■脾肿大可加剧肝硬化和门脉高压。我们先前已经证明环氧合酶-2(COX-2)抑制剂可以减轻肝硬化脾肿大。然而,肝硬化脾肿大的机制尚不清楚,从而成为本研究的重点。
■硫代乙酰胺(TAA)腹腔注射诱导肝硬化脾肿大。大鼠随机进入对照组,TAA和TAA+塞来昔布基团。对脾脏进行组织学分析和高通量RNA测序。脾胶原III,α-SMA,对Ki-67和VEGF进行定量。
■与对照组相比,在TAA组的脾脏中鉴定出总共1461个差异表达基因(DEGs)。免疫应答和免疫细胞活化可能是参与肝硬化脾肿大发病的主要信号通路。凭借其免疫调节作用,塞来昔布可改善肝硬化脾肿大和肝硬化。此外,在TAA与对照和TAA+塞来昔布vs.TAA。基因本体论(GO)和KEGG分析共同表明,塞来昔布可能通过抑制脾免疫细胞增殖来减轻肝硬化脾肿大。炎症,免疫调节,和纤维生成。对这些因素的影响随后通过减少的脾Ki-67阳性细胞来验证,巨噬细胞,纤维化区域,胶原蛋白III和α-SMA的mRNA水平。
■塞来昔布通过抑制脾免疫细胞增殖减弱肝硬化脾肿大,炎症,和纤维生成。当前的研究通过靶向脾异常来阐明肝硬化的治疗策略,并提供COX-2抑制剂作为肝硬化脾肿大的新型药物治疗。
UNASSIGNED: Splenomegaly can exacerbate liver cirrhosis and portal hypertension. We have previously demonstrated that cyclooxygenase-2 (COX-2) inhibitor can attenuate cirrhotic splenomegaly. However, the mechanism of cirrhotic splenomegaly remains unclear, thus becoming the focus of the present study.
UNASSIGNED: Thioacetamide (TAA) intraperitoneal injection was used to induce cirrhotic splenomegaly. Rats were randomized into the control, TAA and TAA + celecoxib groups. Histological analysis and high-throughput RNA sequencing of the spleen were conducted. Splenic collagen III, α-SMA, Ki-67, and VEGF were quantified.
UNASSIGNED: A total of 1461 differentially expressed genes (DEGs) were identified in the spleens of the TAA group compared to the control group. The immune response and immune cell activation might be the major signaling pathways involved in the pathogenesis of cirrhotic splenomegaly. With its immunoregulatory effect, celecoxib presents to ameliorate cirrhotic splenomegaly and liver cirrhosis. Furthermore, 304 coexisting DEGs were obtained between TAA vs. control and TAA + celecoxib vs. TAA. Gene ontology (GO) and KEGG analyses collectively indicated that celecoxib may attenuate cirrhotic splenomegaly through the suppression of splenic immune cell proliferation, inflammation, immune regulation, and
fibrogenesis. The impacts on these factors were subsequently validated by the decreased splenic Ki-67-positive cells, macrophages, fibrotic areas, and mRNA levels of collagen III and α-SMA.
UNASSIGNED: Celecoxib attenuates cirrhotic splenomegaly by inhibiting splenic immune cell proliferation, inflammation, and
fibrogenesis. The current study sheds light on the therapeutic strategy of liver cirrhosis by targeting splenic abnormalities and provides COX-2 inhibitors as a novel medical treatment for cirrhotic splenomegaly.