髓源性生长因子对2型糖尿病小鼠胰岛素抵抗及肝脏炎性反应的影响
Effects of myeloid-derived growth factor on insulin resistance and inflammatory response of liver from type 2 diabetic mice
苏芳 1付之光 1方文灿 2王莹 2贺明娟 3张永彬4
作者信息
- 1. 100142 北京,空军特色医学中心航空生理鉴定训练研究室
- 2. 100853 北京,解放军医学院
- 3. 430033,武汉市第四医院内分泌科
- 4. 100045,北京核工业医院耳鼻喉科
- 折叠
摘要
目的 观察髓源性生长因子(MYDGF)对 2 型糖尿病小鼠胰岛素抵抗及肝脏炎性反应的影响.方法 C57 小鼠分为对照组,糖尿病组(DM)和MYDGF干预糖尿病组(MYDGF).干预 12 周后,检测空腹血糖(FBG)、胰岛素水平并推算胰岛素抵抗指数(HOMA-IR),血清肿瘤坏死因子α(TNF-α)与白细胞介素 6(IL-6)水平,肝脏超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(Catalase)的酶量,HE染色观察肝脏形态结构,Western blot检测IKKβ/IkBα信号途径.结果 与DM组相比,MYDGF组的FBG[(6.91±0.71)mmol/L vs.(19.46±1.12)mmol/L]、胰岛素水平[(13.29±1.42)mU/L vs.(21.88±1.58)mU/L]与HOMA-IR[(4.08±0.65)vs.(18.90±1.37)]明显降低(P<0.05),TNF-α[(32.17±3.18)ng/L vs.(66.39±4.51)ng/L]、IL-6[(13.65±0.89)ng/L vs.(21.55±3.27)ng/L]浓度明显降低(P<0.05),肝脏 SOD[(297.54±20.43)U/mg vs.(198.32±19.29)U/mg]、GSH-Px[(0.65±0.05)U/mg vs.(0.19±0.04)U/mg]、Catalase[(220.34±19.82)U/mg vs.(134.69±18.81)U/mg]酶量显著增多(P<0.05),肝细胞脂肪变与炎性细胞浸润明显改善,IKKβ[p-IKKβ:IKKβ,(0.97±0.10)vs.(1.39±0.11)]和IkBα[p-IκBα:IκBα,(0.93±0.07)vs.(1.44±0.06)]的磷酸化水平显著升高(P<0.05).结论 MYDGF能改善胰岛素抵抗,其作用可能是通过激活IKKβ/IkBα信号途径减轻肝脏炎症反应.
Abstract
Objective To investigate the effects of myeloid-derived growth factor(MYDGF)on insulin resistance and inflam-matory response of liver from type 2 diabetic mice.Methods C57 mice were randomly divided into Vehicle group,DM group and MYDGF group.After administration for 12 weeks,fasting blood glucose(FBG),insulin and HOMA-IR were determined.Tumor nec-rosis factor-α(TNF-α)and interleukin-6(IL-6)in serum as well as superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and Catalase in the liver were measured.Morphological changes of liver were assessed by HE staining.Phosphorylation levels of IKKβ and IkBα were detected by Western blot.Results Compared with DM group,the levels of FBG[(6.91±0.71)mmol/L vs.(19.46±1.12)mmol/L],and insulin in MYDGF group[(13.29±1.42)Mu/L vs.(21.88±1.58)Mu/L]and HOMA-IR[(4.08±0.65)vs.(18.90±1.37)]obviously decreased(P<0.05).The concentrations of TNF-α[(32.17±3.18)ng/L vs.(66.39±4.51)ng/L]and IL-6[(13.65±0.89)ng/L vs.(21.55±3.27)ng/L]also significantly decreased(P<0.05).Liver SOD[(297.54±20.43)U/mg vs.(198.32±19.29)U/mg],GSH-Px[(0.65±0.05)U/mg vs.(0.19±0.04)U/mg]and Catalase[(220.34±19.82)U/mg vs.(134.69±18.81)U/mg]levels increased(P<0.05);in addition,inflammatory cell infiltration and hepatocyte steatosis attenuated;lastly,phosphorylation levels of IKKβ[p-IKKβ:IKKβ,(0.97±0.10)vs.(1.39±0.11)]and IkBα[p-IκBα:IκBα,(0.93±0.07)vs.(1.44±0.06)]significantly increased(P<0.05)in MYDGF group.Conclusions MYDGF im-proves insulin resistance,which may be attributed to attenuated inflammatory response from diabetic liver via activating the IKKβ/IkBα signaling pathway.
关键词
髓源性生长因子/IKKβ/IkBα信号通路/2/型糖尿病/胰岛素抵抗Key words
myeloid-derived growth factor/IKKβ/IkBα sig-naling pathway/type 2 diabetes/insulin resistance引用本文复制引用
基金项目
武汉市知识创新专项项目(2022020801010556)
出版年
2024