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[摘要]
目的 观察丹参注射液预防大鼠急性胰腺炎及其对血清肿瘤坏死因子(TNF-α)、白细胞介素(IL-6)、胰腺组织核因子(NF-κB)及氧自由基的影响。方法 将60只SD大鼠随机分为6组, 分别为假手术组、模型组、乌司他丁组(20 000 U/kg)以及丹参注射液低、中、高剂量(0.4、0.8、1.6 mL/kg)组。用5%牛磺胆酸钠(1.0 mL/kg)胰管内注入诱导大鼠急性胰腺炎模型, 造模前30 min分别尾iv给予丹参注射液。各组大鼠均于造模6 h后行腹主动脉采血, 处死大鼠取胰腺组织标本, 检测SD大鼠急性胰腺炎模型血清淀粉酶(AMY)、血浆内毒素(ET)、胰腺病理评分和病死率。并用ELISA法检测血清IL-6、TNF-α浓度的变化, 运用免疫组化法检测NF-κ B表达水平, 同时切取各时间点大鼠胰腺组织, 检测丙二醛(MDA)、组织髓过氧化物酶(MPO)及超氧化物歧化酶(SOD)的水平。结果 模型组大鼠的血清AMY、血浆ET、病理评分、死亡率、IL-6、TNF-α水平及胰腺组织中NF-κB活性、MDA水平和MPO活性均较假手术组升高(P<0.01), 而SOD活性则明显降低(P<0.05);乌司他丁组和丹参注射液组上述各项指标均较模型组明显改善(P<0.05、0.01)。结论 丹参注射液可显著降低实验性急性胰腺炎大鼠的IL-6、TNF-α及NF-κB, 清除氧自由基, 减轻脂质过氧化反应, 从而减轻急性胰腺炎病理损害程度, 降低急性胰腺炎大鼠的死亡率。
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[Abstract]
Objective To investigate prevention of Danshen Injection on rats with acute pancreatitis, and determine the levels of TNF-α, IL-6, nuclear factor-κB (NF-κB) activity and oxygen free radicals. Methods Sixty SD rats were randomly divided into Sham group, model group, ulinastatin (20 000 U/kg) group and low-, mid-, and high-dose Danshen Injection (0.4, 0.8, and 1.6 mL/kg) groups. Acute pancreafitis model was developed by retrograde injection of 5% sodium taurocholate (1.0 mL/kg) into pancreatic duct in rats. Danshen Injection was injected into the tail vein 30 min before sodium taurocholate injection. The abdominal aortic blood and pancreatic specimens were taken 6 h after sodium taurocholate injection for measurement of serum amylase (AMY), plasma endotoxin (ET), pathological scores of pancreas and case-fatality rate. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were determined by ELISA method. Expression of nuclear factor-κB (NF-κB) activity in pancreatic tissue was detected by immunohistochemical method, and oxygen free radicals, such as MDA, MPO, and SOD in each group were observed. Results The levels of serum AMY, plasma ET, pathological score versus, mortality, IL-6, TNF-α concentration, NF-κB levels of pancreas, pancreatic tissue, and the content of MDA and activity of MPO were enhanced (P<0.01), and the activity of SOD was significantly reduced in model group (P<0.05). Danshen Injection groups showed statistical improvement in plasma ET, serum AMY, pathological score, and oxygen free radicals compared with model group (P<0.05, 0.01). Conclusion Danshen Injection can significantly decrease NF-κB activity, IL-6, and TNF-αlevers, scavenge oxygen free radicals, and reduce lipid peroxidation, and therefore alleviate pancreatic damage in pancreas, leading to lowered level of case fatality in rats with acute pancreatitis.
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