【摘要】 目的:研究骨髓间充质干细胞(bmMSCs)在重症急性胰腺炎(SAP)大鼠模型治疗中的应用。方法:经胆管逆行注射牛磺胆酸钠诱导形成大鼠SAP模型。将大鼠随机分为5组:对照组、SAP组、SAP+bmMSCs(尾静脉)组、SAP+bmMSCs(腹腔)组和SAP+bmMSCs(尾静脉+腹腔)组,每组18只。在bmMSCs注射各组,诱导SAP后3 h分别通过尾静脉、腹膜内和尾静脉加腹膜内途径注射用DAPI标记的bmMSCs。分别在实验开始后的第24、48、72 h分别处死6只大鼠,并收集胰腺组织和血液,测定其中血清抗炎细胞因子(IL-10)和炎症细胞因子(IL-1β、TNF-α、IL-6)的水平。光学显微镜下观察胰腺的病理变化,同时在荧光显微镜下检测DAPI标记的体内bmMSCs分布。结果:与对照组相比,SAP组大鼠的胰腺组织有明显的出血、水肿、炎症和坏死。与SAP组相比,3种方式bmMSCs移植组胰腺的炎症、水肿、出血和坏死均明显减少(P<0.05)。在3种方式bmMSCs移植组中,bmMSCs显著降低促炎细胞因子(TNF-α、IL-6和IL-1β)的水平,但是增加了SAP大鼠的抗炎细胞因子(IL-10)水平(P<0.05)。在SAP+bmMSCs(尾静脉+腹腔)移植组中,TNF-α、IL-6和IL-1β水平进一步降低,IL-10水平进一步升高(P<0.05);同时,在该组中观察到更多的bmMSCs存在。结论:与腹腔注射法相比,通过尾静脉+腹腔注射或尾静脉注射bmMSCs,可以观察到更多的bmMSCs存在于胰腺组织中,大鼠恢复的更好。更多还原

【Abstract】 Objective:To study the application of bone marrow mesenchymal stem cells(bmMSCs) in the treatment of severe acute pancreatitis(SAP) rat model. Methods:A rat model of SAP was induced by retrograde injection of sodium taurocholate into the bile duct. Rats were randomly divided into 5 groups:control group, SAP group, SAP+bmMSCs(tail vein) group, SAP+bmMSCs(intraperitoneal) group and SAP+bmMSCs(tail vein+intraperitoneal) group, with 18 rats in each group. Each group was injected with DAPI-labeled bmMSCs,and bmMSCs were injected through the tail vein, intraperitoneal and tail vein + intraperitoneal route 3 h after induction of SAP. Six rats were sacrificed at 24, 48, and 72 h after the start of the experiment, and pancreatic tissue and blood were collected. Serum anti-inflammatory cytokines(IL-10) and inflammatory cytokines(IL-1β, TNF-α, IL-6) were measured. The pathological changes of the pancreas were observed under a light microscope, and the distribution of bmMSCs in the DAPI markers was detected under a fluorescence microscope. Results:Compared with the control group, the pancreatic tissue of the SAP group had obvious bleeding, edema, inflammation and necrosis. Compared with the SAP group, the inflammation, edema, hemorrhage and necrosis of the pancreas in the three groups of bmMSCs transplantation group were significantly reduced(P<0.05). In three ways of bone marrow mesenchymal stem cell transplantation, bmMSCs significantly reduced levels of pro-inflammatory cytokines(TNF-α, IL-6 and IL-1β), but increased anti-inflammatory cytokines(IL-10) Level(P<0.05) in SAP rats. In the tail vein + intraperitoneal transplantation group, TNF-α, IL-6 and IL-1β levels were further decreased, and IL-10 levels were further increased(P<0.05). At the same time, more bmMSCs were observed in the tail vein + intraperitoneal transplant group. Conclusion:SAP rats injected with bmMSCs via the tail vein + intraperitoneally recovered better than by tail vein or intraperitoneal injection alone. More bmMSCs were observed in pancreatic tissue by tail vein + intraperitoneal injection compared to tail vein injection of bmMSCs or intraperitoneal injection.更多还原