Protective effects of bone marrow mesenchymal stem cells transplantation and mobilization for severe acute pancreatitis with acute renal injury / 中华消化外科杂志

ABSTRACT

Objective To investigate the protective effects of bone marrow mesenchymal stem cells transplantation (MSCT) and mobilization on severe acute pancreatitis (SAP) with acute renal injury.Methods A total of 240 SD rats were randomly divided into sham operation group ( n =48 ),model control group ( n =48 ),MSCT group ( n =48),bone marrow mesenchymal stem cells mobilization (MSCM) group ( n =48) and MSCT +MSCM group ( n =48 ) according to the random number table.Rat models of SAP were made by peritoneal injection of L-arginine.Rats in the MSCT group were injected with 1.2 ml of bone marrow mesenchymai stem cells via femoral vein at 6 hours after SAP model establishment; rats in the MSCM group were subcutaneously injected with 40 μg/kg of granulocyte-colony stimulating factor (G-CSF) at 3 days before SAP model establishment; rats in the MSCT + MSCM group were injected with 1.2 ml of MSC and 40 μg/kg of G-CSF simultaneously; rats in the sham operation group were injected with equal volume of normal saline.According to different time points after operation,rats in each group were subdivided into 12 h,24 h,48 h and 72 h groups (n =12).At each time points after operation,the mortality rate,pathological changes of renal tissue,expression of Bax protein,Bcl-2 protein and apoptosis indexes of renal tubular epithelium cells were observed.The contents of tumor necrotic factor-α (TNF-α),interleukin-6 (IL-6),blood urea nitrogen (BUN),creatinine (Cr),lactate dehydrogenase (LDH) and C-reactive protein (CRP) were determined.All data were analyzed by using SNK-q test,Fisher exact probability and analysis of variance.Results All rats in the sham operation group were survived.The numbers of rats in the model control group survived at postoperative 48 hours and 72 hours were 11 and 8,respectively.No rat died at postoperative 48 hours in the MSCT group,MSCM group and MSCT + MSCM group.The numbers of rats survived at postoperative 72 hours in the MSCT group,MSCM group and MSCT + MSCM group were 11,10 and 11,which were not significantly different from the number of survived rats in the model control group (P ＞0.05).The pathological injuries of renal tissues were relieved in the MSCT group,MSCM group and MSCT + MSCM group when compared with model control group.The expression of Bax protein,Bc1-2 protein,renal tubular epithelium cell apoptosis indexes at 12-72 hours were 12.80 + 1.78-20.30 + 2.40,4.34 + 1.20-3.03 ± 1.06,12.65％ ±2.31％-35.10％ ± 5.54％ in the model control group,9.68 ± 2.11-17.01 ± 2.54,5.57 ± 1.35-4.13 + 1.05,6.20％ ± 1.53％- 17.50％ ± 2.80％ in the MSCT group,10.05 ± 2.17-16.81 ± 2.55,5.49 ± 1.48-4.19 ±1.05,6.41％± 1.64％-17.14％±2.27％ in the MSCM group,8.33 ±2.06-14.03 ±2.27,6.60 ±2.11-5.63 ±1.52,5.80％ ± 1.52％-12.30％ ±2.43％ in the MSCT + MSCT group.There were significant differences in the expressions of Bax protein at 24 and 72 hours,Bcl-2 protein at 48 and 72 hours,renal tubular epithelium cell apoptosis index at 24,48 and 72 hours between the MSCT group,MSCM group and MSCT + MSCM group ( P ＜0.05 ),but no significant difference was found between the MSCT group and the MSCM group ( P ＞ 0.05 ).The contents of TNF-α,IL-6,BUN,Cr,LDH,CRP in the MSCT group,MSCM group and MSCT + MSCM group were decreased when compared with those in the model control group,and a significant decrease of the 6 factors was observed in the MSCT + MSCM group.There were significant difference in the content of TNF-α at 72 hours,IL-6,BUN and Cr at 48 and 72 hours,LDH at 24,48 and 72 hours and CRP at 72 hours between the MSCT group,MSCM group and MSCT + MSCM group (P ＜0.05),while no significant difference was observed between the MSCT group and the MSCM group (P ＞ 0.05).Conclusion MSCT and MSCM can significantly protect acute renal injury in the progress of SAP,the probable mechanisms are pathological regeneration,anti-inflammatory effect and apoptosis inhibition of mesenchymal stem cells.