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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-Iα[(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)讲(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[(I.0±0.2)讲(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。
Objective To investigate the effect of sitagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, on the degradation of stromal cell-derived factor-1α (SDF-1α) and pancreatic β-cell regeneration. Methods The rats in high fat and low dose STZ diabetes model were divided into diabetic model group and sitagliptin group, and the normal rats were healthy control group (NC). FPG, FIns, DPP-4, SDF-1α, islet β cell proliferation, C-myc mRNA and Cyclin D1 mRNA. Results Compared with NC group, FPG [(5.0 ± 0.4) vs (26.8 ± 3.6) mmol / L, DPP-4 [14.63 ± 2.19 vs 17.51 ± 2.11], SDF-Iα (2.84 ± 1.97 vs 6.23 ± 1.85), FIns (24.9 ± 7.4) vs (9.1 ± 3.2) mU / L, respectively (P <0.05). Compared with diabetic model group, FPG [(26.8 ± 3.6) vs (10.8 ± 5.4) mmol / L] and DPP-4 [(17.51 ± 2.11) vs (9.33 ± 2.21) (P <0.05). The expression of proliferating cell nuclear antigen (PCNA) in NC group was weakly expressed, the expression of PCNA in diabetic model group was weakly positive, the expression of sagliptin The expression of C-myc mRNA in diabetic model group and sitagliptin group [(I ± 0.2) vs (1.5 ± 0.6) vs (3.7 ± 1.1)] and CyclinD1 mRNA [( 1.0 ± 0.3) vs (1.7 ± 0.5) vs (4.0 ± 0.7)] (all P <0.05). Conclusions Sipagliptin, a DPP-4 inhibitor, inhibits the activity of DPP-4 and blocks the degradation of SDF-1α, enhances the expression of C-myc and Cyclin D1 mRNAs, and promotes the proliferation and regeneration of pancreatic β cells.