目的 探讨白虎加人参汤对2型糖尿病动物模型骨骼肌特异性胰岛素样生长因子-1受体功能缺失(loss of skeletal muscle-specific insulin-like growth factor-1 receptor function,MKR)小鼠创面感染的作用及机制。方法 MKR小鼠经链脲佐菌素(streptozotocin,STZ)干预与创面滴加耐甲氧西林金黄色葡萄球菌(methicillin-resistant staphylococcus aureus,MRSA)悬液,构建2型糖尿病创面感染模型,随机分为模型组、二甲双胍(0.11 g/kg)组和白虎加人参汤低、高剂量(14、28 g/kg)组,采用同龄FVB/N小鼠作为对照组,每组5只;给药12 d,每4天测量各组小鼠体质量、创面大小、空腹血糖(fasting blood glucose,FBG);实验结束后,采用ELISA法检测小鼠血清中胰岛素、C肽、糖化血清蛋白(glycated serum protein,GSP)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、IL-1β水平,以及血清与胰腺中超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)、谷胱甘肽过氧化物酶(glutathion peroxidase,GPx)活性;采用苏木素-伊红(hematoxylin-eosin,HE)染色观察小鼠胰腺和皮肤创面形态;采用免疫组化染色观察小鼠皮肤组织核因子E2相关因子2(nuclear factor erythroid-2 related factor 2,Nrf2)抗原表达;采用Western blotting法检测皮肤组织Nrf2和血红素氧合酶-1(heme oxygenase-1,HO-1)蛋白表达。结果 与模型组比较,白虎加人参汤高剂量组小鼠伤口显著愈合(P<0.01);糖代谢水平显著改善(P<0.01);血清炎性因子TNF-α、IL-6和IL-1β水平显著下降(P<0.05、0.01);血清与胰腺中抗氧化因子SOD、CAT和GPx活性显著上升(P<0.05、0.01);胰岛β细胞凋亡减少(P<0.01);皮肤组织中Nrf2和HO-1蛋白表达水平显著升高(P<0.01)。结论 白虎加人参汤可能通过改善糖代谢、缓解炎症反应、提高抗氧化能力,保护胰岛β细胞的数量与功能,激活Nrf2/HO-1通路,从而发挥治疗2型糖尿病创面感染的作用。

Objective To investigate the effect and mechanism of Ginseng-plus-Baihu-Tang (白虎加人参汤, GBHT) on wound infection in type 2 diabetes mellitus (T2DM) with loss of skeletal muscle-specific insulin-like growth factor-1 receptor function (MKR). Methods MKR mice were intervened with streptozotocin (STZ) and instilled with methicillin-resistant staphylococcus aureus (MRSA) suspension on wound to establish a wound infection model of T2DM, and then randomly divided into model group, metformin (0.11 g/kg) group, GBHT low- and high-dose (14, 28 g/kg) groups, FVB/N mice of same age were used as control group with five mice in each group; Mice were administered for 12 consecutive days, body weight, wound size and fasting blood glucose (FBG) of mice in each group were measured every four days; After experiment, ELISA was used to detect insulin, C-peptide, glycated serum protein (GSP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β levels in serum of mice, and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in serum and pancreas of mice; Hematoxylin-eosin (HE) staining was used to observe the morphology of mice pancreas and skin wound; Immunohistochemical staining was used to observe the expression of nuclear factor E2-related factor 2 (Nrf2) antigen in mice skin tissue; Western blotting was used to detect Nrf2 and heme oxygenase-1 (HO-1) protein expressions skin tissue. Results Compared with model group, wounds of mice in GBHT high-dose group were significantly healed (P < 0.01); Glucose metabolism level was significantly improved (P < 0.01); Levels of inflammatory factors TNF-α, IL-6 and IL-1β in serum were significantly decreased (P < 0.01, 0.05); Activities of antioxidant factors SOD, CAT and GPx in serum and pancreas were significantly increased (P < 0.05, 0.01); Islet β-cell apoptosis was decreased (P < 0.01); Expressions of Nrf2 and HO-1 protein in skin were significantly increased (P < 0.01). Conclusion GBHT may play a role in the treatment of type 2 diabetes wound infection by improving glucose metabolism, alleviating inflammatory response, increasing antioxidant capacity, protecting the number and function of pancreatic β cells and activating Nrf2/HO-1 pathway.

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国家自然科学基金资助项目（82074400）；国家自然科学基金资助项目（82004185）；湖南省科技厅重点研发计划项目（2020SK2101）；湖南省教育厅科学研究项目（20K094，20B450）；湖南省研究生科研创新项目（CX20200786）