绿茶多酚表没食子儿茶素没食子酸酯对高脂高糖饮食诱导肥胖小鼠伤口愈合的影响

作者	单位
宁永玲,沃达,袁志莹,何嘉,马恩,彭军,朱伟东,任丹妮	1.福建中医药大学中西医结合研究院（福州 350122）；2.福建省中西医结合老年性疾病重点实验室（福州 350122）；3.福建中医药大学科技创新与转化中心（福州 350122）；4.同济大学医学院（上海 200092）

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中文摘要:

目的评估绿茶多酚表没食子儿茶素没食子酸酯（EGCG）全身性给药对高脂高糖饮食（HFFD）诱导的肥胖小鼠伤口愈合障碍的干预效果。方法 7~8周龄雄性C57BL/6J小鼠经60 kcal%高脂饲料和20%果糖水持续饲养10周后成为肥胖小鼠，周龄及相关条件具有可比性的正常饮食组小鼠为对照。在小鼠尾部进行全层切除伤口造模后，每天腹腔注射EGCG进行干预，连续给药21天。在第0、3、7、14、21天时测量小鼠体重，并对伤口部位进行拍照记录。干预完成后，采用苏木素-伊红（HE）染色法观察小鼠伤口新生皮肤组织形态学；蛋白免疫印迹法（Western Blot）检测小鼠皮肤组织中DNA双链断裂（DSB）特异性生物标志物磷酸化组蛋白H2AX（γ-H2AX）的表达水平。结果与正常饮食组小鼠比较，HFFD肥胖小鼠体重增重>30%（P<0.01），皮肤组织中γ-H2AX表达上调（P<0.05），14天时，模型组伤口面积为正常饮食组的1.97倍；21天时，模型组伤口面积为正常饮食组的4.49倍，差异均有统计学意义（P<0.05，P<0.01）。正常饮食小鼠伤口部位新生皮肤可以重新形成完整的表皮细胞层，肥胖小鼠则表皮细胞过度增殖，基底层细胞和颗粒层细胞分布不典型，角质层变薄。腹腔注射EGCG可使肥胖小鼠皮肤组织中γ-H2AX表达下调（P<0.05）。与模型组小鼠比较，肥胖小鼠经EGCG 5.0、10.0 mg/kg干预后，21天时，中剂量组伤口面积为模型组的0.32倍；高剂量组伤口面积为模型组的0.13倍，差异均有统计学意义（P<0.05，P<0.01）；伤口新生皮肤表皮细胞层结构与正常饮食小鼠相似。结论 EGCG可降低高脂高糖饮食诱导的肥胖小鼠体内DNA损伤，促进伤口愈合及皮肤组织结构重塑，但机制还有待深入研究。

英文摘要:

Objective To evaluate the effect of systemic epigallocatechin gallate （EGCG） administration on impeded wound healing response in obese mice fed with high-fat high-fructose diet （HFFD）. Methods Obesity model was induced in 7- to 8-week-old male C57BL/6J mice fed with HFFD containing high-fat chow （60 kcal% from fat） supplemented with 20% fructose dissolved in drinking water for 10 weeks. Age-matched mice fed a normal diet were used as the control. Mice full-thickness wound-healing models were performed on the dorsal aspect of mice tails， and subsequently injected with either EGCG or deionized water （i.p. daily） for 21 successive days. Mice body weight and degree of wound-healing were measured and photographed on days 0， 3， 7， 14， and 21. On day 21， hematoxylin & eosin （HE） staining was used to observe the morphology of newly formed skin tissues at the wound site， and Western Blot analysis was used to detect the expression of DNA double-strand breaks （DSB） in the mice skin tissue via the specific biomarker γ-H2AX. Results Compared with mice fed a normal diet， the body weight of HFFD-fed obese mouse increased for more than 30% （P<0.01）. γ-H2AX expression of the skin tissue was significantly up-regulated （P<0.05） in obese mice. The wound area of the model group was 1.97 times that of the control group on day 14 （P<0.05， P<0.01）. The wound area of the model group was 4.49 times that of the control group on day 21 （P<0.05， P<0.01）. By day 21 post-wound， mice fed a normal diet had completely recovered epidermis surrounding the newly formed skin tissues at the wound site， while HFFD-fed obese mice had significantly impaired wound-healing response characterized by excessive proliferation of epidermal cells， no typical basal and granular layers， and thinner stratum corneum. Notably， mice intraperitoneal injected with EGCG significantly reduced the level of γ-H2AX expression in the skin tissues of obese mice （P<0.05）. After intervened by EGCG at 5 and 10 mg/kg respectively， the wound area of the middle-dose group was 0.32 times that of the model group， and the wound area of the high-dose group was 0.13 times that of the model group （P<0.05，P<0.01）. The structure of the epidermal cell layer of the wound neonatal skin was similar to that of the normal diet mice. Conclusions Systemic administration of EGCG reduced DNA damage， promoted wound-healing response and skin tissue remodeling in HFFD-fed obese mice. However， the mechanism remains to be further studied.

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