西格列汀对2型糖尿病合并非酒精性脂肪肝病患者外周血单个核细胞肿瘤坏死因子-α白细胞介素-6及白细胞介素-10 mRNA表达的影响

Effect of sitagliptin on the expression of TNF-α,IL-6 and IL-10 mRNA in peripheral blood mononuclear cells of patients with type 2 diabetes mellitus complicated with NAFLD

目的观察二肽基肽酶4(DPP-4)抑制剂-西格列汀对初发2型糖尿病伴非酒精性脂肪肝病(NAFLD)患者外周血单个核细胞(PBMC)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6及IL-10 mRNA表达的影响。方法选取2019年1月至2019年8月期间在我院确诊的70例初诊2型糖尿病伴脂肪肝患者为研究对象,在饮食控制及适当运动基础上,采用随机数字表法分为观察组(西格列汀组)36例及对照组(二甲双胍组)34例。观察2组患者治疗前和治疗后3个月的肝功能、总胆固醇(TC)、甘油三酯(TG)、空腹血糖(FBG)、空腹胰岛素(FINS)及糖化血红蛋白(HbA1c),并计算胰岛素抵抗指数(HOMA-IR);酶联免疫吸附法检测血清DPP-4、TNF-α、IL-6及IL-10;采用Ficoll Paque梯度分离法中分离出PBMC、实时荧光定量PCR法检测人血外周单个核细胞肿瘤坏死因子TNF-α、白细胞介素IL-6及IL-10mRNA表达。结果治疗3个月后,2组体质量指数(BMI)、血清FBG及FINS、ALT、AST及TG水平、HOMA-IR指数较治疗前均有下降(P<0.05);且观察组西格列汀干预后血清TG水平、HOMA-IR指数较对照组明显下降(P<0.05),而TC水平差异无统计学意义(P>0.05);同时,与二甲双胍组比较,西格列汀组外周血单个核细胞促炎细胞因子TNF-α及IL-6mRNA表达明显下降(P<0.05),抗炎因子IL-10mRNA表达升高(P<0.05)。结论与二甲双胍相比,单用西格列汀可有效改善T2DM合并NAFLD患者胰岛素抵抗、糖脂代谢异常及外周血单个核细胞M1/M2失衡引起的促炎及抗炎细胞因子表达;推断西格列汀可能通过调节外周血单个核细胞M1/M2炎症失衡而改善胰岛素抵抗及糖脂代谢紊乱。

Objective To observe the effect of dipeptidyl peptidase 4(DPP-4)inhibitor sitagliptin on the expression of TNF-α,IL-6 and IL-10 mRNA in peripheral blood mononuclear cells(PBMC)of newly diagnosed type 2 diabetes mellitus patients with NAFLD.Methods Seventy newly diagnosed type 2 diabetes mellitus patients with fatty liver disease diagnosed in our hospital from January to August 2019 were selected as the research subjects.On the basis of diet control and proper exercise,they were randomly divided into observation group/sitagliptin group(36 cases)and control group/metformin group(34 cases).Liver function,total cholesterol(TC),triglyceride(TG),fasting blood glucose(FBG),fasting insulin(fins)and glycosylated hemoglobin HbA1c were observed before and 3 months after treatment,and insulin resistance index(HOMA-IR)was calculated;serum DPP-4,TNF-αIL-6 and IL-10 were detected by enzyme-linked immunosorbent assay.Human peripheral mononuclear cells(PBMC)were isolated by Ficoll paque gradient method.The expression of TNF-α,IL-6 and IL-10 mRNA in PBMC were detected by real-time PCR.Results After 3 months of treatment,BMI,serum FBG,FINS,GPT,ALT and AST levels and HOMA-IR index of the two groups were all decreased compared with those before treatment(P<0.05);and the serum TG level and HOMA-IR index of the observation group after intervention with sitagliptin were significantly lower than those of the control group(P<0.05),but the TC level had no significant difference(P>0.05);at the same time,compared with metformin group,the expression of peripheral blood mononuclear inflammatory cytokines TNF-αand IL-6 mRNA in sitagliptin group decreased significantly(P<0.05),and the expression of anti-inflammatory factor IL-10 increased(P<0.05).Conclusion Compared with metformin,sitagliptin alone can effectively improve the expression of pro-inflammatory and anti-inflammatory cytokines caused by insulin resistance,abnormal glucose and lipid metabolism and M1/M2 imbalance of peripheral blood mononuclear cells in T2DM patients with NAFLD.It is concluded that sitagliptin may improve insulin resistance and glucose and lipid metabolism disorder by regulating M1/M2 inflammatory imbalance of peripheral blood mononuclear cells.