基于TLR4/MyD88/NF-κB信号通路介导慢性炎症探讨西北燥证型糖尿病(外燥内湿证)的相关性研究  

Study on the Correlation of Northwest Dryness Type Diabetes(External Dryness and Internal Dampness Type)Based on TLR4/MyD88/NF-κB Signaling Pathway-mediated Chronic Inflammation

作　　者：马丹 邓德强 肖艳 秋金玲 王迪 邓佳铭 张淼 侯世佳 董秋格 黄诗雄 高旋 罗汇款 何敏[3] 胡冰虹 高晓丁 高以晴 毕瑞雪 支楚莹 MA Dan;DENG Deqiang;XIAO Yan;QIU Jinling;WANG Di;DENG Jiaming;ZHANG Miao;HOU Shijia;DONG Qiuge;HUANG Shixiong;GAO Xuan;LUO Huikuan;HE Min;HU Binghong;GAO Xiaoding;GAO Yiqing;BI Ruixue;ZHI Chuying(State Key Laboratory of Pathogenesis and Prevention of High Altitude Disease in Central Asia,Urumqi 830000,Xinjiang,China;Affiliated Hospital of Xinjiang Second Medical College,Urumqi Hospital of Traditional Chinese Medicine,Urumqi 830002,Xinjiang,China;Xinjiang Medical University,Urumqi 830000,Xinjiang,China)

机构地区：[1]省部共建中亚高发病成因与防治国家重点实验室,新疆乌鲁木齐830000 [2]新疆第二医学院附属医院,乌鲁木齐市中医医院,新疆乌鲁木齐830002 [3]新疆医科大学,新疆乌鲁木齐830000

出　　处：《辽宁中医药大学学报》2024年第8期158-165,共8页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：新疆省部共建中亚高发病成因与防治国家重点实验室开放课题项目(SKL-HIDCA-2021-ZY5)。

摘　　要：目的基于TLR4/MyD88/NF-κB信号通路介导慢性炎症探讨西北燥证型糖尿病(外燥内湿证)的降糖机制研究。方法将SD大鼠随机分为正常对照组(对照组)、2型糖尿病模型组(T2DM组)、西北燥证+T2DM大鼠组(西北燥证组)、单纯内湿型T2DM大鼠组(内湿型组),每组6只。采用ELISA检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-16(IL-16)、糖化血红蛋白(GHbA1c)、胰岛素(INS)含量的表达情况,计算胰岛素抵抗指数(HOMA-IR),开展葡萄糖耐量试验和胰岛素耐量试验,生化检测肝功能和血脂四项,生化检测超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、丙二醛(MDA)、肝/肌糖原表达情况,HE和PAS检测组织病理变化,实时荧光定量PCR检测干扰素调节因子5(IRF-5)、人核因子-κB亚基P65(NF-κB p65)的mRNA表达变化,蛋白质印迹法(Western blot)检测IRF-5、NF-κB p65、髓样分化初级应答基因88(MyD88)的蛋白表达。结果研究发现西北燥证组的血糖、糖化血红蛋白、胰岛素水平、葡萄糖耐量、胰岛素释放、HOMA-IR、TNF-α、IL-1β、IL-16、MDA、血脂、肝功异常水平较T2DM组显著升高(P<0.05);西北燥证组的SOD、GSH-PX、肝糖原、脏/体比较T2DM组显著降低(P<0.05);西北燥证组的IRF-5、NF-κB p65 mRNA表达水平,TLR4、MyD88、NF-κB p65的蛋白表达水平较T2DM组显著升高(P<0.05)。结论通过观察TLR4/MyD88/NF-κB通路介导的肝脏及脂肪组织慢性炎症的变化情况,发现此种炎症的变化可能与促进糖尿病及胰岛素抵抗的发生发展呈正相关性。Objective To explore the hypoglycemic mechanism of northwest dryness type diabetes(exterior dryness and interior dampness type)based on TLR4/MyD88/NF-κB signaling pathway mediated chronic inflammation.Methods SD rats were randomly divided into normal control group(control group),type 2 diabetes model group(T2DM group),northwest dryness syndrome+T2DM rat group(northwest dryness syndrome group),and simple internal dampness type T2DM rats group(internal dampness type group),with 6 rats in each group.ELISA was used to detect the expression levels of TNF-α,IL-1β,IL-16,HbA1c,and INS.HOMA-IR was calculated,and glucose and insulin tolerance tests were conducted.Biochemical tests were performed on liver function and blood lipids.Biochemical tests were performed on SOD,GSH-PX,MDA,and liver/muscle glycogen expression.HE and PAS were used to detect tissue pathological changes.Real time fluorescence quantitative PCR was used to detect mRNA expression changes of IRF-5,NF-κB p65,and protein expression of IRF-5,NF-κB p65,and MyD88 were detected using Western blotting.Results The study found that the blood glucose,glycated hemoglobin,insulin levels,glucose tolerance,insulin release,HOMA-IR evaluation,and TNF-α,IL-1β,IL-16,MDA,the levels of blood lipid and abnormal liver function were significantly higher than those of T2DM group(P<0.05);the SOD,GSH-PX,liver glycogen,and viscera of northwest dryness group were significantly lower than those of T2DM group(P<0.05);the levels of IRF5,NF-κB p65 mRNA expression,and the levels of TLR4,MyD88,NF-κB p65 protein expression were significantly higher than those of T2DM group(P<0.05).Conclusion By observing the changes of chronic inflammation in liver and adipose tissue mediated by TLR4/MyD88/NF-κB pathway,we found that the changes of such inflammation may be positively correlated with the promotion of diabetes and the development of insulin resistance.

关 键 词：西北燥证 氧化应激 胰岛素抵抗 2型糖尿病 

分 类 号：R255.4[医药卫生—中医内科学]