基于NLRP3炎症小体研究降脂理肝汤治疗T2DM合并NAFLD的疗效及机制

Study on the Efficacy and Mechanism of Jiangzhi Ligan Decoction in the Treatment of T2DM with NAFLD Based on NLRP3 Inflammasome

基于NOD样受体热蛋白结构域相关蛋白3(Nod-like receptor,pyrin domain containing 3,NLRP3)炎症小体研究降脂理肝汤治疗2型糖尿病(Type 2 diabetes mellitus,T2DM)合并非酒精性脂肪肝(Nonalcoholic fatty liver disease,NAFLD)的疗效及机制。选择2018年1月~2020年8月期间本院收治的204例初诊2型糖尿病合并NAFLD患者,随机分为联合治疗组(n=102)和对照组(n=102)。对照组口服盐酸二甲双胍片,500 mg/次,3次/d,联合治疗组在对照组基础上加用降脂理肝汤,1剂/d,两组均连续治疗3个月。比较两组的临床疗效,治疗前后检测空腹血糖(Fasting blood glucose,FBG)、空腹血胰岛素(Fasting blood insulin,F-Ins)、糖化血红蛋白(Hemoglobin A1c,HbA1c)、胰岛素抵抗指数(Homeostasis model assessment of insulin resistance,HOMA-IR)、总胆固醇(Total cholesterol,TC)、甘油三酯(Triglycerides,TG)、低密度脂蛋白胆固醇(Low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(High-density lipoprotein cholesterol,HDL-C)、脂肪肝指数(Fatty liver index,FLI)、白介素-1β(Interleukin-1β,IL-1β)及白介素-18(Interleukin-18,IL-18)含量、外周血NLRP3 mRNA及凋亡相关斑点样蛋白(Apoptosis-asociated speck-like protein containing a CARD,ASC)mRNA表达水平的变化。结果显示联合治疗组的总有效率高于对照组(P<0.05)。治疗后,与各组治疗前相比,2组患者的FBG、F-Ins、HbA1c、HOMA-IR、TC、TG、LDL-C水平均显著降低(P<0.05),HDL-C水平显著升高(P<0.05),联合治疗组患者的FLI水平、IL-1β、IL-18、NLRP3 mRNA及ASC mRNA表达水平均显著降低(P<0.05),对照组患者的FLI水平、IL-1β、IL-18、NLRP3 mRNA及ASC mRNA表达水平与治疗前比较无显著统计学差异(P>0.05)。联合治疗组F-Ins、HOMA-IR、TC、LDL-C、FLI、IL-1β、IL-18、NLRP3 mRNA及ASC mRNA表达水平均显著低于对照组(P<0.05),FBG、HbA1c、TG、HDL-C水平与对照组比较无显著统计学差异(P>0.05)。降脂理肝汤治疗初诊2型糖尿病合并NAFLD能够改善胰岛素敏感性及脂代谢,可能与抑制NLRP3炎症小体的激活有关。

To study the efficacy and mechanism of Jiangzhi Ligan Decoction in the treatment of type 2 diabetes mellitus(T2 DM)with nonalcoholic fatty liver disease(NAFLD)based on Nod-like receptor,pyrin domain containing 3(NLRP3)inflammasome,204 patients with newly diagnosed T2 DM with NAFLD in the authors′hospital from January 2018 to August 2020 were randomly divided into combined treatment group(n=102)and control group(n=102).The control group was treated with metformin hydrochloride tablets,500 mg/time,3 times/d,while the combined treatment group was treated with Jiangzhi Ligan decoction,1 dose/d,on the basis of the control group,for 3 months.The clinical efficacy of 2 groups were compared.The fasting blood glucose(FBG),fasting blood insulin(F-Ins),glycosylated hemoglobin(HbA1 c),insulin resistance index(HOMA-IR),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),interleukin-1β(IL-1β)and interleukin-18(IL-18)contents,the expression of NLRP3 mRNA and ASC mRNA in peripheral blood before and after treatment were detected.The total effective rate of the combined treatment group was higher than that of the control group(P<0.05).After treatment,the levels of FBG,F-Ins,HbA1 c,HOMA-IR,TC,TG,LDL-C of 2 groups significantly decreased,while the level of HDL-C significantly increased(P<0.05),the FLI,IL-1β,IL-18,NLRP3 mRNA and ASC mRNA of the combined treatment group significantly decreased(P<0.05),the FLI,IL-1β,IL-18,NLRP3 mRNA and ASC mRNA of the control group had no significant difference compared with those before treatment(P>0.05).The F-Ins,HOMA-IR,TC,LDL-C,FLI,IL-1β,IL-18,NLRP3 mRNA and ASC mRNA in the combined treatment group were significantly lower than those in the control group(P<0.05),while the levels of FBG,HbA1 c,TG,HDL-C had no significant difference of 2 groups(P>0.05).Jiangzhi Ligan decoction can improve insulin sensitivity and lipid metabolism in the treatment of newly diagnosed T2 DM with NAFLD,which may be related to inhibiting the activation of NLRP3 inflammasome.