| Vulvovaginal candidiasis (VVC) is an extremely common mucosal fungal infectious disease , Approximately 75% of women will have a vaginal infection episode at least once during their life span.and about 5% have a recurrence, which affects large numbers of women's physical and mental health. The majority of cases of vulvovaginal candidiasis are caused by Candida albicans; about account to 70%-90%。Dimorphism of C. albicans means yeast and hyphal growth forms. Pathogenicity of C. albicans is correlated with of the cell from a yeast form to a filamentous form. The hyphal formation of C. albicans was thought to be more adherent than the yeast form and hyphal was more likely to penetrate tissue. Even worse is that can escape from host immune defenses , moreover, it can escape from host immune defenses. PGE2 plays a crucial role in morphogeny of C. albicans from yeast to hyphal forms,and candida albicans can not only induces selectively transcriptional activation of cyclooxygenase-2 and production of PGE2 in host cells but also produce PGE2 by itself during the infection,while the infected host tissue releases PGE2 too。A vicious cycle seems to be operative in VVC. Yeast and hyphal form play different role in the pathogenicity of C. albicans, resulting in different host immunoreaction following yeast and hyphal stimulation. Yeast form of C. albicans colonizes in vagina as normal flora and host immunoreaction against yeast induces Th1 polarization; hyphae enhance its virulence and also can escape from the host defense with Th1 immunosuppression. C. albicans produces considerable PGE2 and release more active materials which down-regulate vaginal local cell immunity during the infection . To date, the treatment of Vulvovaginal candidiasis is systemic and (or) local administration of antifungal agent, instead not improving the local protective cell mediated immunity, there has been no effect on the re-infection and the protective cell mediated immunity of the host in the situation of C. albicans infection. According to the clinical research extending the period of antifungal treatment of some patients still unable to prevent from the recurrence of symptoms and may not fully recover their immune responsiveness, ecen worse is that which brought the birth of drug resistant strains. In conclusion, to find the immunological factors and seek the drug which have double effect on inhibiting the hypha forming and regulation of vaginal local immunoreaction in Vulvovaginal Candidiasis is the aim in the future.It has been confirmed that indomethacin could significantly inhibit the hypha forming in the international research in vitro and our murine model of estrogen-dependent vulvovaginal candidiasis,while IL-2 level was up-regulated ,the expression of TGF -β1 was down-regulated and PGE2 production showed a significantly decline in the viginal local tissue of the model mice with intravaginal administation of indomethacin. It indicates that indomethacin can promote the local protective cell mediated immunity in the murine model of estrogen-dependent vulvovaginal Candidiasis. At present experiment,setting up the estrogen-treated murine model of vulvovaginal candidiasis is to observe the effect of indomethacin on interlenkin-12,interlenkin-10 and interlenkin-1βlevels expression in the vaginal tissues of the murine model and analyze the regulation of indomethacin on the vaginal local immunoreaction, to provide the theoretical support for the clinic treatment VVC with intravaginal administration of indomethacin .Objective: To observe the effect of indomethacin on cytokines in the murine model of vulvovaginal candidiasis.Methods: The estrogen-treated murine model of vulvovaginal candidiasis(Group EI) was established by injecting subcutaneously with ectogenic estrogen to sustain the state of pseudoestrus of mice and then inoculating intravaginally with 5×104 C. albicans blastoconidia to mice. We also set up infected but non-estrogen-treated mice (Group I), estrogen-treated but uninfected mice(Group E), indomethacin-treated the model mice(Group Indo) and naive mice(Group 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. Then vaginal tissues were carried out HE dying and PAS dying. Enzyme-linked immunosorbent assay was applied to determine the interlenkin-12p70,interlenkin-10 and interlenkin-1βlevels in the vaginal tissues.Results: No hypha but spore were observed in the vaginal tissues in Indo, Vaginal tissues and vaginal lavage fluid of group EI contained large masses of hyphae in superficial mucosa. The levels of IL-1βin the vaginal tissues from the mice in group EI,group I were higher than those in group C at day 4th,7th,14th after inoculation(P<0.05 or P<0.01 );and it was markedly elevated at day 7th after inoculation in group E (P<0.05). The levels of IL-12p70 in the vaginal tissues from the mice in group EI were lower than those in group C at day 7th after inoculation(P<0.05); The levels of IL-10 in the vaginal tissues from the mice in group EI,group E and group I were higher than those in group C at day 7th after inoculation(P<0.01). The levels of IL-10,IL-1βin group Indo were significantly lower and the levels of IL-12p70 were significantly higher than those in group EI (P<0.05).Conclusion: Indomethacin can inhibit the hypha forming and have a reverse effect on the levels of Th1 and Th2 type cytokines in the vaginal local immunoreaction of the murine model. Indomethacin may down-regulate the IL-β1,IL-10 levels and up-regulate the IL-12p70 level in the murine model of estrogen-dependent vulvovagina candidiasis, and enhance vaginal local immunoreaction. Thus indomethacin has the double effects on inhibition the hypha...
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