人脐带间充质干细胞对大鼠重症急性胰腺炎的保护作用

Protective effect of human umbilical cord-derived mesenchymal stem cells against severe acute pancreatitis in rats

目的研究人脐带间充质干细胞(ucMSCs)对大鼠重症急性胰腺炎(SAP)的保护作用。方法 135只雄性SD大鼠随机分成对照组(Sham组),SAP组和SAP+ucMSCs组,每组45只。采用5%牛磺胆酸钠(0.1ml/100g)逆行胰管注射的方法制作大鼠SAP模型,SAP+ucMSCs组通过尾静脉注射CM-Di I标记的ucMSCs(1×10~7个/kg)。各组于术后12、24、72h处死取材,统计大鼠死亡率,HE染色观察各组胰腺组织病理学改变并评分,荧光显微镜观察ucMSCs定植情况,ELISA法测定大鼠血清淀粉酶和脂肪酶、肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、白介素4(IL-4)和白介素10(IL-10)的表达情况。结果 ucMSCs可定植在胰腺组织的损伤区域,可降低72h SAP大鼠的死亡率(SAP组为66.7%,SAP+ucMSCs组为20.0%)。ucMSCs移植后大鼠各时间点血清淀粉酶和脂肪酶水平明显降低(P<0.01),胰腺组织病理学评分、炎性因子TNF-α、IL-1β水平明显降低,抗炎因子IL-4、IL-10水平明显升高(P<0.05或P<0.01)。结论人脐带间充质干细胞移植治疗可减轻重症急性胰腺炎的胰腺组织损伤和炎症程度。

Objective To study the protective effects of human umbilical cord-derived mesenchymal stem cells （ucMSCs） against severe acute pancreatitis （SAP） in rats. Methods A total of 135 Sprague-Dawley male rats were randomly divided into Sham group, SAP group and SAP＋ucMSCs group （45 each）. SAP＋ucMSCs group： Severe acute pancreatitis was induced by injecting 5% sodium taurocholate （0.1ml/100g） into the common bilio-pancreatic duct and then CM-Dil-labeled ucMSCs at 1 × 10^7cells/kg were injected via the tail vein. All the rats were sacrificed 12, 24 and 72 hours after SAP. The 72h death rate was counted. Pathological changes in the pancrease were detected by HE staining and pathological score was graded, ucMSCs colonization was observed by fluorescence microscopy. The serum levels of amylase, lipase, TNF-α IL-1β, IL-4 and IL-10 were determined by ELISA. Results ucMSCs colonize the injured area of pancreatic tissue, the 72h death rate was reduced, and the serum amylase and lipase were also reduced significantly. Moreover, ucMSCs significantly reduced the pathological score of the pancrea and the level ofproinflammatory cytokines （TNF-α and IL-1β）, but the levels of anti-inflammatory cytokines were increased （IL-4 and IL-10）. Conclusion Transplantation of ucMSCs can reduce the severity of pancreatic injury and inflammation in SAP rats.