Gong Jian, Xiong Zhaoming, Yu Weidi, Song Zhenshun
Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 200072, Shanghai, China.
Department of General Surgery, Shanghai Fourth People's Hospital, Tongji University School of Medicine, 200072, Shanghai, China.
Dig Dis Sci. 2024 Jan;69(1):135-147. doi: 10.1007/s10620-023-08189-5. Epub 2023 Nov 26.
Acute severe pancreatitis (SAP) is a severe acute abdominal disease, which can lead to pancreatic infection and necrosis as well as distant organ damage. Bone marrow mesenchymal stem cells (BMSCs) can exert anti-inflammatory effect on SAP, while NLRP3 inflammasomes play an important role in the inflammatory response. This study aimed to investigate whether BMSCs exert anti-inflammatory effect on SAP by inhibiting NLRP3 inflammasome.
The rat SAP model was established. Serum amylase, lipase and inflammatory factor levels were measured by ELISA, and the level of tissue injury was assessed by HE staining. The expression of NLRP3 inflammasome was detected by PCR, Western Blot and immunohistochemistry. ML385 was used to block Nrf2 pathway, aiming to investigate whether Nrf2 pathway was involved in the therapeutic effect of BMSCs on SAP by regulating NLRP3 inflammasome expression.
In SAP rats, NLRP3 inflammasome was activated, which became more evident over time. After transplantation of BMSCs, the NLRP3 inflammasome expression decreased at both mRNA and protein levels, the serum levels of amylase, lipase and inflammatory factors decreased, and the pathological scores of the pancreas and lung were both improved. After blocking the Nrf2 pathway, the NLRP3 inflammasome expression increased in the injured pancreas and lung, and the inflammation deteriorated, which inhibited the therapeutic effects of BMSCs on SAP.
The therapeutic effect of BMSC on SAP is at least partially ascribed to the inhibition of NLRP3 inflammasome, and Nrf2 pathway mediates the therapeutic effect of BMSC on SAP by inhibiting NLRP3 inflammasome.
急性重症胰腺炎（SAP）是一种严重的急性腹部疾病，可导致胰腺感染、坏死以及远处器官损伤。骨髓间充质干细胞（BMSCs）可对SAP发挥抗炎作用，而NLRP3炎性小体在炎症反应中起重要作用。本研究旨在探讨BMSCs是否通过抑制NLRP3炎性小体对SAP发挥抗炎作用。
建立大鼠SAP模型。采用酶联免疫吸附测定法（ELISA）检测血清淀粉酶、脂肪酶及炎性因子水平，通过苏木精-伊红（HE）染色评估组织损伤程度。采用聚合酶链反应（PCR）、蛋白质免疫印迹法（Western Blot）及免疫组织化学法检测NLRP3炎性小体的表达。使用ML385阻断Nrf2通路，旨在研究Nrf2通路是否通过调节NLRP3炎性小体表达参与BMSCs对SAP的治疗作用。
在SAP大鼠中，NLRP3炎性小体被激活，且随时间推移愈发明显。BMSCs移植后，NLRP3炎性小体在mRNA和蛋白质水平的表达均降低，血清淀粉酶、脂肪酶及炎性因子水平降低，胰腺和肺的病理评分均得到改善。阻断Nrf2通路后，受损胰腺和肺中NLRP3炎性小体表达增加，炎症恶化，抑制了BMSCs对SAP的治疗作用。
BMSCs对SAP的治疗作用至少部分归因于对NLRP3炎性小体的抑制，且Nrf2通路通过抑制NLRP3炎性小体介导BMSCs对SAP的治疗作用。
