论著

炎症性肠病与 IgA 肾病共病特征基因及信号通路激活模式的整合分析

Integrated analysis of shared signature genes and signaling pathway activation patterns between inflammatory bowel disease and IgA nephropathy

:46-55
 
      目的   免疫球蛋白A肾病(IgAN)与炎症性肠病(IBD)的相互作用机制尚未阐明。本研究旨在解析IBD与IgAN共病的关键特征基因及核心信号通路,以揭示肠-肾轴的分子调控网络。方法   于GEO数据库获取IBD(GSE75214)和IgAN(GSE93798)基因表达谱,筛选差异表达基因(DEGs)。通过蛋白互作网络(PPI)和拓扑算法(MCC、MNC、Degree、EPC等)识别核心特征基因,并结合公共数据库(CTD、DISEASES和GeneCards)和单细胞转录组测序(GSE171314)进行验证。通过Nephroseq数据库验证基因表达与临床表型的相关性。结果   共筛选出17个IBD-IgAN共病DEGs,PPI网络分析等确定以FOS、EGR1、CXCL2JUNB为核心特征基因。功能富集分析显示白细胞介素-17(IL-17)信号通路显著激活。单细胞测序验证FOS、EGR1、CXCL2JUNB基因在IgAN特异性高表达,并通过Nephroseq数据库验证其与尿蛋白和估算的肾小球滤过率下降(eGFR)显著相关。结论  本研究揭示IBD与IgAN共享IL-17通路异常激活及FOS、EGR1、CXCL2JUNB的基因网络,为开发基于肠-肾轴调控的靶向治疗策略提供理论依据。
       Objective  The complex interplay between immunoglobulin A nephropathy(IgAN)and inflammatory bowel disease(IBD)remains poorly understood.This  study  aimed to identify  key  cross-talk  genes  and  pivotal  signaling pathways shared between IBD and IgAN,thereby elucidating the molecular regulatory network underlying the gut-kidney axis.Methods  Transcriptomic datasets for IBD(GSE75214)and IgAN(GSE93798)were retrieved from the GEO database.Differentially expressed genes(DEGs)were screened,and shared DEGs were intersected.Protein-protein interaction(PPI)networks were constructed using STRING and Cytoscape,with topological algorithms applied to identify hub genes.Gene expression profiles were validated through(CTD,DISEASES and GeneCards)and single-cell RNA sequencing(GSE171314)and the Nephroseq database,focusing on clinical correlations with proteinuria and estimated glomerular filtration rate(eGFR).Results  Seventeen shared DEGs were identified between IBD and IgAN.PPI network analysis revealed FOS,EGR1,CXCL2 and JUNB as core hub genes.Functional enrichment analysis demonstrated significant activation of the interleukin-17(IL-17)signaling pathway.Single-cell sequencing confirmed the specific upregulation of these genes in renal tubular epithelial cells of IgAN patients,which was further validated to correlate with proteinuria and eGFR decline.Conclusions  IBD and  IgAN share aberrant activation of the IL-17 pathway and a co-regulatory gene network involving FOS,EGR1,CXCL2 and JUNB,providing a theoretical foundation for developing therapeutic strategies centered on the gut-kidney axis.
论著

百令胶囊辅助缬沙坦治疗IgA肾病及对肾功能、Th1/Th2漂移、尿PCX、B7-1水平的影响

Effects of Bailing capsules assisting valsartan in the treatment of IgA nephropathy and its influence on renal function, Th1/Th2 drift, urine PCX and B7-1 levels

:46-49
 
目的 观察百令胶囊辅助缬沙坦治疗IgA肾病效果及对患者肾功能、细胞免疫调节、尿足细胞标志蛋白的影响。方法 选取2019年5月—2021年5月西部战区总医院肾内科收治经肾活检确诊为IgA肾病,筛选治疗方案中尚未使用激素及免疫抑制剂的80例患者,按住院先后顺序随机分为观察组和对照组,每组各40例。对照组给予缬沙坦治疗,观察组给予百令胶囊辅助缬沙坦治疗,治疗12周后,比较2组的疗效、治疗前后肾功能指标[24 h蛋白尿(24 h Upro)、尿素氮(BUN)、血肌酐(SCr)、尿红细胞(RBC)计数]、1型/2型辅助性T细胞(Th1/Th2)代表细胞因子[γ-干扰素(IFN-γ)、白介素-4(IL-4)]、尿足细胞标志蛋白[尿足萼糖蛋白(PCX)、尿足细胞B7-1分子(B7-1)]水平。结果 治疗12周后,观察组的治疗总有效率为95.0%,高于对照组的82.5%;观察组的24 h Upro、BUN、SCr、尿RBC计数低于对照组,IFN-γ、Th1/Th2低于对照组、IL-4高于对照组,尿PCX、B7-1水平低于对照组;差异均有统计学意义(P<0.05)。结论 百令胶囊辅助缬沙坦治疗IgA肾病患者,可以提高临床疗效,有效保护患者肾功能,调节其免疫状态,减轻肾损伤。
Objective To observe the effects of Bailing capsules assisting valsartan in the treatment of IgA nephropathy and its influence on renal function, cellular immune regulation and urine prodocytes marker protein. Methods From May 2019 to May 2021, 80 patients with IgA nephropathy confirmed by renal biopsy in the Nephrology Department of Western Theatre Command General Hospital, who had not used hormones or immunosuppressants in the treatment were selected.Patients were divided into observation group and control group according to the order of hospitalization, 40 cases in each group.The control group was given valsartan, and the observation group was given Bailing capsules and valsartan.After 12 weeks of treatment, the efficacy, the levels of renal function indexes [24 h proteinuria (24 h Upro), urea nitrogen (BUN), serum creatinine (SCr), urinary red blood cell (RBC) count], type 1/type 2 helper T cells (Th1/Th2) represent cytokines [interferon-γ (IFN-γ), interleukin-4 (IL-4)], urine prodocytes marker protein [urine podocalyxin (PCX), urinary podocyte B7-1 molecule (B7-1)] before and after treatment were compared between the two groups. Results After treatment, the total effective rate in observation group was higher than that in control group (95.0% vs 82.5%).The 24 h Upro, BUN, SCr levels and urine RBC count in observation group were lower than those in control group, IFN-γ and Th1/Th2 levels were lower than those in control group, the IL-4 level was higher than that in control group, and the levels of urine PCX and B7-1 were lower than those in control group.Those differences were statistically significant (P<0.05). Conclusions Bailing capsules assisting valsartan in the treatment of IgA nephropathy can improve clinical efficacy, effectively protect the renal function of patients, regulate the immune status, and alleviate renal injury.
论著

