Cai Jianping, Zhou Xianghong, Yu Haibo, Xue Huanzhou, Li Deyu
Department of Hepatobiliary and Pancreatic Surgery, Henan Province People's Hospital Zhengzhou 450000, Henan, China.
Department of Cardiology, Fuwei Central China Cardiovascular Disease Hospital Zhengzhou 450000, Henan, China.
Am J Transl Res. 2019 Aug 15;11(8):4809-4816. eCollection 2019.
The effect of bone marrow mesenchymal stem cells (BMSCs) on RhoA/ROCK signal pathway expression in severe acute pancreatitis (SAP) was investigate in the present study. SAP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. SD rats were then randomly divided into four groups: normal control, untreated SAP, BMSCs transplant + SAP and ROCK inhibitor + SAP groups (N = 30 each). All rats were sacrificed at 6, 12 and 24 h followed by analysis of serum amylase, TNF-α and IL-6 levels by ELISA, RhoA and ROCK I expression in pancreatic tissues by Western blot, morphological change by HE staining. CM-Dil labelled BMSC can be observed in transplant group. Compared to control group, untreated SAP group had significantly elevated serum amylase, ascites, and levels of TNF-α and IL-6 (P<0.05) in a time-dependent manner, with enhanced pancreatic RhoA and ROCK I protein expression (P<0.05). However, BMSCs transplant group showed decreased serum amylase, ascites, TNF-α and IL-6, plus lower RhoA or ROCK I protein expression (P<0.05). Meanwhile, Y-27632 intervention group also showed lower serum amylase or ascites, plus lower RhoA or ROCK I (P<0.05). HE staining showed improved pathological score in BMSCs transplant or Y-27632 intervention group (only at 6 h time point) compared to untreated SAP group (P<0.05). Pancreatic expression of RhoA and ROCK I is up-regulated in SAP, with severe pancreatic tissue damage. BMSCs can alleviate pancreatic injury possibly through decreasing serum inflammatory factor level and inhibiting RhoA/ROCK signal pathway.
本研究旨在探讨骨髓间充质干细胞(BMSCs)对重症急性胰腺炎(SAP)中RhoA/ROCK信号通路表达的影响。通过将5%牛磺胆酸钠逆行注射入胆胰管建立SAP模型。然后将SD大鼠随机分为四组:正常对照组、未治疗的SAP组、BMSCs移植+SAP组和ROCK抑制剂+SAP组(每组N = 30)。在6、12和24小时处死所有大鼠,通过ELISA分析血清淀粉酶、TNF-α和IL-6水平,通过蛋白质印迹法分析胰腺组织中RhoA和ROCK I的表达,通过HE染色观察形态学变化。在移植组中可观察到CM-Dil标记的BMSC。与对照组相比,未治疗的SAP组血清淀粉酶、腹水以及TNF-α和IL-6水平显著升高(P<0.05),且呈时间依赖性,胰腺RhoA和ROCK I蛋白表达增强(P<0.05)。然而,BMSCs移植组血清淀粉酶、腹水、TNF-α和IL-6降低,RhoA或ROCK I蛋白表达也降低(P<0.05)。同时,Y-27632干预组血清淀粉酶或腹水也降低,RhoA或ROCK I也降低(P<0.05)。HE染色显示,与未治疗的SAP组相比,BMSCs移植组或Y-27632干预组(仅在6小时时间点)病理评分改善(P<0.05)。SAP中RhoA和ROCK I的胰腺表达上调,伴有严重的胰腺组织损伤。BMSCs可能通过降低血清炎症因子水平和抑制RhoA/ROCK信号通路来减轻胰腺损伤。