Zhang Xinyu, Li Zenghui, Liu Wei, Du Juanjuan, Liu Yun, Yu Ningjun, Liu Chao, Zeng Mei, Zhang Xiaoming
Medical Imaging Key Laboratory of Sichuan Province and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People's Republic of China.
Department of Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637000, People's Republic of China.
J Inflamm Res. 2022 Apr 13;15:2349-2363. doi: 10.2147/JIR.S351416. eCollection 2022.
Acute pancreatitis can be classified histologically as interstitial edema pancreatitis (IEP) or as acute necrotizing pancreatitis (ANP). ANP has a higher mortality and long-term or short-term sequelae than IEP. Therefore, this work aims to explore the differences in pathogenesis between ANP and IEP and it has great clinical importance for the treatment and prevention of ANP.
In this work, whole blood samples from IEP and ANP patients were analyzed by whole gene sequencing (WGS). Serum samples from IEP and ANP patients were evaluated via enzyme-linked immunosorbent assay (ELISA). Meanwhile, pancreatic tissues of IEP and ANP rat models were subjected to data independent acquisition (DIA) proteomics assays. Then, the WGS analysis and DIA proteomics assay data were analyzed comprehensively.
Six pathways were found to be significantly different in the ANP/IEP groups through WGS analysis. DIA proteomics found eleven different pathways. In both assays, the complement and coagulation cascades pathway was the most significantly different ( < 0.01) pathway between the two groups. WGS analysis showed base mutations in ten genes in the complement and coagulation cascades pathway. These results were consistent with the ten proteins detected by DIA proteomics analysis, which were significantly upregulated in the ANP/IEP groups. In addition, five of these proteins, complement C3, complement Factor I, alpha-2-macroglobulin, complement C9, and serpin family C member 1, were successfully verified by parallel reaction monitoring analysis and ELISA.
C3, CFI, Am, C9, and Serpinc1, which belong to complement and coagulation cascades pathway, may promote pancreatic necrosis and aggravate the severity of ANP.
急性胰腺炎在组织学上可分为间质性水肿性胰腺炎（IEP）或急性坏死性胰腺炎（ANP）。ANP的死亡率以及长期或短期后遗症均高于IEP。因此，本研究旨在探讨ANP与IEP发病机制的差异，这对ANP的治疗和预防具有重要的临床意义。
在本研究中，通过全基因测序（WGS）分析IEP和ANP患者的全血样本。采用酶联免疫吸附测定（ELISA）评估IEP和ANP患者的血清样本。同时，对IEP和ANP大鼠模型的胰腺组织进行数据非依赖采集（DIA）蛋白质组学分析。然后，对WGS分析和DIA蛋白质组学分析数据进行综合分析。
通过WGS分析发现ANP/IEP组中有6条通路存在显著差异。DIA蛋白质组学发现11条不同的通路。在这两种分析中,补体和凝血级联反应通路是两组之间差异最显著（P<0.01）的通路。WGS分析显示补体和凝血级联反应通路中有10个基因发生碱基突变。这些结果与DIA蛋白质组学分析检测到的10种蛋白质一致，它们在ANP/IEP组中显著上调。此外，其中5种蛋白质，即补体C3、补体因子I、α-2-巨球蛋白、补体C9和丝氨酸蛋白酶抑制剂家族C成员1，通过平行反应监测分析和ELISA成功得到验证。
属于补体和凝血级联反应通路的C3、CFI、Am、C9和Serpinc1可能促进胰腺坏死并加重ANP的严重程度。
