关键词: 寻常痤疮, 石榴皮, TOR丝氨酸-苏氨酸激酶, 缺氧诱导因子1, α亚基, 维A酸相关孤儿受体γt

Abstract: 【Abstract】 Objective To explore the anti-inflammatory effect of pomegranate peel polyphenols on a rat auriclular model of acne and its mechanism of action. Methods Totally, 36 specific-pathogen-free SD rats were randomly divided into 6 groups: blank group, model group, low-, medium- and high-dose pomegranate peel polyphenol groups and positive control group. In all groups except the blank group, 0.5 ml of 100% oleic acid was applied to the openings of bilateral auricular ducts once a day for 3 consecutive weeks, followed by subcutaneous injections of 50 μl of Propionibacterium acnes suspension at the oleic acid-applied sites once a day for 3 consecutive days, and then the rat auriclular model of acne was established. After the model was confirmed to be successfully established by naked eyes, the low-, medium-, high-dose pomegranate peel polyphenol groups were topically treated with 0.5 mg of 1.4%, 2.8%, 5.6% （mass fraction） pomegranate peel polyphenol ointment respectively, the positive control group was topically treated with 0.5 mg of clindamycin hydrochloride gel, and the blank group and model group were topically treated with the same amount of distilled water. All the topical treatments were performed twice a day for 2 consecutive weeks. Twenty-four hours after the last topical treatment, abdominal aortic blood samples were collected, and enzyme-linked immunosorbent assay （ELISA） was conducted to detect the serum level of interleukin 17 （IL-17） in rats; rat auricular tissues were resected, hematoxylin-eosin （HE） staining was performed to observe histopathological changes of the skin tissues in each group, and immunohistochemical study to determine the expression of mammalian target of rapamycin （mTOR）, hypoxia-inducible factor-1α （HIF-1α）, and retinoic acid-related orphan receptor-γt （RORγt） in local tissues. Data meeting the assumptions of homogeneity of variances were analyzed by using one-way analysis of variance, and those that did not meet the assumptions of homogeneity of variances were analyzed by using Kruskal-Wallis H test; multiple comparisons were performed by using least significant difference-t test. Results Compared with the model group, the pomegranate peel polyphenol groups and positive control group showed marked improvement in cysts, desquamation, crusts and epidermal keratinization, and reduced infiltration of inflammatory factors in the dermis at the modeling site. The serum level of IL-17 was significantly lower in the low-, medium- and high-dose pomegranate peel polyphenol groups （61.03 ± 5.99 ng/L, 55.35 ± 2.24 ng/L, 54.35 ± 4.29 ng/L, respectively）, positive control group （48.11 ± 4.07 ng/L） and blank group （42.10 ± 5.62 ng/L） than in the model group （70.24 ± 3.30 ng/L; t = 3.12, 5.34, 5.70, 8.29, 10.54, respectively, all P＜0.05）. Immunohistochemical study revealed that the HIF-1α expression level was significantly lower in the low-, medium- and high-dose pomegranate peel polyphenol groups （0.29 ± 0.05, 0.29 ± 0.03, 0.33 ± 0.02, respectively） and positive control group （0.30 ± 0.01） than in the model group （0.41 ± 0.04; t = 4.89, 5.50, 3.62, 5.21, respectively, all P＜0.05）; the RORγt expression level was significantly lower in the low- and high-dose pomegranate peel polyphenol groups （0.28 ± 0.02, 0.31 ± 0.04, respectively） than in the model group （0.35 ± 0.02, t = 3.68, 2.18, respectively, both P＜0.05）; there was no significant difference in the mTOR expression level among these groups （P = 0.119）. Conclusion Pomegranate peel polyphenols could improve inflammatory reactions in the rat auriclular model of acne, which may be related to the down-regulation of HIF-1α/RORγt signaling pathway.

Key words: Acne vulgaris, Pericarpium granati, TOR serine-threonine kinases, Hypoxia-inducible factor 1, alpha subunit, Retinoic acid-related orphan receptor γt