青蒿琥酯对豚鼠经皮激素诱导后病理性改变的影响
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上海市长宁区卫计委科研基金(20164Y005);上海市同仁医院院级课题基金(TRYJ201508)


Effects of artesunate on pathological changes induced by glucocorticoid in guinea pigs
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    摘要:

    目的:观察青蒿琥酯对豚鼠经皮激素诱导后病理性改变及炎症因子的影响。方法:30只雄性豚鼠背腹部剃毛区外用0.05%丙酸氯倍他索溶液复制模型,并将其随机等分为5组:模型组给予0.9%氯化钠溶液腹腔注射,治疗组分别给予低、中、高剂量[5、10、20 mg/(kg·d)]青蒿琥酯注射液腹腔注射,糖皮质激素受体阻断组给予米非司酮腹腔注射;另取6只豚鼠作为空白对照组,仅剃毛区外涂75%乙醇溶液。观察各组皮肤组织病理学改变,ELISA法检测各组血清中白细胞介素(interleukin,IL)-1、IL-4含量,采用RT-PCR检测各组皮肤中糖皮质激素受体α(GRα)和肿瘤坏死因子(tumor necrosis factor,TNF)-α表达。结果:模型组血清IL-1、IL-4含量明显高于空白对照组和糖皮质激素受体阻断组(P<0.05),青蒿琥酯腹腔注射中、高剂量组血清中IL-1、IL-4含量均低于模型组(P<0.05),治疗组间比较差异无统计学意义。各组豚鼠皮肤组织GRa mRNA的表达差异无统计学意义。模型组皮肤组织TNF-α mRNA含量高于空白对照组,青蒿琥酯腹腔注射中、高剂量组皮肤组织TNF-α mRNA含量低于模型组(P<0.05),中、高剂量组间比较差异无统计学意义。结论:青蒿琥酯能抑制豚鼠类固醇诱导的皮炎,以中、高剂量最为明显,其作用可能与IL-1、IL-4、TNF-α有关,具体机制有待进一步深入研究。

    Abstract:

    Objective:To observe the effect of artesunate on pathological changes and inflammatory factors induced by glucocorticoid in guinea pig models. Methods:Thirty male guinea pigs were used 0.05% clobetasol propionate solution continuously on the shaved belly areas for 30 days to establish guinea pig models of steroid-induced dermatitis. They were randomly and equally divided into 5 groups:model groups were intraperitoneal injected with 0.9% sodium chloride solution,treatment groups were intraperitoneal injected with 5,10 and 20 mg/kg artesunate solution separately,glucocorticoid receptor blocking groups were intraperitoneal injected with mifepristone,and 6 guinea pigs only external used with 75% ethanol solution on shaving back as blank control groups. Pathological changes in skin tissue of each group were observed. Enzyme-linked immunosorbent assay(ELISA)was perfomed to detect the content of IL-1 and IL-4 in the serum of each group. The expressions of GRα mRNA and TNF-α mRNA in the skin of each group were detected by RT-PCR. Results:The levels of IL-1 and IL-4 in the serum of model groups were significantly higher than those in the blank control groups and the glucocorticoid receptor blocked groups. The levels of IL-1 and IL-4 in the serum of artesunate groups were lower than those in the model group(P < 0.05). There was no significant difference between the treatment groups. There was no significant difference in the expression of GRa mRNA in the skin tissues of guinea pigs. The TNF-α mRNA content in the skin tissue of the model group was higher than that in the blank control group and the glucocorticoid receptor blocked group(P < 0.05). The content of TNF-α mRNA in the skin tissue of the high dose and middle dose group of artesunate was lower than that of the model group(P < 0.05). There was no significant difference in TNF-α mRNA between the middle dose artesunate group and the high dose arteunate group. Conclusion:Artesunate can inhibit steroid dermatitis in guinea pig models,especially the middle and high dose artesunate,which may associate with IL-1,IL-4 and TNF-α,and the mechanism needs to be further studied.

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权 哲,张蓓蓓,殷 芳,王婷婷,杜霁儒,支媛婷,钱 苗,刘 玮,许 瑾,宋宁静.青蒿琥酯对豚鼠经皮激素诱导后病理性改变的影响[J].南京医科大学学报(自然科学版),2019,(2):201-204

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  • 收稿日期:2018-11-03
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  • 在线发布日期: 2019-03-06
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