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红景天苷对SD大鼠光老化动物模型治疗的研究

Study of salidroside in the treatment of skin photoaging in SD rats models

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【作者】 李坤杰林松发郭燕妮黄豪郑月恋许天星纪超高宏志

【Author】 LI Kun-jie;LIN Song-fa;GUO Yan-ni;The Second Affiliated Hospital of Fujian Medical University;

【通讯作者】 纪超;高宏志;

【机构】 福建医科大学附属第二医院福建医科大学附属第一医院

【摘要】 目的 探讨红景天苷(salidroside,SAL)对皮肤光老化SD大鼠模型治疗的效果。方法 将75只SPF级雄性健康SD大鼠随机均分为对照组、模型组、SAL低剂量组、SAL中剂量组、SAL高剂量组,每组各15只。模型组和SAL组大鼠经紫外线照射制成皮肤光老化动物模型,从制模第5周开始,SAL低、中、高剂量组分别给予SAL(12.5、25.0、50.0 mg/kg)灌胃干预,对照组、模型组灌胃等体积生理盐水,连续干预8周。苏木精-伊红(HE)染色观察大鼠皮肤组织病理情况,酶联免疫吸附试验检测皮肤组织炎性因子、氧化应激因子水平,流式细胞仪检测皮肤组织光老化情况,缺口末端标记法(TUNEL)、Western blot(Western印迹)和免疫组化染色检测皮肤组织凋亡情况和凋亡相关蛋白、胶原代谢蛋白表达水平。连续收集65例并发胰岛素抵抗的患者(胰岛素抵抗组),130例单纯痤疮患者,50例健康对照者。对所有受试者进行详细的体格、代谢和性激素检查。结果 对照组大鼠皮肤组织角质层、表皮皮层、真皮层结构清楚且分界清晰,模型组角质层、表皮层、真皮层明显增厚且胶原纤维排列紊乱,ASL低、中、高剂量组角质层、表皮层、真皮层增厚,以及胶原纤维紊乱现象得到明显改善。与对照组相比,模型组大鼠皮肤组织中的活性氧(ROS)、丙二醛(MDA)、一氧化氮(NO)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6水平和环氧化物酶(COX)活性显著升高(P <0.05);超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性显著降低(P<0.05);皮肤组织细胞凋亡指数、半胱氨酸蛋白酶(caspase)-3、caspase-9、Bcl相关X蛋白(Bax)表达和基质金属蛋白酶(MMP)-1、MMP-9、MMP-3阳性率显著升高(P <0.05);B细胞淋巴瘤/白血病(Bcl)-2、转化生长因子(TGF)-β蛋白表达显著降低(P <0.05);与模型组相比,SAL低、中、高剂量组大鼠皮肤组织中的ROS、MDA、NO、TNF-α、IL-6水平和COX活性显著降低(P <0.05),SOD和CAT活性显著升高(P <0.05),细胞凋亡指数、caspase-3、caspase-9、Bax蛋白表达和MMP-1、MMP-9、MMP-3阳性率显著降低(P <0.05),Bcl-2、TGF-β蛋白表达显著升高(P <0.05)。结论 SAL对光老化SD大鼠皮肤具有较好的治疗效果,可能与降低大鼠皮肤组织炎症反应和氧化应激,抑制细胞凋亡、胶原蛋白降解有关。

【Abstract】 Objective To explore the curative effect of salidroside(SAL) on skin photoaging in SD rat models. Methods A total of 75 SPF-level male healthy SD rats were randomly divided into control, model, low-dose, medium-dose, and high-dose SAL groups, with 15 cases in each group. The rats in the model group and the SAL group were made into animal models of skin photoaging by ultraviolet irradiation. From the fifth week after modeling, low-dose, medium-dose and high-dose SAL groups were administered intragastrically with SAL(12.5, 25.0, 50.0 mg/kg), while the control group and model group were administered intragastrically with the same volume of normal saline. All were continuously intervened for 8 weeks. The pathological conditions of skin tissues were observed by HE staining. The levels of inflammatory factors and oxidative stress factors in skin tissues were detected by enzyme-linked immunosorbent assay. The photoaging of skin tissues was detected by flow cytometry. The apoptosis of skin tissues and expression levels of apoptosis-related proteins and collagen metabolism proteins were detected by Td T-mediated d UTP nick end labeling(TUNEL), Western blot and immunohistochemistry. Results In the control group, the structure, and borders of the stratum corneum, epidermis, and dermis of skin tissues were clear. In model group,stratum corneum, epidermis and dermis were significantly thickened, and the arrangement of collagen fibers was disordered. In the lowdose, medium-dose, and high-dose SAL groups, the above situations in the model group were significantly improved. Compared with the control group, levels of reactive oxygen species(ROS), malondialdehyde(MDA), nitric oxide(NO), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and cyclooxygenase(COX) activity were significantly increased in model group(P<0.05), activities of superoxide dismutase(SOD) and catalase(CAT) were significantly decreased(P<0.05), cell apoptosis index, expressions of cysteine proteinase3(caspase-3), cysteine proteinase9(caspase-9) and Bcl-2 associated X protein(Bax), and positive rates of matrix metalloproteinases-1(MMP-1), matrix metalloproteinases-9(MMP-9) and matrix metalloproteinases-3(MMP-3) were significantly increased(P<0.05), and expressions of B cell lymphoma/leukemia-2(Bcl-2) and transforming growth factor-β(TGF-β) were significantly decreased(P<0.05). Compared with the model group, levels of ROS, MDA, NO, TNF-α and IL-6, and COX activity were significantly decreased in low-dose, medium-dose and high-dose SAL groups(P<0.05), activities of SOD and CAT were significantly increased(P<0.05), cell apoptosis index, expression of caspase-3, caspase-9 and Bax, and positive rates of MMP-1, MMP-9 and MMP-3 were significantly decreased(P<0.05), and expression of Bcl-2 and TGF-β was significantly increased(P<0.05). Conclusion The curative effect of SAL is good on skin photoaging in SD rats. It may be related to reducing the inflammatory response and oxidative stress in skin tissues, inhibiting apoptosis and degradation of collagens.

【基金】 福建自然科学基金资助项目(2018J01285)
  • 【文献出处】 实用皮肤病学杂志 ,Journal of Practical Dermatology , 编辑部邮箱 ,2022年02期
  • 【分类号】R285.5
  • 【下载频次】24
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