EFFECT OF α-LIPOIC ACID IN INHIBITING OXIDATIVE STRESS AND PROMOTING DIABETIC WOUND HEALING BY SUPPRESSING EXPRESSION OF miR-29b IN MICE_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

 WUJun ¹ , TANGHuiqin ² , LIUQun ¹ , GANDingyun ¹ , ZHOUMan ¹

1. Department of Endocrinology, the Third Hospital of Wuhan, Wuhan Hubei, 430060, P. R. China;
2. Department of Medical Administration, the Health and Family Planning Commission of Hubei Province;

Corresponding?author：

WUJun, Email: luodanwu@sina.com

Keywords：

α-lipoic acid; miR-29b; Oxidative stress; Diabetic foot; Wound healing; Mouse

DOI：

10.7507/1002-1892.20160207

Video：

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Objective To investigate the effect of α-lipoic acid on the oxidative stress of wound tissues and diabetic wound healing in mice with diabetic feet. Methods Sixty male C57BL/6J mice weighting 200-300 g were randomly divided into model group (control group, n=15), α-lipoic acid-treated model group (n=15), miR-29b mimic group (n=15), and miR-29b mimic negative control group (NC group, n=15). All animals received intraperitoneal injection of streptozocin to establish the diabetic model. Then, a full thickness wound of 5 mm×2 mm in size was created at 4 weeks after modeling. All mice were administrated with high-sugar-fat-diet. At the same day after modeling, α-lipoic acid-treated model group was continuously given intravenous injection of 100 mg/(kg·d) α-lipoic acid for 14 days; miR-29b mimic group and NC group received the tail intravenous injection of lentiviral vector for miR-29b mimic and miR-29b mimic negative control (a total of 2×10⁷ TU), respectively, with the treatment of α-lipoic acid. The wound healing was observed and wound area was measured at 7 and 14 days. The wound tissues were harvested to detect the levels of superoxide dismutase (SOD) and glutathione (GSH) using xanthine oxidase method and 5, 5-dithiobis-2-nitrobenzoic acid staining method at 14 days. At the same day, 7, and 14 days after modeling, the relative miR-29b expression in wound tissues from control and α-lipoic acid-treated model groups was detected by real-time fluorescence quantitative PCR. Results All mice survived to the experiment end. The wound healing was faster in α-lipoic acid-treated group than control group. At 7 and 14 days, the relative wound area and miR-29b expression level were significantly lower, while the contents of SOD and GSH were significantly higher in α-lipoic acid-treated group than control group (P < 0.05). In addition, miR-29b mimic group had significantly increased relative wound area and significantly decreased the contents of SOD and GSH when compared with NC group at 7 and 14 days (P < 0.05). Conclusion α-lipoic acid could inhibit oxidative stress and promote diabetic wound healing by suppressing expression of miR-29b in mice.

Citation： WUJun, TANGHuiqin, LIUQun, GANDingyun, ZHOUMan. EFFECT OF α-LIPOIC ACID IN INHIBITING OXIDATIVE STRESS AND PROMOTING DIABETIC WOUND HEALING BY SUPPRESSING EXPRESSION OF miR-29b IN MICE. Chinese Journal of Reparative and Reconstructive Surgery, 2016, 30(8): 1034-1037. doi: 10.7507/1002-1892.20160207 Copy

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12.	郭沛艷, 于德民, 劉德敏. α-硫辛酸對糖尿病小鼠血糖和氧化應激水平的影響.天津醫藥, 2006, 34(11):792-794.
13.	Ji J, Shi J, Budhu A, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med, 2015, 361(15): 1437-1447.
14.	Cheng CJ, Bahal R, Babar IA, et al. MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature, 2015, 518(7537):107-110.
15.	Ciccacci C, Di Fusco D, Cacciotti L, et al. MicroRNA genetic variations:association with type 2 diabetes. Acta Diabetol, 2013, 50(6):867-872.
16.	張麗琴, 鐘樹妹, 韓澤平. 2型糖尿病患者外周血中hsa-miR-29b的表達及臨床意義.現代檢驗醫學雜志, 2014, 29(1):113-114, 116.
17.	梁國威, 宋燕, 邵冬華, 等.初診2型糖尿病患者血清中miR-29a和miR-375表達變化及其與糖、脂標志物相關性研究.中國實驗診斷學, 2013, 17(3):475-478.
18.	陳瑋, 殷荔, 繆愛梅, 等.促炎性細胞因子對大鼠胰島β細胞miR-29家族及抗凋亡蛋白表達水平的影響.南京醫科大學學報(自然科學版), 2015, 35(6):787-792.

