摘要
目的研究胎盘间充质干细胞(placenta-derived mesenchymal stem cells,P-MSCs)对大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)的保护作用。方法健康成年雄性SD大鼠32只,随机分为对照组、P-MSCs组、SAP组和SAP+P-MSCs组,每组8只。采用4%牛磺胆酸钠胆胰管逆行注射法建立SAP大鼠模型,造模结束后12 h与36 h经尾静脉注射P-MSCs(1×10^6个/100 g)。大鼠在P-MSCs第一次输注后72 h处死,HE染色评估胰腺损伤程度,ELISA法测定血清中炎症因子、淀粉酶与脂肪酶浓度,qRT-PCR检测胰腺组织中炎症因子基因表达水平,免疫组化法检测胰腺组织中巨噬细胞浸润情况。结果体外输注的P-MSCs有向损伤部位定植的特性。与SAP组相比,SAP+P-MSCs组胰腺病理评分明显降低(P<0.05);血清中淀粉酶、脂肪酶、IL-1β、IL-6与TNF-α浓度明显降低(P<0.05),而IL-10、IL-4和TGF-β浓度明显升高(P<0.05);胰腺组织中IL-1β与TNF-αmRNA表达水平明显降低(P<0.05),IL-10与IL-4 mRNA表达水平明显升高(P<0.05)。此外,P-MSCs可以有效减轻胰腺组织中巨噬细胞浸润。结论P-MSCs能有效减轻SAP大鼠胰腺局部炎症反应与全身炎症反应,其减轻胰腺局部炎症反应可能与其减少胰腺局部巨噬细胞与中性粒细胞浸润有关。
Objective To investigate the protective effects of human placenta-derived mesenchymal stem cell(P-MSC)transplantation against severe acute pancreatitis(SAP)in rats.Methods A total of 32 healthy adult male Sprague-Dawley(SD)rats were randomly divided into control group,P-MSC group,SAP and SAP+P-MSCs group(n=8),and in the latter 2 groups,SAP was induced by retrograde injection of 4% sodium taurocholate into the common biliopancreatic duct.P-MSCs(1×10^6 cells/100 g)were delivered through the tail vein of the rats at 12 and 36 h after the induction of SAP.All the rats were sacrificed 72 h after the first P-MSC infusion.HE staining was used to assess the pancreatic pathologies of the rats after the treatments.The serum levels of the pro-and anti-inflammatory mediators,amylase and lipase were determined by ELISA,and the mRNA expression levels of the inflammatory mediators in the pancreatic tissue were detected using qRT-PCR.Immunohistochemistry was performed to examine macrophage infiltration in the pancreatic tissue of the rats.Results Homing of the infused P-MSCs to the injury site was observed in the rats with SAP.Transplantation of P-MSCs significantly ameliorated histopathological injury and lowered pancreatic pathological score of the pancreas,reduced serum levels of amylase,lipase,interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)(P<0.05),increased serum levels of IL-10,IL-4 and transforming growth factor-β(TGF-β)(P<0.05),decreased the expression levels of IL-1βand TNF-α(P<0.05)and increased the expression of IL-10 and IL-4 in the pancreatic tissue(P<0.05)of the rats with SAP.In addition,P-MSC transplantation effectively reduced macrophage infiltration in the pancreatic tissue of the rats.Conclusion Transplantation of P-MSCs can effectively alleviate local inflammatory response in the pancreas and systemic inflammatory response in rats with SAP probably by reducing local macrophage and neutrophil infiltration in the pancreas.
作者
黄启林
杨屹
罗晨
李帅
汤礼军
孙红玉
HUANG Qilin;YANG Yi;LUO Chen;LI Shuai;TANG Lijun;SUN Hongyu(College of Medicine,Southwest Jiaotong University,Chengdu,610031,Sichuan Province;Key Laboratoiy of Pancreatic Injury and Repair of Sichuan Province,General Hospital of Western Theater Conunand,Chengdu,610083,Sichuan Province,China)
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2020年第7期646-655,共10页
Journal of Third Military Medical University
基金
国家自然科学基金面上项目(81772001)
国家临床重点专科建设项目(41792113)。
关键词
间充质干细胞
移植
重症急性胰腺炎
胎盘
巨噬细胞
mesenchymal stem cells
transplantation
severe acute pancreatitis
placenta
macrophages
