枸橼酸西地那非阴道泡腾片的家兔阴道黏膜刺激性及对子宫内膜厚度的影响

Vaginal Mucosal Irritation and Endometrial Thickness Influence of Sildenafil Citrate Vaginal Effervescent Tablets

目的:考察枸橼酸西地那非(SC)阴道泡腾片的阴道黏膜刺激性,研究其对子宫内膜厚度的影响。方法:以12只健康雌性家兔为实验动物,随机分为3组:生理盐水组、空白泡腾片组及SC泡腾片组,每组4只。生理盐水组给予2 ml生理盐水,另外两组分别给予空白泡腾片或SC泡腾片,1片/只,1次/d,连续给药20 d。给药前和给药后24 h收集家兔阴道灌洗液,检测其中白细胞介素6(IL-6)和肿瘤坏死因子ɑ(TNF-ɑ)的含量。麻醉后处死家兔,取阴道黏膜进行HE染色,显微镜下观察病理变化,并进行刺激分级评分。运用免疫组化技术检测阴道黏膜内核增殖抗原(PCNA)的表达。取子宫样本,石蜡包埋切片,HE染色后测定内膜厚度。抽取腹腔浅部下腔静脉血,用酶化学发光法测定其中促黄体酮生成素(LH)、卵泡刺激素(FSH)、雌二醇(E2)水平。结果:3组阴道灌洗液中给药前及给药后24 h时的IL-6、TNF-ɑ含量均无明显改变(P>0.05);3组兔阴道均无明显病理性改变,黏膜完整,上皮结构清晰,细胞形态正常,均可见少量白细胞浸润,血管充血、水肿轻微,且空白泡腾片组及SC泡腾片组与生理盐水组反应程度相似;刺激指标评分均未超过1分,总分均未超过2分,且各组差异无统计学意义(P>0.05)。与生理盐水组相比,空白泡腾片组及SC泡腾片组阴道黏膜PCNA表达差异无统计学意义(P>0.05)。生理盐水组、空白泡腾片组及SC泡腾片组白兔子宫内膜厚度分别为(0.42±0.16),(0.45±0.22),(0.88±0.11)μm,空白泡腾片组与生理盐水组差异无统计学意义(P>0.05),而SC泡腾片可显著增加白兔子宫内膜厚度(P<0.05)。各组雌激素水平差异无统计学意义(P>0.05)。结论:SC阴道泡腾片局部应用对阴道黏膜刺激性小,并可显著增加子宫内膜厚度。

Objective:To explore the vaginal mucosal irritation of sildenafil citrate(SC)vaginal effervescent tablets,and study the effect of the tablets on endometrial thickness.Methods:Totally 12 female rabbits were randomly divided into 3 groups:saline group,blank effervescent tablets group and SC effervescent tablets group with 4 ones in each group.The saline group was given saline 2 ml,and the other group was given blank effervescent tablet and SC effervescent tablet,respectively,one tablet for each rabbit,once a day for 20 days continuously.Cervicovaginal lavages of rabbits were collected before administration and at 24 h after administration to determine the contents of interleukin-6(IL-6)and tumor necrosis factorα(TNF-α).The rabbits were sacrificed by anesthesia,and the vaginal mucosa was withdrawn,the pathological changes were observed under a microscope after HE staining and the irritation grade score was assessed.The expression of proliferating cell nuclear antigen(PCNA)in vaginal mucosa was detected by immuno-histochemistry assay.The womb was also withdrawn to make slides after paraffin embedding,and the thickness of endometrium was measured after HE staining.Blood samples were withdrawn from superficial inferior vena cana of abdominal cavity,and the levels of luteinizing hormone(LH),follicle stimulating hormone(FSH)and estradiol(E2)were detected by enzyme chemiluminescence.Results:The contents of IL-6 and TNF-ɑshowed no significant changes in the three groups(P>0.05).The vaginal mucosa of rabbits from the three groups all showed no significant pathological changes with complete mucosa,clear epithelium structure,normal cell morphology,a small amount of white blood cell infiltration and slight vascular congestion and dropsy,and the changes in A blank effervescent tablets group and SC effervescent tablets group were similar to those in saline group.The scores of irritation indices for the three groups were all below 1,the total scores were all below 2,and there were no notable differences in the scores among the three groups(P>0.05).Compared to that of saline group,the expression of PCNA in the blank effervescent tablets group and SC effervescent tablets group showed no significant changes(P>0.05).The thickness of endometrium in saline group,blank effervescent tablets group and SC effervescent tablets group was(0.42±0.16),(0.45±0.22)and(0.88±0.11)μm,respectively,and there was no significant difference between blank effervescent tablets group and saline group(P>0.05),while SC effervescent tablets could significantly increase the thickness of endometrium(P<0.05).Conclusion:SC vaginal effervescent tablets show slight vaginal mucosal irritation,and can increase the thickness of endometrium significantly.