1. Peters EJ, Lipsky BA. Diagnosis and management of infection in the diabetic foot. Med Clin North Am, 2013, 97(5):911-946.
2. 楊揚, 魏崗.糖尿病足治療的關鍵-預防為主, 防治結合.大眾健康(理論版), 2012, (8):332-333.
3. Lipsky BA, Apelqvist J, Bakker K, et al. Diabetic foot disease:moving from roadmap to journey. Lancet Diabetes Endocrinol, 2015, 3(9): 674-675.
4. Garcia-Alcala H, Santos Vichido CI, Islas Macedo S, et al. Treatment with α-lipoic acid over 16 weeks in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week highdose loading. J Diabetes Res, 2015, 2015:189857.
5. 段麗君, 劉英, 江霞. α-硫辛酸注射液治療糖尿病足的療效觀察.臨床合理用藥, 2014, 7(2A):55-56.
6. 張麗梅, 吳朝明.硫辛酸注射液聯合彌可保注射液治療糖尿病足的臨床觀察.浙江臨床醫學, 2015, 17(5):791-792.
7. Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol, 2014, 15(8):509-524.
8. Zhu H, Leung SW. Identification of microRNA biomarkers in type 2 diabetes:a meta-analysis of controlled profiling studies. Diabetologia, 2015, 58(5):900-911.
9. Hiller S, DeKroon R, Hamlett ED, et al. Alpha-lipoic acid supplementation protects enzymes from damage by nitrosative and oxidative stress. Biochim Biophys Acta, 2016, 1860(1 Pt A):36-45.
10. 鄭偉英, 金啟輝. α-硫辛酸對輕度糖尿病足病患者胰島素抵抗的影響.浙江醫學, 2012, 34(7):555-556.
11. 錢巧慧, 馮波, 孫梅. α-硫辛酸對2型糖尿病氧化應激狀態和內皮功能的影響.臨床內科雜志, 2006, 23(9):600-601.
12. 郭沛艷, 于德民, 劉德敏. α-硫辛酸對糖尿病小鼠血糖和氧化應激水平的影響.天津醫藥, 2006, 34(11):792-794.
13. Ji J, Shi J, Budhu A, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med, 2015, 361(15): 1437-1447.
14. Cheng CJ, Bahal R, Babar IA, et al. MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature, 2015, 518(7537):107-110.
15. Ciccacci C, Di Fusco D, Cacciotti L, et al. MicroRNA genetic variations:association with type 2 diabetes. Acta Diabetol, 2013, 50(6):867-872.
16. 張麗琴, 鐘樹妹, 韓澤平. 2型糖尿病患者外周血中hsa-miR-29b的表達及臨床意義.現代檢驗醫學雜志, 2014, 29(1):113-114, 116.
17. 梁國威, 宋燕, 邵冬華, 等.初診2型糖尿病患者血清中miR-29a和miR-375表達變化及其與糖、脂標志物相關性研究.中國實驗診斷學, 2013, 17(3):475-478.
18. 陳瑋, 殷荔, 繆愛梅, 等.促炎性細胞因子對大鼠胰島β細胞miR-29家族及抗凋亡蛋白表達水平的影響.南京醫科大學學報(自然科學版), 2015, 35(6):787-792.

Chinese Journal of Reparative and Reconstructive Surgery

EFFECT OF α-LIPOIC ACID IN INHIBITING OXIDATIVE STRESS AND PROMOTING DIABETIC WOUND HEALING BY SUPPRESSING EXPRESSION OF miR-29b IN MICE

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