羟氯喹联合半量激素与足量激素治疗IgA肾病的比较

Comparison of hydroxychloroquine combined with half-dose glucocorticoid and full-dose glucocorticoid in the treatment of IgA nephropathy

:39-45
 
目的 对比羟氯喹联合半量激素与足量糖皮质激素(激素)治疗IgA肾病在减少尿蛋白、保护肾功能方面的效果以及不良反应的发生率。方法 筛选2020年6月—2022年1月我院收治基线尿蛋白排泄量>1 g/ d、基线估算肾小球滤过率>15 mL/min的IgA肾病患者为研究对象,随机分为羟氯喹+半量激素(Q+G)组及足量激素(G)组。Q+G组予羟氯喹及泼尼松0.5 mg/(kg·d),G组予泼尼松 1 mg/(kg·d),比较2组在治疗2、4、6个月后24 h尿蛋白定量的改变值;比较2组6个月内24 h尿蛋白较基线下降>30%的比例、24 h尿蛋白定量下降至1 g以下的比例、估算肾小球滤过率下降>30%的比例以及不良反应发生率。结果 纳入Q+G组49例,G组46例。2组在治疗2、4、6个月后的24 h尿蛋白定量改变值、6个月内24 h尿蛋白较基线下降>30%的比例、24 h尿蛋白定量下降至1 g以下的比例、6个月内估算肾小球滤过率下降>30%的比例比较差异均无统计学意义(均P>0.05);Q+G组不良反应发生率低于G组(P<0.05)。结论 与足量激素治疗相比,羟氯喹联合半量激素治疗尿蛋白持续>1 g/d的IgA肾病患者在减少尿蛋白、保护肾功能中的效果相近,而不良反应的发生率较低。
Objective Compared with full-dose glucocorticoid,to evaluate the effect of hydroxychloroquine combined with half-dose glucocorticoid in the treatment of IgA nephropathy in reducing urinary protein and protecting renal function,as well as the incidence of adverse reactions. Methods From June 2020 to January 2022,patients with IgA nephropathy whose baseline urinary protein excretion>1 g/d and baseline estimate glomerular filtration rate>15 mL/min were enrolled and randomly divided into hydroxychloroquine combined with half-dose glucocorticoid(Q+G)group and full-dose glucocorticoid(G)group. Each patient in Q+G group was given oral hydroxychloroquine and oral prednisone at a dose of 0. 5 mg/(kg·d). Each patient in G group was given prednisone at a dose of 1 mg/(kg·d). The changes in 24-hour urine protein quantification between the two groups at 2,4 and 6 months of treatment were compared;the proportions of 24-hour urine protein decreased by more than 30%,24-hour urine protein decreased to less than 1 g,estimate glomerular filtration rate decreased >30% and adverse reactions within 6 months were compared between the two groups. Results Fourty-nine cases were enrolled in Q+G group and 46 cases in G group. There was no significant difference in the 24-hour urine protein changes between the two groups at 2,4 and 6 months of treatment. The proportion of 24-hour urine protein decreased by 30%,the proportion of the 24-hour urine protein decreased to below 1 g and the proportions of patients whose estimate glomerular filtration rate decreased by >30% within 6 months between the two groups were not significantly different. The proportion of adverse reactions in Q+G group was lower than that in G group. Conclusions Hydroxychloroquine combined with half-dose glucocorticoid has similar effects in reducing urinary protein and protecting renal function and lowering incidence of adverse reactions compared with full-dose glucocorticoid therapy in the treatment of patients with IgA nephropathy whose urinary protein excretion > 1 g/d.
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