Lidocaine inhibits structural remodeling of vascular wall in diabetic rats by regulating inflammatory response

doi:10.12092/j.issn.1009-2501.2019.07.007

Abstract

Abstract:

AIM: To study the effect of lidocaine on the inflammatory response and vascular smooth muscle cells proliferation and migration of diabetic rats. METHODS: Serum, vascular tissue and primary cultured vascular smooth muscle cells of diabetic model rats and lidocaine-treated diabetic model rats were taken for study. RESULTS:Lidocaine could effectively inhibit the secretion of TNF-α, IL-8 and PAF inflammatory factors, it could be seen that lidocaine could reduce the inflammatory response induced by diabetic cardiovascular disease. Lidocaine could reduce the absorbance of Brdu kit, Ki-67 level, vimentin expression level and the migration area of smooth muscle cells in the scar experiment, indicating that lidocaine could effectively reduce the proliferation and migration of vascular smooth muscle cells. Lidocaine effectively inhibited STAT3 signaling pathway and reduced proliferation and migration of vascular smooth muscle cells. The results were statistically significant (P<0.05). CONCLUSION: Lidocaine can effectively reduce the inflammatory response in diabetic rat model by inhibiting the activation of AKT-STAT3 signaling pathway, and at the same time reduce the abnormal proliferation and migration of vascular smooth muscle cells, thereby improving the vascular wall structure reconstruction. Lidocaine may be a potential therapeutic agent for diabetic cardiovascular disease induced by inflammatory response.

Key words: diabetes, inflammation, vascular remodeling, lidocaine

CLC Number:

SUN Aili, MA Yuetao, WANG Mingcang. Lidocaine inhibits structural remodeling of vascular wall in diabetic rats by regulating inflammatory response[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(7): 766-772.

References

［1］Fitzgerald KR. Review of article: Prevalence of obesity and trends in the distribution of body mass index among US adults［J］. J Vas Nurs, 2013, 31(3): 131-132.
［2］Wang N, Li T, Han P. The effect of tianmai xiaoke pian on insulin resistance through PI3-K/AKT signal pathway［J］. J Diab Res, 2016, 2016(1): 1-8.
［3］Group IDFDA. Update of mortality attributable to diabetes for the IDF Diabetes Atlas: Estimates for the year 2013［J］. Diab Res Clin Prac, 2015, 109(3): 461-465.
［4］Carnagarin R, Dharmarajan AM, Dass CR. Molecular aspects of glucose homeostasis in skeletal muscle-A focus on the molecular mechanisms of insulin resistance［J］. Mol Cel Endocrinol, 2015, 417(C): 52-62.
［5］Low Wang CC, Hess CN, Hiatt WR, et al. Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus-mechanisms, management, and clinical considerations［J］. Circulation, 2016, 133(24): 2459-2502.
［6］Wu J, Saleh MA, Kirabo A, et al. Immune activation caused by vascular oxidation promotes fibrosis and hypertension［J］. J Clin Invest, 2016, 126(4): 1607.
［7］Liu X, Huh JY, Gong H, et al. Lack of mature lymphocytes results in obese but metabolically healthy mice when fed a high-fat diet［J］. Int J Obes, 2015, 39(10): 1548-1557.
［8］Tilg H, Moschen AR. Microbiota and diabetes: an evolving relationship［J］. Gut, 2014, 63(9): 1513-1521.
［9］彭畅,郭润民,吴铿, 等. 糖尿病心肌病代谢重构的分子机制［J］. 中国医学创新, 2017, 14(35): 144-148.
［10］Fabbrini E, Cella M, Mccartney SA, et al. Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals［J］. Gastroenterol, 2013, 145(2): 366-374.
［11］Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease［J］. Nat Med, 2012, 18(3): 363-374.
［12］Ferrante AW. Macrophages, fat, and the emergence of immunometabolism［J］. J Clin Invest, 2013, 123(12): 4992-4993.
［13］张翠, 张根葆, 王继胜, 等. 芒果苷对糖尿病大鼠心肌的保护作用［J］. 中国临床药理学与治疗学, 2016, 21(8): 859-862.
［14］傅永锦, 夏雪怡, 张小牧, 等. 川芎嗪对糖尿病肾病大鼠下调HMGB1表达及降低RAGEs作用［J］. 中国临床药理学与治疗学, 2017, 22(8): 846-851.
［15］Mathis D. Immunological goings-on in visceral adipose tissue［J］. Cell Metab, 2013, 17(6): 851-859.
［16］Wynn TA. Type 2 cytokines: mechanisms and therapeutic strategies［J］. Nat Rev Immunol, 2015, 15(5): 271.
［17］Hill AA, Reid BW, Hasty AH. A decade of progress in adipose tissue macrophage biology［J］. Immunol Rev, 2014, 262(1): 134-152.
［18］Mantovani A, Biswas SK, Galdiero MR, et al. Macrophage plasticity and polarization in tissue repair and remodelling［J］. J Pathol, 2013, 229(2): 176.
［19］倪英群, 谢峰涛, 方朝晖. 基于Wnt/β-链蛋白表达评价丹蛭降糖胶囊对2型糖尿病患者血管的保护作用［J］. 中国临床药理学与治疗学, 2017, 22(5): 531-537.
［20］Wan L, Lin HJ, Huang CC, et al. Galectin-12 enhances inflammation by promoting M1 polarization of macrophages and reduces insulin sensitivity in adipocytes［J］. Glycobiol, 2016, 26(7): 732.
［21］施六霞, 金岳龙, 王祥雨, 等. 高血压、2型糖尿病并发牙周炎患者超敏C-反应蛋白及炎性细胞因子表达分析［J］. 中国临床药理学与治疗学, 2015, 20(5): 541-545.
［22］刘栩晗, 李国生, 李欣宇, 等. 黄连素调节2型糖尿病地鼠内脏脂肪组织FGF21/SIRT1信号通路基因mRNA表达的效应［J］. 中国临床药理学与治疗学, 2016, 21(5): 495-502.
［23］章雅丹. 新型芹菜素纳米脂质体对糖尿病心肌病大鼠心肌细胞凋亡的影响［J］. 医药导报, 2019, 38(5): 555-559.

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