孙良.人脐带间充质干细胞可减轻重症急性胰腺炎大鼠相关肝损伤[J].内科急危重症杂志,2025,31(1):72-76
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DOI:10.11768/nkjwzzzz20250114 |
中文关键词: 人脐带间充质干细胞 重症急性胰腺炎 肝损伤 NF κB TLR4 |
英文关键词: |
基金项目:山东省医药卫生科技发展计划项目(202002081180);山东省重点研发计划项目(2019GSF108249) |
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中文摘要: |
摘要 目的:观察人脐带间充质干细胞对重症急性胰腺炎(SAP)大鼠相关肝损伤的保护作用并探讨其可能的作用机制。方法:选取72只雄性Wistar大鼠随机分为假手术组(Sham组)、SAP模型组(SAP组)、激动剂组(SAP+LPS组)、抑制剂组(SAP+TAK-242组)、细胞干预组(SAP+huMSC组)和细胞+激动剂组(SAP+huMSC+LPS组),每组12只。HE染色观察大鼠胰腺及肝脏组织病变,检测血清淀粉酶、脂肪酶及丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)含量,采用酶联免疫吸附法检测血清肿瘤坏死因子(TNF-α)、白介素(IL)-6水平,采用免疫印迹试验和逆转录聚合酶链反应分别检测肝组织Toll样受体4(TLR4)、抗核因子-κB p65(NF-κB p65)蛋白及TNF-α、IL-6 mRNA的表达。结果:与Sham组比较,SAP组大鼠胰腺和肝脏可见明显的病理损伤,血清淀粉酶、脂肪酶、ALT、AST、TNF-α、IL-6水平明显升高(P均<0.05),肝组织TLR4、NF-κBp65蛋白及TNF-α、IL-6mRNA 的表达明显升高(P均<0.05);与SAP 组比较,SAP+TAK-242组和SAP +huMSC组大鼠胰腺和肝脏组织病理损伤减轻,上述指标的表达明显降低(P均<0.05),而SAP+LPS组以上指标升高(P均<0.05);与SAP+LPS组比较,SAP+huMSC+LPS组大鼠胰腺和肝脏组织病理损伤减轻,上述指标的表达明显降低(P均<0.05)。结论:人脐带间充质干细胞可减轻SAP大鼠相关肝损伤,其作用机制可能与抑制TLR4/NF-κB通路相关。 |
英文摘要: |
Abstract Objective: To observe the protective effect of human umbilical cord mesenchymal stem cells (huMSCs) on liver injury in rats with severe acute pancreatitis (SAP) and explore its possible mechanism. Methods: A total of 72 male Wistar rats were randomly divided into Sham group, SAP model group, agonist group (SAP+LPS group), inhibitor group (SAP+TAK-242 group), cell intervention group (SAP+huMSC group), and cell+agonist group (SAP+huMSC+LPS group), with 12 rats in each group. The pathological changes of pancreas and liver were observed by HE staining. Serum amylase, lipase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. The levels of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay. The expression of To11-like receptor 4 (TLR4), nuclear factor-κBp65 (NF-κBp65) protein, TNF-α and IL-6 mRNA in liver tissues were detected by Western blotting and reverse transcription polymerase chain reaction, respectively. Results: Compared with the Sham group, significant pathological damage was observed in the pancreas and liver of SAP group rats. The levels of serum amylase, lipase, ALT, AST, TNF-α and IL-6 were significantly increased (all P< 0.05). The expression levels of TLR4, NF-κBp65 protein, TNF-α and IL-6 mRNA in liver tissue were significantly increased (all P< 0.05). Compared with the SAP group, the pathological injury of pancreas and liver in SAP+TAK-242 group and SAP+huMSC group was alleviated, and the expression of above indicators was significantly decreased (all P< 0.05), while the above indicators were increased in SAP+LPS group (all P< 0.05). Compared with the SAP+LPS group, the pathological injury of pancreas and liver in SAP+huMSC+LPS group was decreased, and the expression of the above indicators was significantly decreased (all P< 0.05). Conclusion: HuMSCs can alleviate liver injury in SAP rats, and the mechanism might be related to inhibition of TLR4/NF-κB pathway. |
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