 3-4 weeks were selected and divided into four groups according to the type of drug used for modeling:dehydroepiandrosterone(DHEA)group,dihydrotestosterone(DHT)group,and letrozole(LET)group and control group,ten for each group.The rats in each group were injected subcutaneously 6 mg/100 g DHEA,85μg DHT,1 mg/kg LET,respectively,once a day for 21 days.The rats were weighed once a week.Serum and tissues were collected and weighed 21 days after modeling.The serum levels of sex hormone,glucose and lipid were detected by ELISA,the status of ovulation in estrous cycle of rats was observed by vaginal smear,and the morphological changes of heart and other organs were observed by HE staining.Results:The serum levels of testosterone(T)and estradiol(E 2)in the DHEA group were significantly higher than those in the control group(P<0.05).The serum levels of E 2 and LH in the DHT group were significantly higher than those in the control group(P<0.05).The serum levels of T and LH in the LET group were significantly higher than those in the control group(P<0.05),while E 2 levels were significantly lower than those in the control group(P<0.05).The estrus cycle was disordered and ovulation function was obstructive in each model group,and DHEA group had the longest estrus interval.The serum total cholesterol(TCHO)in DHEA group was significantly higher than that in control group(P<0.05).The levels of insulin(INS)and HOMA-IR in DHEA group and LET group were significantly higher than those in control group(P<0.05),but there was no significant change between DHT group and control group(P>0.05).The staining results showed that most of the alveolar cavities in DHEA group were slightly collapsed,and infiltration of a few lymphocytic cells and eosinophils could be seen in the stroma.The germinal center of splenic nodule was not obvious,with local fibrous tissue hyperplasia.In DHT group and LET group,a small amount of lymphocyte infiltration was found in the focal cells of heart tissue.In LET group,most of the alveolar septum was widened and the lymphoid tissue around bronchus was proliferated.Conclusions:The effects of three PCOS modeling drugs on endocrine and tissue structures of female rats are investigated,which can provide some reference for the future research of PCOS related diseases.