MSC移植治疗SAP大鼠失败的原因探讨

Reasons of Failure for MSC Transplantation Treatment to SAP Rats

目的研究MSC移植治疗SAP大鼠的效果,探讨治疗失败的原因。方法将雄性SD大鼠随机分成5组:假手术组(SO组)、重症急性胰腺炎组(SAP组)、地塞米松治疗组(D组)、干细胞治疗组(M组)和干细胞+G-CSF治疗组(MC组)。上述各组再随机分为6、24小时组,各治疗组分别给予地塞米松注射液、干细胞或干细胞+G-CSF进行治疗,于造模或剖腹探查术后6、24小时后分别采取血清、腹腔积液和肝、肺、胰和肾脏组织标本,记录大鼠的病死率,检测血清中肝、肾功能指标和淀粉酶的含量,测定腹腔积液量/体重比值,观察大鼠多脏器病理改变,并进行病理评分。结果 (1)6和24小时各组大鼠存活率的比较:SO组24小时点存活率明显大于SAP组和各个治疗组(P均<0.05);D组24小时点存活率明显大于SAP组(P<0.05),其余组无明显差异(P>0.05)。(2)各组6小时点多项指标检测结果的比较:D组胰腺评分、腹腔积液与体重比值、肝肾功能指标、淀粉酶含量明显大于SO组(P<0.05或P<0.01)。(3)24小时点D组大鼠的胰腺病理评分明显大于SO组(P<0.05)。(4)M组及MC组大鼠的胰腺组织内均可见荧光染料清晰显影。结论地塞米松能明显降低SAP大鼠病死率,疗效优于M组及MC组。M组和MC组大鼠的存活率、胰腺病理评分,腹腔积液与体重比值和肝肾功能指标,淀粉酶含量与SAP组比较,均无明显差别。MSC收集和培养过程复杂,需要较长的时间才能产生出治疗效果,而采用MSC治疗SAP需要一定的起效时间,假如冒然用于急、重症疾病的治疗缺乏现实意义和足够的理论支持。因此,我们认为MSC难以成为治疗SAP的新手段。

Objective To study the effects of MSC on SAP rats and discuss reasons of the failure. Methods We divided rats into 5 groups： sham operation group （SO group）, group with severe acute pancreatitis （SAP group）, dexamethasone treated group （D group）, Mesenchymal stem cells treated group （M group） and mesenchymal stem cells ＋ G- CSF treated group （MC group）. The groups above were again divided into 6 - hour and 24 - hour groups according to the molding or laparotomy time. All the treated groups were given dexamethasone injection, stem cells or stem cells ＋ G - CSF, respectively. The mortality rate was recorded. The changes of indexes of liver function and renal function as well as content of amylase in blood serum were detected. Ascites volume/weight ratio was de- termined and pathological changes and pathological scores of multiple organs were observed and recorded at 6 and 24 hours after operation. Results （ 1 ） Comparison of 6 - hour and 24 - hour survival rate of all groups ： 24 - hour survival rate of SO group was significantly higher than that in SAP group and all treated groups （ P 〈 0.05 ） ; the survival rate at 24 - hour in D group was significantly higher than that of SAP group （ P 〈 0.05 ）, but there was no significant difference among other groups （ P 〉 0.05 ）. （2） Comparision of the detection results of all groups at 6 - hour point ： the pathological score of pancreas, ascites volume/weight ratio, indexes of liver and renal function and con- tent of amylase in D group and SAP group at 6 - hour were significantly higher than those of SO group （ P 〈 0.05 or P 〈 0.01 ）. （3） The pathological score of pancreas in D group at 24 - hour was significantly higher than that of SO group （ P 〈 0.05 ）. （ g ） The fluorescence dye for staining pancreas tissues was seen clearly in M group and MC group. Conclusion Dexamethasone can significantly decrease the mortality of SAP rats, its curative effect is better than that of. M group and MC group. Considering the survival rate, pathological score of pancreas, ascites volume/weight ratio, indexes of liver and renal function as well as content of amylase of rats in M group and MC group have no significant benefit compared to those of SAP group. The MSC collection and training process is complicated. It need take a long time to produce the effect of treatment. To treat SAP with MSC requires the onset time. If we adventure to treat acute or severe diseases with MSC, this method is lack of realistic and sufficient theoretical support. We guess that MSC is less likely to be developed into a newstrategy to treat SAP.