活性维生素D通过STAT-1-TREM-1途径调控M1/M2巨噬细胞表型激活失衡缓解糖尿病肾病中的肾间质纤维化的机制  

Active vitamin D regulates the imbalance of M1/M2 macrophage phenotype activation through the STAT-1-TREM-1 pathway to alleviate the mechanism of renal interstitial fibrosis in diabetic nephropathy

作　　者：张德鱼 于磊 刘艾芹 ZHANG De-yu;YU Lei;LIU Ai-qin(Department of Nephrology,The People's Hospital of the Inner Mongolia Autonomous Region,Hohhot,Inner Mongolia 010017,China)

机构地区：[1]内蒙古自治区人民医院肾内科,内蒙古呼和浩特010017

出　　处：《临床和实验医学杂志》2022年第15期1580-1584,共5页Journal of Clinical and Experimental Medicine

基　　金：内蒙古自治区青年项目(编号:2016086)。

摘　　要：目的 探究活性维生素D通过信号转导和转录激活因子-1(STAT-1)-髓样细胞触发受体-1(TREM-1)途径调控M1/M2巨噬细胞表型激活失衡缓解糖尿病肾病中的肾间质纤维化的机制。方法 45只健康雄性SD大鼠随机数字表法分为对照组、DN模型组和VD治疗组,每组各15只。对照组为正常饲养大鼠,作为实验对照;DN模型组和VD治疗组均建立大鼠糖尿病模型;VD治疗组于糖尿病模型建立后,每日口服VD,剂量为0.1μg/kg。第18周处死大鼠。采集血样用于测量生化参数,并采集肾脏进行组织学检查和分子检测。通过蛋白印迹法检测STAT-1和p-STAT-1蛋白表达。通过自动生化分析仪对大鼠血糖、血尿素氮和血清肌酐进行分析。通过RT-PCR检测大鼠肾组织中Ⅰ型胶原蛋白和纤连蛋白的mRNA表达。通过免疫组织化学分析大鼠肾小球和肾间质CD68巨噬细胞浸润。通过蛋白印迹法分析大鼠肾组织CD163与CD68的蛋白表达。通过RT-PCR分析各组大鼠肾小球和间质内的巨噬细胞分泌的细胞因子肿瘤坏死因子α(TNF-α)、诱导型一氧化氮合酶(iNOS)、Arg-1和MR的浓度。结果 DN模型组STAT-1和p-STAT-1蛋白表达较对照组升高,差异均有统计学意义(P <0.05);VD治疗组STAT-1和p-STAT-1蛋白表达较DN模型组降低,差异均有统计学意义(P <0.05)。DN模型组蛋白尿、血糖、血尿素氮和血清肌酐水平升高,差异均有统计学意义(P <0.05);VD治疗组蛋白尿、血尿素氮和血清肌酐水平较DN模型组降低,差异均有统计学意义(P <0.05)。DN模型组Ⅰ型胶原蛋白和纤连蛋白的mRNA表达较对照组升高,差异均有统计学意义(P <0.05);VD治疗组Ⅰ型胶原蛋白和纤连蛋白的mRNA表达较DN模型组降低,差异均有统计学意义(P <0.05)。DN模型组肾小球和肾间质巨噬细胞浸润较对照组增加,差异均有统计学意义(P <0.05);VD治疗组肾小球和肾间质巨噬细胞浸润较DN模型组减少,差异均有统计学意义(PObjective To explore the mechanism by which active vitamin D(VD) regulates the phenotypic activation of M1/M2 macrophages through the signal transducer and activator of transcription-1(STAT-1)-triggering receptor expressed on myeloid cells-1(TREM-1)pathway to alleviate renal interstitial fibrosis in diabetic nephropathy(DN). Methods Forty-five healthy male SD rats were divided into control group,DN model group and VD treatment group according to the random number table method,each group15 rats. Normal fed rats were used as control group. Diabetic rats were established in DN model group and VD treatment group. VD treatment group was given daily oral VD with a dose of 0. 1 μg/kg after the establishment of diabetes model. The rats were sacrificed at the 18th week. Blood samples were collected to measure biochemical parameters and kidneys were collected for histological and molecular examination. Stat-1 and P-STAT-1 protein expression were detected by Western blotting. Blood glucose,blood urea nitrogen and serum creatinine were analyzed by automatic biochemical analyzer. The mRNA expression of type Ⅰ collagen and fibronectin in rat kidney tissue was detected by RT-PCR. The infiltration of CD68 macrophages in glomerulus and interstitium of rats was analyzed by immunohistochemistry. The protein expression of CD163 and CD68 in rat kidney was analyzed by Western blotting. The concentrations of cytokines tumor necrosis factor alpha(TNF-α),inducible nitric oxide synthase(iNOS),Arg-1 and MR secreted by macrophages in glomerulus and interstitium of rats were analyzed by RT-PCR. Results The protein expression of STAT-1 and p-STAT-1 in the DN model group were higher than those in the control group,the differences were statistically significant(P < 0. 05);and the protein expression of STAT-1 and p-STAT-1 in the VD treatment group were lower than those in the DN model group,the differences were statistically significant(P < 0. 05). The histoneuria,blood sugar,blood urea nitrogen and serum creatinine levels of the DN model in

关 键 词：糖尿病肾病 活性维生素D STAT-1-TREM-1 M1/M2巨噬细胞表型 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]