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骨髓间充质干细胞移植对大鼠胰腺炎相关性肺损伤的保护作用。

Protective effect of transplanted bone marrow-derived mesenchymal stem cells on pancreatitis-associated lung injury in rats.

机构信息

Department of General Surgery, Fuzhou General Hospital of Nanjing Military Region, Fuzhou, Fujian 350025, PR China.

出版信息

Mol Med Rep. 2012 Aug;6(2):287-92. doi: 10.3892/mmr.2012.922. Epub 2012 May 21.

Abstract

Severe acute pancreatitis (SAP) is initiated by the premature activation of digestive enzymes within the pancreatic acinar cells, leading to self-digestion and inflammatory responses in pancreatic ductal cells, thus giving rise to systemic inflammatory response syndrome (SIRS). The most common and serious SIRS is pancreatitis-associated lung injury, and inflammatory mediators play an important role in its pathogenesis. Bone marrow-derived mesenchymal stem cells (MSCs) are differentiated into alveolar endothelial cells to replace the damaged alveolar endothelial cells and inhibit inflammatory response in the injured lung tissues. In this study, we aimed to investigate the therapeutic effect of bone marrow-derived MSCs in rats with pancreatitis-associated lung injury. Experimental SAP was induced by a retrograde injection of 5% sodium taurocholate into the biliopancreatic duct of 75 male Sprague-Dawley rats, which were divided into the SAP group (n=25), the MSC group (n=25) and the sham-operated group (n=25) to explore the pathology and function of lung tissues and the regulation of inflammatory mediators. Pulmonary edema was estimated by measuring water content in the lung tissues. Pulmonary myeloperoxidase (MPO) activity was detected using spectrophotometry. Serum amylase was detected using the Automatic Biochemistry Analyzer. Tumor necrosis factor-α (TNF-α) and substance P (SP) mRNA levels were determined by quantitative reverse transcriptase-polymerase chain reaction. Our results showed that serum amylase activity was significantly decreased in the MSC group compared to the SAP group. Pulmonary edema was significantly diminished (p<0.05) in the MSC group compared to the SAP group. Typical acute lung injury was observed in the SAP group, and the pathological changes were mild in the MSC group. The expression of TNF-α and SP mRNA in lung tissue was diminished in the MSC group compared to the SAP group. In conclusion, MSC transplantation attenuates pulmonary edema and inflammation, and reduces the mRNA expression of TNF-α and SP in pancreatitis-associated lung injury.

摘要

重症急性胰腺炎(SAP)是由胰腺腺泡细胞中消化酶的过早激活引起的,导致胰腺导管细胞的自我消化和炎症反应,从而引发全身炎症反应综合征(SIRS)。最常见和最严重的 SIRS 是胰腺炎相关的肺损伤,炎症介质在其发病机制中起重要作用。骨髓间充质干细胞(MSCs)分化为肺泡内皮细胞,以替代受损的肺泡内皮细胞,并抑制损伤肺组织中的炎症反应。在本研究中,我们旨在研究骨髓间充质干细胞在胰腺炎相关肺损伤大鼠中的治疗效果。通过逆行注射 5%牛磺胆酸钠到胰胆管,诱导 75 只雄性 Sprague-Dawley 大鼠产生实验性 SAP,将其分为 SAP 组(n=25)、MSC 组(n=25)和假手术组(n=25),以探讨肺组织的病理和功能以及炎症介质的调节。通过测量肺组织中的含水量来估计肺水肿。用分光光度法检测肺髓过氧化物酶(MPO)活性。用自动生化分析仪检测血清淀粉酶。采用定量逆转录-聚合酶链反应(qRT-PCR)测定肿瘤坏死因子-α(TNF-α)和 P 物质(SP)mRNA 水平。我们的结果表明,与 SAP 组相比,MSC 组的血清淀粉酶活性显著降低。与 SAP 组相比,MSC 组的肺水肿明显减少(p<0.05)。SAP 组可见典型的急性肺损伤,MSC 组的病理变化较轻。与 SAP 组相比,MSC 组肺组织中 TNF-α和 SP mRNA 的表达减少。综上所述,MSC 移植可减轻胰腺炎相关肺损伤的肺水肿和炎症,并降低 TNF-α和 SP mRNA 的表达。

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