人脂肪间充质干细胞对急性坏死性胰腺炎大鼠治疗疗效的观察  

Experimental observation of human adipose mesenchymal stem cells transplantation in the treatment of acute necrotic pancreatitis in rats

作　　者：庄培涛 谭雪莹[1] 邱建涛[2] 葛倩[1] 邢雪[1] 类成刚[1] 

机构地区：[1]青岛大学医学部附属青岛市市立医院肝胆胰外科,山东青岛266071 [2]青岛大学附属医院心血管外科

出　　处：《中华胰腺病杂志》2017年第2期82-87,共6页Chinese Journal of Pancreatology

基　　金：青岛市科委课题[12-14-16-（5）-jch]

摘　　要：目的 观察人脂肪间充质干细胞（hADMSCs）对急性坏死性胰腺炎（ANP）大鼠胰腺组织修复及炎症反应的影响,探讨其可能机制.方法 分离、纯化hADMSCs,流式细胞仪检测hADMSCs表面标志物CD90、CD29、CD34、CD45.将80只体重170-210 g SD雄性大鼠按完全随机法分为4组,对照组8只,其余每组24只.对照组不做任何处理;假手术组行开腹翻动肠壁后关腹;ANP组采用开腹后牛磺胆酸钠胆胰管逆行注射法制模;hADMSCs组在制模后12 h将DAPI标记的hADMSCs通过尾静脉注射入大鼠体内.观察各组12、24、48 h大鼠的存活情况、胰腺的大体形态及病理变化,检测血清淀粉酶活性及TNF-α、IL-6、IL-10水平;观察hADMSCs在大鼠胰腺、肝脏、肺组织中的分布情况.结果 对照组与假手术组大鼠全部存活,ANP组大鼠术后24、48 h分别死亡5、11只.hADMSCs组术后48 h死亡12只,与ANP组比较,差异无统计学意义（P〉0.05）.hADMSCs组术后胰腺病理损伤程度较ANP组减轻.hADMSCs组术后12、24、48 h的淀粉酶活性分别为（999±110）、（1831±110）、（3991±130）U/L,TNF-α水平为（62.40±2.35）、（80.51±4.51）、（93.46±6.60）ng/L,IL-6水平为（60.46±7.34）、（80.61±8.40）、（100.58±9.49）ng/L,较ANP组的（2 402±146）、（3 292±137）、（5 632±112）U/L,（87.13±3.39）、（105.41±10.06）、（114.57±3.06）ng/L,（70.67±10.90）、（107.61±10.53）、（145.34±10.48）ng/L均显著降低,差异具有统计学意义（P值均〈0.05）;IL-10水平为（56.63±6.35）、（80.38±5.71）、（100.26±6.51）ng/L,较ANP组（45.26±8.04）、（68.25±8.42）、（81.32±5.96）ng/L均显著升高,差异具有统计学意义（P值均〈0.05）.hADMSCs可迁移到胰腺、肝脏、肺脏等受损组织内,以胰腺组织内数量最多,肺组织次之,肝脏组织最少.结论 hADMSCs参与胰腺组织损伤的修复,其机制可能与抑制TNF-α、IL-6分泌,增加IL-10分泌,从而减轻炎症反应有关.Objective To observe the effect of human adipose mesenchymal stem cells （hADMSCs） on pancreatic tissue repair and inflammatory reaction of acute necrotic pancreatitis （ANP） in rat, and explore the possible mechanism.Methods Isolation and purification of hADMSCs and flow cytometry to detect the the surface markers including CD90, CD29, CD34 and CD45 were performed.Eighty SD male rats with the body weight of 170-210 g were randomly divided into 4 groups.There were 8 rats in the control group, 24 rats in other group.Control group underwent no treatment;sham operation group underwent intestinal wall stirring and then abdominal closure;ANP model group was established by open abdominal retrograde injection of sodium taurocholate into bile duct;and in hADMSCs group, DAPI labeled hADMSCs were injected by tail vein into the rat at 12 h after sodium taurocholate injection.The survival of the rats, and gross morphological and pathological changes of the pancreas was observed at 12, 24, and 48 h, and the serum TNF-α, IL-6, IL-10 and amylase were detected.The distribution of hADMSCs in the pancreas, liver and lung was examined in hADMSCs group.Results Rats in control group and sham operation group were all alive.In ANP group, 5 and 11 rats were dead at 24 and 48 h, respectively, and in hADMSCs group 12 rats were dead at 48 h.Compared with ANP group, the difference was not statistically significant （P〉0.05）.The pathological changes of the pancreas were significantly less severe in hADMSCs group than in ANP group.In hADMSCs group, the amylase at 12, 24 and 48 h was（999±110 ）、（1 831±110）、（3 991±130 ）U/L;TNF-α level was （62.40±2.35）, （80.51±4.51） and （93.46±6.60）ng /L;IL-6 was （60.46±7.34）, （80.61±8.40） and（100.58±9.49）ng /L;and these were all significantly lower than those in ANP model group [amylase （2 402±146）, （3 292±137） and （5 632±112）U/L;TNF-α（87.13±3.39）, （105.41±10.06）, （114.57±3.06）ng/L;IL-6 （70.67±10.90）、（107.61±10

关 键 词：胰腺炎 急性坏死性 间质干细胞 干细胞移植 大鼠 

分 类 号：R576[医药卫生—消化系统]