糖尿病肾病小鼠中前纤维蛋白1的表达和免疫细胞浸润分析  

Expression of profilin 1 and immunocyte infiltration in diabetic nephropa thy mice

作　　者：麦丽萍 黄桂萍 邓春玉 郑丹琳 李晓红 何国东 MAI Liping;HUANG Guiping;Deng Chunyu;ZHENG Danlin;LI Xiaohong;HE Guodong(Medical Research Institute,Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences),SouthernMedical University,Guangzhou 510080,China)

机构地区：[1]南方医科大学附属广东省人民医院(广东省医学科学院)医学研究部,广东广州510080

出　　处：《中国病理生理杂志》2024年第3期484-492,共9页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.82170259);广东省医学科学技术研究基金(No.A2023034)。

摘　　要：目的:探讨前纤维蛋白1(profilin 1,PFN1)在糖尿病肾病小鼠中的表达及其与免疫细胞浸润的相关性。方法:利用糖尿病肾病患者肾组织芯片转录组表达数据分析PFN1的表达水平和免疫细胞浸润情况,并通过小鼠动物实验进行验证。将16只C57BL/6小鼠随机分为正常组和模型组,每组8只。模型组采用腹腔注射链脲佐菌素法建立糖尿病肾病小鼠模型,造模成功后检测小鼠肾组织中CD11b、F4/80、CC趋化因子受体4(CC chemo kine receptor 4,CCR4)、白细胞介素1受体I型(interleukin-1 receptor type I,IL-1R1)、B细胞淋巴瘤2(B-cell lympho ma-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2-associated X protein,Bax)和胱天蛋白酶3(caspase-3)蛋白的表达水平。另外,在糖尿病肾病细胞模型中过表达PFN1,检测单核细胞趋化蛋白1(monocyte chemotactic protein-1,MCP-1)和cas pase-3蛋白的表达情况。结果:糖尿病肾病患者肾组织芯片转录组表达数据集GSE30122中,PFN1基因表达量显著升高(P<0.01),且与巨噬细胞和T细胞有显著相关性。糖尿病肾病小鼠模型组肾脏组织可见明显病理改变,肾脏组织中PFN1表达量显著升高(P<0.01),免疫指标CD11b、F4/80、CCR4、IL-1R1和凋亡相关蛋白Bax、Bcl-2、cas pase-3表达升高(P<0.01)。过表达PFN1可促进MCP-1和caspase-3蛋白的表达。结论:糖尿病肾病小鼠肾组织中可见巨噬细胞和Th17免疫细胞浸润且PFN1表达上调,促进糖尿病肾病细胞凋亡。AIM:The objective of this study is to examine the expression of profilin 1(PFN1)in mice with di abetic nephropathy and determine its association with immune cell infiltration.METHODS:This study presents an analy sis of PFN1 expression and immune cell infiltration in patients with diabetic nephropathy,utilizing transcriptome expres sion data from kidney tissue microarray.Additionally,the findings were validated in a diabetic nephropathy mouse model.Sixteen C57BL/6 mice were randomly assigned into two groups,namely the normal group and the model group,in an equal manner.The model group underwent the establishment of the diabetic nephropathy model through intraperitoneal injection of streptozotocin.Subsequently,the expression levels of CD11b,F4/80,CC chemokine receptor 4(CCR4),interleukin-1 receptor type I(IL-1R1),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-3 in kidney tissue were assessed upon successful establishment of the diabetic nephropathy model.Furthermore,the overexpression of PFN1 was observed in a cellular model of diabetic nephropathy,and the protein expression levels of monocyte chemotactic pro tein-1(MCP-1)and caspase-3 were assessed.RESULTS:The expression of PFN1 was found to be significantly in creased in the GSE30122 dataset of transcriptome expression in kidney tissues affected by diabetic nephropathy(P<0.01).This increase in PFN1 expression was found to be correlated with the presence of macrophages and T cells.Fur thermore,the renal tissue of the diabetic nephropathy model group exhibited significant pathological changes.In this mod el group,the expression levels of PFN1,CD11b,F4/80,CCR4,IL-1R1,Bax,Bcl-2,and caspase-3 were all significant ly increased(P<0.01).Overexpression of PFN1 could enhance the expression of MCP-1 and caspase-3 proteins.CON CLUSION:Macrophages and Th17 cells were identified within the renal tissue of mice with diabetic nephropathy,con comitant with an up-regulation in the expression of PFN1.This up-regulation was observed to facilitate the induction o

关 键 词：前纤维蛋白1 糖尿病肾病 细胞免疫浸润 细胞凋亡 

分 类 号：R587.2[医药卫生—内分泌] R363.2[医药卫生—内科学] R392.32[医药卫生—临床医学]