利拉鲁肽基于NF-κB/NLRP3通路对超重/肥胖糖尿病前期的干预研究  

Intervention study of liraglutide in overweight/obese prediabetes based on NF-κB/NLRP3 pathway

作　　者：傅莉萍[1] 王保法[1] 金剑虹[1] FU Liping;WANG Baofa;JIN Jianhong(Department of Endocrinology,Hangzhou Hospital of Traditional Chinese Medicine,Hangzhou 310007,Zhejiang,China)

机构地区：[1]杭州市中医院内分泌科,浙江杭州310007

出　　处：《中国现代医生》2023年第19期74-77,83,共5页China Modern Doctor

基　　金：浙江省医药卫生科技计划项目(2020KY226)。

摘　　要：目的探讨利拉鲁肽基于核因子κB(nuclear factor-κB,NF-κB)/核苷酸结合寡聚化结构域样受体蛋白(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)通路对超重/肥胖糖尿病前期患者的作用。方法选取2020年4月至2021年3月杭州市中医院收治的超重/肥胖糖尿病前期患者60例,根据随机数字表法将其分为对照组和观察组,每组各30例。对照组患者进行生活方式干预,观察组患者在此基础上给予利拉鲁肽皮下注射。两组患者均干预12周。比较两组患者干预前后的体质量指数(body mass index,BMI)、血糖相关指标[糖化血红蛋白(glycosylated hemoglobin,HbA1c)、空腹血糖(fasting blood glucose,FBG)、餐后2h血糖(2h postprandial blood glucose,2hPBG)、空腹胰岛素(fasting insulin,FINS)、餐后2h胰岛素(2h postprandial insulin,2hPINS)、稳态模型评估的胰岛素抵抗(homeostasis model assessment of insulin resistance,HOMA-IR)指数]、血脂指标[三酰甘油(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)]、炎症因子[白细胞介素(interleukin,IL)-1β、IL-6、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)]、NF-κB、NLRP3蛋白表达水平。结果观察组患者的BMI、FBG、2hPBG、FINS、2hPINS、HbA1c、HOMA-IR指数、TG、TC、LDL-C、IL-6、IL-1β、TNF-α及NF-κB、NLRP3蛋白表达水平均显著低于同期对照组(P<0.05),HDL-C显著高于同期对照组(P<0.05)。观察组患者的IL-6、IL-1β、TNF-α与HOMA-IR指数均呈正相关(r=0.615,0.327,0.343,P<0.05)。结论利拉鲁肽通过抑制NF-κB/NLRP3通路减轻炎症反应,可降低超重/肥胖糖尿病前期患者的体质量,改善糖脂代谢紊乱。Objective To investigate the effect of liraglutide on overweight/obese prediabetes patients based on nuclear factor-κB(NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway.Methods Sixty overweight/obese prediabetes patients admitted to Hangzhou Hospital of Traditional Chinese Medicine from April 2020 to March 2021 were selected and divided into control group and observation group according to random number table method,with 30 cases in each group.The control group received lifestyle intervention,and the observation group received subcutaneous injection of liraglutide on this basis.Both groups were treated for 12 weeks.Body mass index(BMI),blood glucose related indexes[glycosylated hemoglobin(HbA1c),fasting blood glucose(FBG),2h postprandial blood glucose(2hPBG),fasting insulin(FINS),2h postprandial insulin(2hPINS),homeostasis model assessment of insulin resistance(HOMA-IR)index],blood lipid indexes[triglyceride(TG),total cholesterol,(TC),high density lipoprotein-cholesterol(HDL-C),low density lipoprotein-cholesterol(LDL-C)],inflammatory factors[interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α)],NF-κB,NLRP3 protein expression levels were compared between the two groups before and after intervention.Results BMI,FBG,2hPBG,FINS,2hPINS,HbA1c,HOMA-IR index,TG,TC,LDL-C,IL-6,IL-1β,TNF-α,and expression levels of NF-κB and NLRP3 in observation group were significantly lower than those in control group(P<0.05),HDL-C was significantly higher than that of control group(P<0.05).IL-6,IL-1β,TNF-αwere positively correlated with HOMA-IR index in observation group(r=0.615,0.327,0.343,P<0.05).Conclusion Liraglutide reduces inflammation by inhibiting the NF-κB/NLRP3 pathway,reduces body weight in overweight/obese prediabetes patients,and improves glucose and lipid metabolism disorders.

关 键 词：利拉鲁肽 糖尿病前期 超重 肥胖 NF-κB/NLRP3通路 

分 类 号：R589.1[医药卫生—内分泌]