骨髓间充质干细胞对急性胰腺炎大鼠p38丝裂原活化蛋白激酶信号通路表达的影响  

Effect of bone mesenchymal stem cells on p38 mitogen-activated protein kinase expression in pancreas of rats with acute pancreatitis

作　　者：杨平[1] 宋振顺[2] 寇明文[1] 卢鹏[1] 赵戈[1] 张福琴[1] 

机构地区：[1]第四军医大学西京医院肝胆胰脾外科,西安710032 [2]同济大学附属第十人民医院肝胆胰外科

出　　处：《中华实验外科杂志》2012年第7期1339-1341,F0004,共4页Chinese Journal of Experimental Surgery

摘　　要：目的观察骨髓间充质干细胞（MSCs）对急性胰腺炎（AP）大鼠p38丝裂原活化蛋白激酶（p38MAPK）信号通路的影响，探讨其减轻胰腺炎的作用机制。方法采用腹腔注射L-精氨酸建立大鼠AP模型。SD大鼠随机分4组：AP未治疗组（24只）；MSCs移植组（24只）；p38MAPK抑制组（24只）和正常对照组（6只）。流式细胞术检测MSCs表面标记物；逆转录-聚合酶链反应（RT—PCR）方法检测胰腺组织p38MAPKmRNA表达变化；同时观察组织形态学改变。结果（1）未治疗组大鼠在建模后1h时胰腺组织p38MAPKmRNA表达显著升高并达到顶峰（P〈0．01）；移植MSCs后表达明显降低，与正常对照组比较，差异无统计学意义（P〉0．05）。（2）未治疗组血清炎性因子水平分别为：肿瘤坏死因子（TNF）-α（614．8±54．6）ng／L、白细胞介素（IL）-1（3040．5±506．4）ng／L、IL-17（4．5±0．4）U／L，胰腺组织中性粒细胞趋化因子（CINC）和单核粒细胞趋化因子（MCP-1）染色阳性率均明显升高（P〈0．05）；移植MSCs后，CINC、MCP-1染色阳性率显著下降，血清炎性因子水平分别为：TNF-α（277．5±60．8）ng／L、IL-1（1056．2±563．1）ng／L、IL-17（1．2±0．4）U／L，两组比较差异有统计学意义（P〈0．05）。（3）胰腺组织苏木素-伊红（HE）染色显示，未治疗组有大量炎性细胞浸润，胰腺细胞破坏明显，腺体结构紊乱，而移植组仅见少量炎性细胞浸润，细胞偶有破坏，排列整齐，结构有序。结论急性胰腺炎时，胰腺组织内p38MAPKmRNA表达上调，胰腺组织损伤严重。MSCs移植可以明显抑制p38MAPKmRNA表达，降低胰腺组织内趋化因子和血清炎性因子水平，从而减轻胰腺损伤。Objective To investigate the effect of bone mesenchymal stem cells （MSCs） on p38 mitogen-aetivated protein kinase （p38MAPK） expression in pancreas of rats with acute pancreatitis （AP）, and the conceivable mechanism was then deduced. Methods AP was induced in SD rats by 2 intraperito- heal injection of 20% L-arginine hydrochloride three times at a 1-h interval. Rats were randomly divided into AP untreated group （ n = 24）, MSCs transplanted group （ n = 24）, p38MAPK inhibited group （ n = 24） and control group （n =6）. MSCs with surface markers were measured by flow cytometry, p38MAPK mRNA expression in the pancreas was detected by reverse transeription-polymerase chain reaction （ RT- PCR） , and histological changs of the pancreas were observed. Results p38MAPK mRNA could be de- tected in the pancreas with low values in control group, markedly increased and peaked in 1 h in AP un- treated group （P 〈 0. 01 ）. Transplantation of MSCs could effectively inhibit p38MAPK mRNA expression. The serum inflammatory factors were highly expressed [ tumor necrosis factor （TNF）-α（614. 8 ± 54. 6） ng/L, interleukin （IL） -1 （ 3040. 5 ± 506.4） ng/L, IL-17 （4. 5 ± 0.4） U/L] , and pancreatic ehemotae- tie factors （ MCP-1, CINC） were markedly increased （P 〈 0. 05 ） in AP untreated group. After MSCs transplantation, the levels of serum inflammatory factors were reduced [ TNF-α （ 277.5 ± 60. 8 ） ng/L, IL- l （ 1.56. 2 ±563. 1 ） ng/L, IL-17 （ 1.2 ±0. 4） U/L] , and pancreatic chemotactie factors were decreased （ P 〈 0. 05 ）. Conclusion The expression of p38 MAPK mRNA is increased in the pancreas of AP and the pancreas injuries are aggravated. MSCs could markedly inhibit p38MAPK mRNA expression in the pancre- as of AP, which would lead to relief of pancreas injury.

关 键 词：P38丝裂原活化蛋白激酶 骨髓间充质干细胞 急性胰腺炎 移植 

分 类 号：R657.51[医药卫生—外科学]