二肽基肽酶4抑制剂西格列汀对胰岛基质细胞衍生因子1α降解及胰岛β细胞再生的影响

摘要

Objective To investigate the influence of DPP-4 inhibitor Sitagliptin on SDF-1α degradation and pancreatic β cell regeneration.Methods Type 2 diabetic rats were prepared and divided into two groups:the model group (n=15) and the Sitagliptin group (n=15).The health rats were collected as control group (NC group,n=15).Fasting blood glucose,fasting insulin,pancreatic DPP-4,SDF-1α,islet β cell proliferation,c-myc mRNA,and cyclinD1 mRNA expression were tested after treatment for 12 weeks and compared among groups.Results After treatment,the fasting blood glucose [(5.0±0.4) vs (26.8 ± 3.6)mmol/L),DPP-4[(14.63±2.19)vs(17.51±2.11)],and SDF-1α[(2.84±1.97)vs(6.23±1.85)] increased,fasting insulin [(24.9±7.4)vs(9.1±3.2)mU/L] decreased in the model group than in the NC group (P<0.05).The fasting blood glucose [(26.8±3.6) vs (10.8±5.4) mmol/L] and DPP-4[(17.51±2.11)vs(9.33±2.21)] decreased (P<0.05),fasting insulin [(9.1±3.2) vs (16.7±6.5) mU/L] and SDF-1α[(6.23±1.85)vs(11.38±2.02)] increased in the Sitagliptin group than in the model group (P<0.05).PCNA expression was weak in the NC group,moderate in the model group and the highest in the Sitagliptin group.The expression of c-myc mRNA and cyclinD1 mRNA increased in the model group and Sitagliptin group than in NC group [c-myc mRNA(1.0±0.2) vs (1.5±0.6)vs(3.7±1.1),P<0.01;CyclinD1 mRNA (1.0±0.3)vs(1.7±0.5)vs (4.0±0.7),P<0.01].Conclusion DPP-4 inhibitor Sitagliptin can inhibit the DPP-4 enzyme activity,block SDF-1α degradation,increase the c-myc mRNA and CyclinD1 mRNA expression in WNT pathway and increase pancreatic β cells proliferation regeneration.%目的 探讨二肽基肽酶4(DPP-4)抑制剂西格列汀对基质细胞衍生因子1α(SDF-1α)降解及胰岛β细胞再生的影响.方法 将高脂-小剂量STZ糖尿病模型大鼠分为糖尿病模型组与西格列汀组,正常大鼠为健康对照(NC)组,给药12 周后测量FPG、FIns、胰腺DPP-4、SDF-1α、胰岛β细胞增殖、细胞骨髓瘤(C-myc) mRNA和细胞周期蛋白 D1(CyclinD1) mRNA.结果 治疗后与NC组比较,糖尿病模型组FPG[(5.0±0.4)vs(26.8±3.6) mmol/L]、DPP-4[(14.63±2.19)vs(17.51±2.11)]、SDF-1α[(2.84±1.97)vs(6.23±1.85)]升高,FIns[(24.9±7.4)vs(9.1±3.2) mU/L]降低(P<0.05);与糖尿病模型组比较,西格列汀组FPG[(26.8±3.6) vs (10.8±5.4) mmol/L]、DPP-4[(17.51±2.11)vs(9.33±2.21)]降低,FIns[(9.1±3.2) vs (16.7±6.5) mU/L]、SDF-1α[(6.23±1.85)vs(11.38±2.02)]增高(P<0.05);NC组增殖细胞核抗原(PCNA)弱表达,糖尿病模型组PCNA弱阳性表达,西格列汀组PCNA强阳性表达;与NC组比较,糖尿病模型组和西格列汀组C-myc mRNA[(1.0±0.2) vs (1.5±0.6)vs(3.7±1.1)] 和CyclinD1 mRNA[(1.0±0.3)vs(1.7±0.5)vs (4.0±0.7)]均升高(P<0.05).结论 DPP-4抑制剂西格列汀可抑制DPP-4酶活性而阻滞SDF-1α降解,提高WNT信号通路靶基因C-myc与Cyclin D1 mRNA表达,促使胰岛β细胞增殖再生.