| The estrogen-treated murine model of vulvovaginal candidiasis was set up in the experiment is to investigate the pathogenesy of vulvovaginal candidiasis induced by estrogen, to observe the effect of indomethacin on a murine model of vulvovaginal candidiasis and analyze the regulation of indomethacin on the vaginal local immunoreaction in the estrogen-treated murine model of vulvovaginal candidiasis, and to provide the theory for the clinic application of indomethacin. The experiment is devided by two parts: 1)The estrogen-treated murine model of vulvovaginal candidiasis was set up. The vaginal lavage fluid was applied to observe the effect of indomethacin on the hypha formation, Enzyme-linked immunosorbent assay was applied to determine the effect of estrogen and indomethacin on the prostaglandin E2 levels in the vaginal tissues. 2)The estrogen-treated murine model of vulvovaginal candidiasis was also set up. The vaginal lavage fluid and the HE dyeing,PAS dyeing in the vaginal tissues were applied to observe the effect of indomethacin on the murine model of vulvovaginal candidiasis, Immunohistochemistry and Enzyme-linked immunosorbent assay were seperately applied to determine the effect of estrogen and indomethacin on the transforming growth factor-β1 and the interleukin-2 levels in the vaginal tissues.Part I The Significanc of inducing PGE2 Synthesis by estrogen and inhibiting PGE2 Synthesis by Indomethacin in the Murine Model of Estrogen-dependent Vulvovaginal CandidiasisObjective To investigate the pathogenesy of vulvovaginal candidiasis induced by estrogen, and to observe the effect of indomethacin on the murine model of vulvovaginal candidiasis and analyze the mechanism of action.Methods The estrogen-treated murine model of vulvovaginal candidiasis(EI) was set up. We also set up infected but non-estrogen-treated mice(I), estrogen-treated but uninfected mice(E), indomethacin-treated mice(Indo) and naive mice(C). The vaginal lavage fluid and the vaginal tissues were obtained at day 4,7,14 after inoculation and the hypha in the vaginal lavage fluid were observed. Enzyme-linked immunosorbent assay was applied to determine the prostaglandin E2 levels in the vaginal tissues.Results No hypha but spore were observed in the vaginal tissues in Indo. The levels of prostaglandin E2 in the vaginal tissues in E were higher than those in C at day 7 after inoculation(P<0.05); More hypha were observed in EI than those in I in the vaginal lavage fluid, The levels of prostaglandin E2 in the vaginal tissues in EI were higher than those in I at day 4,7 after inoculation(P<0.05, P<0.05); The levels of prostaglandin E2 in the vaginal tissues in Indo were lower than those in EI at day 4,7 after inoculation(P<0.05, P<0.01).Conclusion Estrogen may up-regulate the prostaglandin E2 levels in the murine vaginal tissues, which may be associated with the hypha formation and the onset of vulvovaginal candidiasis. Indomethacin can inhibit the hypha formation. Indomethacin can down-regulate the prostaglandin E2 production in the vaginal tissues, which blocks the function of promoting the hypha forming by prostaglandin E2 and down-regulating the vaginal local anti-infection immunoreaction by prostaglandin E2. Indomethacin have the double effect of inhibiting the hypha forming and strengthening the vaginal local anti-infection immunoreaction in the murine model. The administration of indomethacin intravaginally should be helpful to the treatment of vulvovaginal candidiasis.Part II The Double Effect of Indomethacin on Inhibiting the Hypha Forming and Regulation of Vaginal Local Immunoreaction in the Murine Model of Estrogen-dependent Vulvovaginal CandidiasisObjective To investigate the immunopathogenesis of vulvovaginal candidiasis induced by estrogen, and to observe the effect of indomethacin on a murine model of vulvovaginal candidiasis and analyze the mechanism of action.Methods The estrogen-treated murine model of vulvovaginal candidiasis (EI) was set up. We also set up infected but non-estrogen-treated mice(I), estrogen-treated but uninfected mice(E), indomethacin-treated mice(Indo) and naive mice(C). The hypha in the vaginal lavage fluid and the pathology in the vaginal tissues were observed at day 4,7,14 after inoculation. Immunohistochemistry and Enzyme-linked immunosorbent assay were seperately applied to determine the growth factor-β1 levels and the interleukin-2 levels in the vaginal tissues.Results No hypha but spore were seen in the vaginal lavage fluid and the vaginal mucosa in Indo. The levels of growth factor-β1 in the murine vaginal tissues in E were higher than those in C at day 4,7 after inoculation(P<0.05, P<0.05 ), The levels of growth factor-β1 in the murine vaginal tissues in I were higher than those in C at day 4,7 after inoculation(P<0.01, P<0.01). The levels of interleukin-2 in the murine vaginal tissues in E were lower than those in C at day 7 after inoculation (P<0.05); More hypha were observed in the vaginal lavage fluid and the vaginal mucosa in EI than those in I, The levels of growth factor-β1 in the murine vaginal tissues in EI were higher than those in I at day 4,7 after inoculation (P<0.05, P<0.05); The levels of interleukin-2 in the murine vaginal tissues in EI and I had no difference with those in C. The levels of growth factor-β1 in the murine vaginal tissues in Indo were lower than those in EI at day 4,7 after inoculation(P<0.01, P<0.01), The levels of interleukin-2 in the murine vaginal tissues in Indo were higher than those in EI at day 4,7 after inoculation (P<0.05, P<0.01).Conclusion Estrogen may up-regulate the growth factor-β1 levels and down-regulate the interleukin-2 levels in the murine vaginal tissues, which may be associated with down-regulating the local immune function in the murine vaginal tissues by estrogen and the onset of vulvovaginal candidiasis. Candidal albicans may up-regulate the growth factor-β1 levels in the murine vaginal tissues and no vaginal protective immunoreaction to candidal albicans happens in I and EI. Indomethacin may inhibit the hypha forming and has good anti-infection effect in the murine model. Indomethacin may down-regulate the growth factor-β1 levels and up-regulate the interleukin-2 levels in the murine vaginal tissues. Indomethacin has the double effect of inhibiting the hypha forming and regulating the vaginal local anti-infection immunoreaction in the murine model. So indomethacin should be a new targeted drug to the treatment of vulvovaginal candidiasis.
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