2型糖尿病病人外周血同源性磷酸酶-张力蛋白诱导的激酶1、Parkin蛋白、视神经蛋白表达与肾损伤程度的关系研究

Study on relationship between expressions of peripheral blood phosphatase and tensin homologue-induced putative kinase 1, Parkin protein and optineurin and degree of renal injury in patients with type 2 diabetes mellitus

目的探究2型糖尿病(T2DM)病人外周血同源性磷酸酶-张力蛋白诱导的激酶1(PINK1)、Parkin蛋白、视神经蛋白(OPTN)表达及与肾损伤程度关系。方法选取2019年5月至2021年5月河南科技大学第一附属医院156例T2DM病人,根据糖尿病肾病(DN)诊断分期标准,分为非DN组92例、早期DN组(EDN组)38例、临床期DN组(CDN组)26例,另以同期60例健康体检者为健康组。比较四组病人外周血PINK1、Parkin蛋白、OPTN表达量(荧光定量PCR法);采用Pearson相关分析法探究PINK1、Parkin蛋白、OPTN表达量与糖脂代谢空腹血糖、糖化血红蛋白(HbA1c)、总胆固醇、三酰甘油、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)及肾功能指标血尿素氮、血肌酐、预估肾小球滤过率(eGFR)、尿微量白蛋白/尿肌酐(UACR)、24 h尿蛋白排泄率(UAER)相关性,采用多因素logistic回归分析探究DN发生影响因素,绘制ROC曲线分析PINK1、Parkin蛋白、OPTN表达量对DN诊断价值。结果CDN组、EDN组、非DN组、健康组外周血PINK1 mRNA表达量分别为0.31±0.17、0.44±0.20、0.69±0.35、0.73±0.34,Parkin蛋白mRNA分别为0.51±0.12、0.62±0.18、0.79±0.28、0.98±0.35,OPTNmRNA分别为0.05±0.01、0.10±0.03、0.14±0.05、0.18±0.07,四组病人外周血PINK1、Parkin蛋白、OPTN表达量差异有统计学意义(P<0.05),均表现为CDN组<EDN组<非DN组<健康组。T2DM病人外周血PINK1、Parkin蛋白表达量均与空腹血糖、HbA1c、血尿素氮、血肌酐、UACR、UAER呈负相关(P<0.05),与eGFR呈正相关(P<0.05);OPTN与血尿素氮、血肌酐、UACR、UAER呈负相关(P<0.05),与eGFR呈正相关(P<0.05)。糖尿病病程、HbA1c、UACR、UAER是DN的独立危险因素(P<0.05),PINK1、Parkin蛋白、OPTN为其保护因素(P<0.05)。外周血PINK1、Parkin蛋白、OPTN表达量诊断DN的ROC曲线下面积分别为0.709、0.754、0.839。结论T2DM病人外周血PINK1、Parkin蛋白、OPTN表达量均下调,且随着病人肾损伤程度增加而降低,检测外周血PINK1、Parkin蛋白、OPTN表达量对DN有一定诊断价值。

Objective To investigate the expressions of phosphatase and tensin homologue-induced putative kinase 1(PINK1),Par⁃kin protein and optineurin(OPTN)in peripheral blood of patients with type 2 diabetes mellitus(T2DM)and their relationship with the degree of renal injury.Methods A total of 156 patients with T2DM in The First Affiliated Hospital of Henan University of Science and Technology between May 2019 and May 2021 were selected,and divided into non-DN group(92 cases),early DN group(EDN group,38 cases)and clinical DN group(CDN group,26 cases)according to the diagnostic staging criteria of diabetic nephropathy(DN).Anoth⁃er 60 healthy people with physical examination during the same period were selected as control group.Expression levels of peripheral blood PINK1,Parkin and OPTN were compared among the four groups(fluorescence quantitative PCR).Pearson correlation analysis was applied to explore the correlation between expression levels of PINK1,Parkin and OPTN and glucolipid metabolism[fasting blood glucose,glycosylated hemoglobin(HbA1c),total cholesterol,triglyceride,low density lipoprotein cholesterol(LDL-C),high density lipo⁃protein cholesterol(HDL-C)]and renal function indicators[blood urea nitrogen,serum creatinine,estimated glomerular filtration rate(eGFR),urinary albumin creatinine ratio(UACR),24 h urinary albumin ejection rate(UAER)].Multivariate logistic regression analysis was adopted to explore the influencing factors of DN occurrence,and ROC curve was drawn to analyze the diagnostic value of expres⁃sion levels of PINK1,Parkin and OPTN on DN.Results The expression levels of peripheral blood PINK1 mRNA in CDN group,EDN group,non-DN group and control group were 0.31±0.17,0.44±0.20,0.69±0.35 and 0.73±0.34,and the expression levels of Parkin mRNA were 0.51±0.12,0.62±0.18,0.79±0.28 and 0.98±0.35,and the expression levels of OPTN mRNA were 0.05±0.01,0.10±0.03,0.14±0.05 and 0.18±0.07,respectively.There were statistical differences among the four groups in terms of expression levels of periph⁃eral blood PINK1,Parkin and OPTN(P<0.05),and the above expression levels were shown as CDN group<EDN group<non-DN group<control group(P<0.05).The expression levels of peripheral blood PINK1 and Parkin of patients with T2DM were negatively cor⁃related with fasting blood glucose,HbA1c,blood urea nitrogen,serum creatinine,UACR and UAER(P<0.05),and were positively cor⁃related with eGFR(P<0.05).OPTN was negatively correlated with blood urea nitrogen,serum creatinine,UACR and UAER(P<0.05),and was positively correlated with eGFR(P<0.05).The course of diabetes mellitus,HbA1c,UACR and UAER were independent risk factors for DN(P<0.05),and PINK1,Parkin and OPTN were protective factors(P<0.05).The areas under the ROC curves of expression levels of peripheral blood PINK1,Parkin and OPTN in the diagnosis of DN were 0.709,0.754 and 0.839,respectively.Conclusions The expression levels of PINK1,Parkin and OPTN in peripheral blood of patients with T2DM are all down-regulated,and decrease with the increase of the degree of renal injury.Detection of expression levels of peripheral blood PINK1,Parkin and OPTN has certain diag⁃nostic value on DN.