依达拉奉对大鼠急性坏死性胰腺炎的保护作用

目的:探讨自由基清除剂依达拉奉对大鼠急性坏死性胰腺炎的保护作用及其机制.方法:90只♂SD大鼠随机分为假手术组(SHAM组)、坏死性胰腺炎组(ANP组)、依达拉奉治疗组(EDA组),每组30只.SHAM组为开腹后只翻动十二指肠及胰腺后关腹;ANP组胰胆管内逆行输注1.5%脱氧胆酸钠制备急性坏死性胰腺炎模型;EDA组为ANP造模后立即尾静脉注射依达拉奉(6mg/kg).分别于术后6、12、24h处死大鼠(每个时点10只),观察胰腺病理形态改变并评分;检测血清淀粉酶、TNF-α、ET-1、sICAM-1含量;检测胰腺组织中丙二醛(MDA)含量及总超氧化物歧化酶(T-SOD)活力.结果:与ANP组比较,EDA治疗组在胰腺病理改变、血清TNF-α水平(6h:109.6ng/L±49.0ng/Lvs190.2ng/L±46.6ng/L,12h:405.4ng/L±116.3ng/Lvs559.7ng/L±203.9ng/L,24h:415.4ng/L±164.6ng/Lvs648.7ng/L±222.1ng/L,均P<0.05)、血清ET-1水平(6h:45.6ng/L±13.5ng/Lvs66.0ng/L±16.0ng/L,12h:83.5ng/L±15.4ng/Lvs96.8ng/L±23.0ng/L,24h:85.1ng/L±25.8ng/Lvs103.9ng/L±28.9ng/L),血清sICAM-1水平(6h:0.58ng/L±0.13ng/Lvs0.78ng/L±0.14ng/L,12h:0.78ng/L±0.10ng/Lvs0.94ng/L±0.12ng/L,24h:0.96ng/L±0.16ng/Lvs1.24ng/L±0.30ng/L,均P<0.05)、胰腺组织MDA含量(6h:4.22nmol/mgprot±0.40nmol/mgprotvs8.79nmol/mgprot±0.80nmol/mgprot,12h:5.90nmol/mgprot±0.51nmol/mgprotvs12.30nmol/mgprot±1.02nmol/mgprot,24h:9.10nmol/mgprot±0.84nmol/mgprotvs17.88nmol/mgprot±1.43nmol/mgprot)均有不同程度减轻(均P<0.05),T-SOD活力增强(6h:88.6U/mgprot±7.1U/mgprotvs68.8U/mgprot±10.5U/mgprot,12h:77.6U/mgprot±6.8U/mgprotvs46.0U/mgprot±8.9U/mgprot,24h:45.5U/mgprot±5.3U/mgprotvs27.8U/mgprot±4.3U/mgprot,均P<0.05);血清淀粉酶变化无显著差异.与SHAM组比较,ANP组胰腺组织病理评分、血清淀粉酶、TNF-α、ET-1、sICAM-1明显升高,胰腺组织MDA含量升高,T-SOD活力下降,差异均有统计学意义.结论:依达拉奉可以清除坏死性胰腺炎体内过量生成的氧自由基并减少炎性因子的表达,减轻胰腺组织损伤.

Protective effects of edaravone against acute necrotizing pancreatitis in rats

AIM: To investigate whether edaravone has protective effects against acute necrotizing pancreatitis (ANP) in rats and to explore the possible mechanisms involved. METHODS: Ninety male Spraque-Dawley rats were randomly and equally divided into sham operation group, ANP group and edaravone treatment group (EDA group). ANP was induced in rats of the ANP and EDA groups by retrograde injection of 1.5% deoxycholate. The EDA group was injected with edaravone (6 mg/kg) via the tail vein immediately after ANP induction. The rats were sacrificed 6, 12, and 24 h after the operation. Pathological changesin the pancreas were observed and graded. Serum levels of amylase, tumor necrosis factoralpha (TNF-?), endothelin-1 (ET-1) and soluble intercellular adhesion molecule-1 (sICAM-1), as well as malonic dialdehyde (MDA) content and superoxide dismutase (T-SOD) activity in pancreatic tissue were measured. RESULTS: Compared to the sham operation group, pancreatic pathological scores, serum levels of amylase, TNF-?, ET-1 and sICAM-1, and the contents of MDA in pancreatic tissue were significantly increased, and T-SOD activity in pancreatic tissue was significantly decreased in the ANP group. Compared to the ANP group, pancreatic pathological scores, serum levels of TNF-? (6 h: 109.6 ng/L ± 49.0 ng/L vs 190.2 ng/L ± 46.6 ng/L, 12 h: 405.4 ng/L ± 116.3 ng/L vs 559.7 ng/L ± 203.9 ng/L, 24 h: 415.4 ng/L ± 164.6 ng/L vs 648.7 ng/L ± 222.1 ng/L, all P < 0.05), ET-1 (6 h: 45.6 ng/L ± 13.5 ng/L vs 66.0 ng/L ± 16.0 ng/L, 12 h: 83.5 ng/L ± 15.4 ng/L vs 96.8 ng/L ± 23.0 ng/L, 24 h: 85.1 ng/L ± 25.8 ng/L vs 103.9 ng/L ± 28.9 ng/L, all P < 0.05), and sICAM-1 (6 h: 0.58 ng/L ± 0.13 ng/L vs 0.78 ng/L ± 0.14 ng/L, 12 h: 0.78 ng/L ± 0.10 ng/L vs 0.94 ng/L ± 0.12 ng/L, 24 h: 0.96 ng/L ± 0.16 ng/L vs 1.24 ng/L ± 0.30 ng/L, all P < 0.05), and the contents of MDA in pancreatic tissue (6 h: 4.22 nmol/mg prot ± 0.40 nmol/mg prot vs 8.79 nmol/mg prot ± 0.80 nmol/mg prot, 12 h: 5.90 nmol/mg prot ± 0.51 nmol/mg prot vs 12.30 nmol/mg prot ± 1.02 nmol/mg prot, 24 h: 9.10 nmol/mg prot ± 0.84 nmol/mg prot vs 17.88 nmol/mg prot ± 1.43 nmol/mg prot, all P < 0.05) were reduced, and T-SOD activity was increased (6 h: 88.6 U/mg prot ± 7.1 U/mg prot vs 68.8 U/ mg prot ± 10.5 U/mg prot, 12 h: 77.6 U/mg prot ± 6.8 U/mg prot vs 46.0 U/mg prot ± 8.9 U/mg prot, 24 h: 45.5 U/mg prot± 5.3 U/mg prot vs 27.8 U/mg prot ± 4.3 U/mg prot, all P < 0.05) in the EDA group. No significant differences were observed in serum levels of amylase between the ANP and EDA groups. CONCLUSION: Edaravone can eliminate the excessive generation of oxygen free radicals, down-regulate the expression of inflammatorycytokines, and reduce tissue injury in rats with ANP.