维生素D对糖尿病足溃疡患者组织中维生素D受体、过氧化物酶体增殖物激活受体γ、血管内皮生长因子表达的影响

Effects of Vitamin D on the expression of Vitamin D receptor,peroxidosome proliferator-activated receptorγand vascular endothelial growth factorc in diabetic foot ulcer tissues

目的观察维生素D(VitD)对糖尿病足溃疡(DFU)组织中维生素D受体(VDR)、PPARγ、血管内皮生长因子C(VEGFC)mRNA、蛋白表达的影响,探讨VitD对DFU的保护作用及机制。方法选取2018年8月至2020年1月于遵义医科大学附属医院内分泌科门诊及住院的DFU患者90例,根据VitD水平分为VitD正常组(DFU,n=30)、VitD不足组(VitD不足,n=30)、VitD缺乏组(VitD缺乏,n=30)。VitD不足、VitD缺乏组给予VitD2注射液15 mg肌肉注射,每月1次,共3次12周。同期选取烧伤整形科、骨科手术中切除的多余足部皮肤组织的患者为正常对照组(NC,n=30)。化学发光法检测25羟维生素D[25(OH)D],RT-PCR、Western blot法检测足部溃疡组织中VDR、PPARγ、VEGFC的mRNA、蛋白表达。结果治疗4周后,DFU、VitD不足、VitD缺乏组均未出现痊愈者,溃疡面临床疗效差异有统计学意义(P<0.05)。治疗12周后,各组大部分患者痊愈,溃疡面临床疗效差异无统计学意义(P>0.05)。VitD不足、VitD缺乏组25(OH)D低于NC、DFU组(P<0.05)。VitD缺乏组25(OH)D低于VitD不足组(P<0.05)。与NC组比较,DFU、VitD不足和VitD缺乏组VDR、PPARγ、VEGFC mRNA和蛋白表达水平依次降低(P<0.05)。Pearson相关分析显示,血清25(OH)D与QUICKI水平呈正相关(r=0.247,P<0.05),与TG、LDL-C、FIns、HbA1c、HOMA-IR水平呈负相关(r=-0.197、-0.168、-0.274、-0.215、-0.357,P<0.05)。Logistic回归分析显示,HbA1c、HOMA-IR、TG、LDL-C、25(OH)D、QUICKI是发生DFU的影响因素。结论血清25(OH)D水平可能通过影响溃疡组织中VDR、PPARγ、VEGFC表达影响DFU发生发展。

Objective To explore the effect of Vitamin D on Vitamin D receptor(VDR)、peroxisome proliferator activated receptorγ(PPARγ)andvascular endothelial growth factor C(VEGFC)in type 2 diabetic foot ulcer(DFU),and to evaluate the protective effect of VitD on DFU and its mechanisms.MethodsA total of 90 patients with DFU who were hospitalized in the Department of Endocrinology,Zunyi Medical University Affiliated Hospital Zunyi from August 2018 to January 2020 were enrolled in this study and divided into three groups:patients with normal VitD(DFU group,n=30),patients with insufficient VitD(VitD deficiency group,n=30)and patients lacking VitD(VitD lack group,n=30).VitD deficiency group and VitD lack group were given VitD2 injection 15 mg intramuscularly once a month for 3 times during 12 weeks.At the same time,patients with redundant foot skin tissue in burn plastic surgery and orthopedic surgery were selected as control group(NC group,n=30).25(OH)D was detected by chemiluminescence method.The expression of VDR,PPARγ,VEGFC gene and protein were detected by RTPCR and Western blot.Results After 4 weeks of treatment,the patients did not fully recover in DFU group,VitD deficiency group and VitD lack group,but there was significant difference in clinical efficacy of ulcer surface(P<0.05).After 12 weeks of treatment,most patients recovered in each group,and there was no significant difference in clinical efficacy of ulcer surface(P>0.05).The 25(OH)D level was lower in VitD deficiency and VitD lack group than in NC and DFU group(P<0.05).The 25(OH)D level was lower in VitD deficiency group than in VitD lack group(P<0.05).Compared with NC group,the m RNA expression and protein levels of VDR,PPARγand VEGFC decreased in turn in DFU,VitD deficiency and VitD lack groups(P<0.05).Pearson correlation analysis showed that serum 25(OH)D was positively correlated with QUICKI(r=0.247,P<0.05),and negatively correlated with TG,LDL C,FIns,HbA1 c and HOMAIR(r=-0.197,-0.168,-0.274,-0.215,-0.357,P<0.05).The Logistic regression analysis showed that HbA1 c,HOMAIR,TG,LDLC,25(OH)D and QUICKI were influencing factors for DFU.Conclusion Serum 25(OH)D level might affect the occurrence and development of DFU by affecting the expression of VDR,PPARγand VEGFC in ulcer tissue.