骨髓间充质干细胞移植对慢性胰腺炎大鼠模型胰腺纤维化的影响

The effects of bone marrow mesenchymal stem cell transplantation on pancreatic fibrosis in rats with chronic pancreatitis

目的观察骨髓间充质干细胞(BMSCs)移植对慢性胰腺炎大鼠模型胰腺纤维化的影响,并探讨其作用机制。方法将30只健康雄性SD大鼠随机分为对照组、模型组和移植组,每组10只。模型组采用胆胰管逆行注射油酸法制备大鼠慢性胰腺炎模型,对照组以同样方式仅注射相同体积生理盐水,移植组在造模后1周和5周经尾静脉注射BMSCs。分别于造模后第1、4和8周称量3组大鼠体质量,于第8周后剖杀动物,取胰腺组织行HE染色和饱和苦味酸-天狼猩红染色观察胰腺组织病理学改变并评分,采用ELISA法检测胰腺组织转化生长因子(TGF)-β1、Ⅰ型胶原和Ⅲ型胶原含量。结果造模后第4周,模型组和移植组大鼠体质量均低于对照组(P<0.05),模型组与移植组间差异无统计学意义(P>0.05);至第8周,模型组和移植组大鼠体质量仍低于对照组,而移植组高于模型组(P<0.05)。模型组大鼠胰腺组织纤维化评分升高、TGF-β1、Ⅰ型胶原和Ⅲ型胶原含量均高于对照组和移植组(P<0.05);移植组胰腺组织纤维化评分高于对照组,TGF-β1、Ⅰ型胶原和Ⅲ型胶原含量与对照组差异无统计学意义。结论BMSCs移植能减少慢性胰腺炎大鼠胶原分泌,降低胰腺纤维化程度,其机制可能与抑制TGF-β1分泌有关。

Objective To investigate the effects and mechanisms of bone marrow mesenchymal stem cells （BMSCs） on pancreatic fibrosis in rats of chronic pancreatitis. Methods Thirty healthy male SD rats were randomly divided into three groups：control group, model group and transplanted group （n=10 for each group）. Chronic pancratitis rat model was induced by retrograde injection of oleic acid into the biliopancreatic duct. The sham operation group was treated only with solvent. Transplanted group was given BMSCs through caudal vein injection at 1 week and 5 weeks after the model induction. All rats were weighed at 1 week, 4 weeks and 8 weeks in three groups. After 8-week feeding,pancreatic tissues were harvested for HE and picric-sirius staining. The contents of transforming growth factorβ1 （TGF-β1）, typeⅠcollagen and typeⅢcollagen were detcted by using ELISA. Results Compared with the control group, the weights of rats were decreased at 4 weeks and 8 weeks in model group and transplantated group （P〈0.05）. There were no significant differences in body weights between model group and transplantated group （P〉0.05）. The pancreatic fibrosis score and pathological injury were ameliorated signicantly in transplanted group. The contents of TGF-β1, typeⅠcollagen and typeⅢcollagen in pancreas were increased in model group than those of control group and transplanted group （P〈0.05）. Conclusion BMSCs transplantation can reduce the collagen secretion and reduce the degree of pancreatic fibrosis in rats with chronic pancreatitis, which may be related to the inhibition of the release of TGF-β1.