红景天苷对糖尿病足溃疡大鼠 Nrf2 / Keap1 信号通路及伤口愈合的影响
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1.青海大学附属医院临床药学科,西宁 810000;2.青海大学附属医院整形门诊,西宁 810000

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R-33

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Effects of salidroside on the Nrf2 / Keap1 signaling pathway and wound healing in rats with diabetic foot ulcer
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1.Department of Clinical Pharmacy, Qinghai University Affiliated Hospital, Xining 810000, China. 2. Plastic Surgery Clinic, Qinghai University Affiliated Hospital, Xining 810000

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    摘要:

    目的 探究红景天苷(Sal)对糖尿病足溃疡(DFU)大鼠核转录因子 E2 相关因子 2 / Kelch 样环氧氯丙烷相关蛋白 1(Nrf2 / Keap1)信号通路及伤口愈合的影响。 方法 采用高脂高糖饲料喂养结合腹腔注射链脲佐菌素(STZ)建立糖尿病大鼠模型,并于足背部除毛剪皮至筋膜,制作面积约为 3 mm×7 mm 的溃疡创面建立 DFU 大鼠模型,随机分为 DFU 模型组(DFU 组)、Sal 低( Sal-L,0. 1 g / ( kg·d))、中( Sal-M,0. 2 g / ( kg·d))高( Sal-H,0. 3 g / (kg·d))剂量组,阳性药物二甲双胍组(MET 组,0. 65 g / (kg·d)),另设血糖正常创面大鼠为对照组(NC 组),连续灌胃 2 周。分别于治疗第 7 天、第 14 天后检测各组大鼠体重及空腹血糖(FBG)水平,免疫组化检测创面组织 CD34 表达情况,计算创面微血管密度(MVD);生物化学法测定创面组织 MDA、SOD 水平;免疫印迹(Western blot) 检测创面组织 Nrf2、Keap1 蛋白表达。 结果 治疗第 0 天各组大鼠体重之间比较无统计学意义(P>0. 05) ,各组 DFU 组、Sal-L 组、Sal-M 组、Sal-H 组、MET 组大鼠 FBG 水平均高于 NC 组(P<0. 05) ;治疗第 7 天、第 14 天,与 NC 组比较,DFU 组、Sal-L 组、Sal-M 组、Sal-H 组、MET 组大鼠体重、FBG 水平、MDA 含量、Keap1 蛋白表达量均升高 (P<0. 05) ,创面愈合率、CD34 阳性细胞、MVD、SOD 活性、Nrf2 蛋白表达量显著降低(P<0. 05) ;与 DFU 组比较, Sal-L 组、Sal-M 组、Sal-H 组、MET 组大鼠体重、FBG 水平、MDA 含量、Keap1 蛋白表达量均显著降低(P<0. 05) ,创面愈合率、CD34 阳性细胞、MVD、SOD 活性、Nrf2 蛋白表达量显著升高(P<0. 05) ,其中 Sal-L 组与 MET 组差异无统计学意义(P>0. 05) 。 结论 Sal 可能通过调节 Nrf2 / Keap1 信号通路,增加 DFU 大鼠抗氧化能力,促进创面愈合。

    Abstract:

    Objective To explore the effects of salidroside ( SAL) on nuclear transcription factor-E2 related factor 2 / Kelch-like epichlorohydrin-related protein 1 ( Nrf2 / Keap1) signaling pathway and wound healing in rats with diabetic foot ulcer (DFU). Methods Diabetes was induced in rats by feeding of a high-fat and high-glucose diet and intraperitoneal injecting of streptozotocin (STZ), and the back of the foot was shaved and cut to the fascia to create an ulcer wound with an area of approximately 3 mm×7 mm to establish DFU rat model. The rats were randomly allocated to a DFU model group; Sal-L (0. 1 g(kg·d)), Sal-M (0. 2 g / (kg·d)), Sal-H (0. 3 g( kg·d)) groups, metformin group (MET, 0. 65 g / (kg·d)), and set normal blood glucose wound rats as the control group (NC group), and all were gavaged daily for 2 weeks. The body mass and concentration of fasting-blood glucose (FBG) of all the rats were measured on the 7th and 14th days of treatment; the expression of CD34 was assessed by immunohistochemistry; the microvascular density (MVD) of the wounds was calculated; the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) concentrations were measured biochemically, and the expression of Nrf2 and Keap1 proteins in the wound tissue was measured by Western blot. Results Prior to the start of treatment, there was no significant difference in the body masse between the groups, while the FBG of the DFU, Sal-L, Sal-M, Sal-H, and MET groups was higher than that of the NC group (P<0. 05). On the 7th and 14th day of treatment, the body mass, FBG, MDA content, and Keap1 protein expression in the DFU, Sal-L, Sal-M, Sal- H, and MET groups were higher than those in the NC group (P<0. 05); and the wound healing rate, CD34 positive cells, MVD, SOD activity, and Nrf2 protein expression were significantly lower (P<0. 05). The body mass, FBG, MDA content, and Keap1 protein expression in the Sal-L, Sal-M, Sal-H, and MET groups were lower than those in the DFU group (P< 0. 05); and the wound healing rate, CD34 positive cells, MVD, SOD activity, and Nrf2 protein expression were significantly higher (P<0. 05). However, there were no significant differences between the Sal-L and MET groups (P> 0. 05). Conclusions Sal may increase the antioxidant capacity and promote wound healing in rats with DFU via the Nrf2 / Keap1 signaling pathway.

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景 亮,祁永章.红景天苷对糖尿病足溃疡大鼠 Nrf2 / Keap1 信号通路及伤口愈合的影响[J].中国比较医学杂志,2021,31(8):48~54.

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  • 收稿日期:2020-09-25
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  • 在线发布日期: 2021-09-26
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