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丹参酮ⅡA磺酸钠对重症急性胰腺炎大鼠血管内皮的保护作用

Endothelial Protection of Tanshinone in Rats of Severe Acute Panreatitis

  • 摘要: 目的 探讨丹参酮ⅡA磺酸钠对重症急性胰腺炎 (SAP)大鼠内皮细胞的保护作用以及对主动脉内皮细胞凋亡的影响。方法 采用8%L-精氨酸溶液腹腔注射制作大鼠SAP模型,分为SAP组和丹参酮治疗组。丹参酮治疗组于SAP造模成功后立即腹腔注射丹参酮ⅡA磺酮钠20 mg/kg。各组动物分别于术后12 h和24 h各取12只腹主动脉穿刺取血后处死,HE染色观察胰腺组织病理学变化;取腹主动脉行TUNEL和RT-PCR检测。检测:①采用双抗夹心酶联免疫吸附法 (ELLSA)定量测定血清血管内皮细胞损伤标志物血管性血友病因子 (vWF)、可溶性血管内皮细胞蛋白C受体 (sEPCR)以及肿瘤坏死因子-α (TNF-α)和一氧化氮(NO)的浓度。②TUNEL法检测主动脉内皮原位凋亡。③采用RT-PCR检测主动脉内皮Bcl-2和Bax基因mRNA表达。结果 SAP组病理改变较丹参酮组严重。与SAP组相比,丹参酮治疗组降低各时点TNF-α和血管内皮损伤标志物vWF、sEPCR的表达、增加NO的表达,并降低主动脉内皮细胞的凋亡以及增加Bcl-2基因mRNA表达、降低Bax基因mRNA表达,同时也增加SAP大鼠主动脉内皮Bcl-2/Bax基因表达的比值 (P均<0.05)。结论 丹参酮ⅡA磺酸钠可以减轻SAP大鼠主动脉内皮损伤及内皮细胞的凋亡,其机制与抑制TNF-α表达的增加有关。

     

    Abstract: 【Abstract】 Objective To investigate the protective effection of tanshinone on endothelial cells of severe acute panreatitis (SAP) rats and the effection of tanshinone on apoptosis of aorta endothelium. Methods Using 8% L-arginine intraperitoneal to inject in rats, 4.4 mg/g per time, repeat injection 1 hour later, for establishing SAP model. Model rats were randomly divided into SAP group and tanshinone group. 20 mg/kg Sodium Tanshinon Ⅱ Asilate i.p. was applied to tanshinone group,while the saline was used to replace Sodium Tanshinon Ⅱ Asilate in SAP group. Twelve rats of each group were sacrificed at 12 h, 24 h after treatment. The pathological changes in pancreatic tissues were observed.Abdominal aorta samples were collected for terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labelling (TUNEL) and reverse transcription PCR (RT-PCR) tests. The blood samples were collected from abdominal aorta for analysis. Detections: ① The concentration of Von Willebrand factor (vWF), soluble endothelial protein C receptor (sEPCR), tumor necrosis factor alpha (TNF-α) and the serum levels of nitric oxide (NO) were quantitative messured by ELISA. ②The apoptosis of aorta endothelium cell was examined using TUNEL method. ③ Bcl-2 and Bax mRNA expression were measured by RT-PCR. Results The pathological changes of pancreatic tissues were more severe in SAP group than those in tanshinone group. Compared with SAP group, treatment with tanshinone effectively inhibited TNF-α (P<0.05), vWF (P<0.05)and sEPCR (PBcl-2 mRNA (P<0.05), Bcl-2 mRNA/Bax mRNA ratio (P<0.05) and the expression of BaxmRNA (P<0.05) were decreased significantly. Conclusion Sodium Tanshinon ⅡAsilate can lighten the SAP rats aortic endothelial injury and apoptosis of endothelial cells can reduce endothelial damage of SAP rats by TNF-α expression suppression.

     

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