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蛇床子素对小鼠肠缺血再灌注损伤的影响及机制

[Effects and mechanism of osthole on intestinal ischemia-reperfusion injury in mice].

作者信息

Zhang Zhen, Li Fan-fan, Lu Ming-dian, Li Yong-xiang

机构信息

Department of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.

Department of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China. Email:

出版信息

Zhonghua Yi Xue Za Zhi. 2013 Sep 24;93(36):2913-6.

Abstract

OBJECTIVE

To explore the protective role of osthole in intestinal ischemia-reperfusion (I/R) injury in mice and examine its underlying mechanism.

METHODS

A murine model of intestinal I/R injury was established with clamping of superior mesenteric artery for 120 min and then clamping was relieved for 60 min. Forty-five SD male mice weighing 27-31 g were randomly divided into 3 groups (n = 15 each): sham group (S), I/R injury group (I/R) and I/R plus osthole treatment group (Ost+). Intestinal wet/dry weight ratio, superoxide dismutase (SOD), malondialdehyde (MDA) in serum were examined by colorimetric assay and diamine oxidase (DAO) was examined by automatic biochemical analyzer, the levels of tumor necrosis factor (TNF) -α, interleukin (IL)-1β and IL-2 were examined by enzyme-linked immunosorbent assay (ELISA). Intestinal barrier permeability was detected by Evans blue (EB) test. One-way ANOVA was used to analyze all experimental data variance.

RESULTS

Intestinal tissues wet/dry weight ratios, Evans blue content and Chiu's score of I/R group mice were significantly higher than those of S and Ost+ groups (0.80% ± 0.03% vs 0.77% ± 0.02% & 0.78% ± 0.02%, (0.11 ± 0.04) vs (0.05 ± 0.02) & (0.06 ± 0.02) µg/mg, 3.42 ± 0.73 vs 0.87 ± 0.35 & 2.63 ± 0.58, P < 0.05 or P < 0.01) . Serum level of DAO, MDA, IL-1β & TNF-α of I/R group mice were significantly higher than those of S and Ost+ groups ( (18.9 ± 4.0) vs (14.5 ± 2.3) & (16.0 ± 2.6) U/L, (8.4 ± 1.2) vs (6.9 ± 1.7) & (6.1 ± 2.4) µmol/L, (93 ± 6) vs (51 ± 4) & (67 ± 5) ng/L, (467 ± 31) vs (235 ± 21) & (323 ± 30) ng/L, P < 0.01 or P < 0.05) . Serum SOD activity and IL-2 level were significantly lower than those of S and Ost+ groups ( (75 ± 7) vs (93 ± 16) & (89 ± 5) U/ml, (95 ± 16) vs (198 ± 14) & (139 ± 11) ng/L, all P < 0.05) . All parameters showed no significant difference between S and Ost+ groups (all P > 0.05).

CONCLUSIONS

Treatment of osthole may protect murine intestinal tissue against intestinal I/R injury. And the mechanisms may be due to its actions of preventing oxygen stress and inflammatory responses.

摘要

目的

探讨蛇床子素对小鼠肠缺血再灌注(I/R)损伤的保护作用,并探究其潜在机制。

方法

建立小鼠肠I/R损伤模型,夹闭肠系膜上动脉120分钟,然后松开夹闭60分钟。将45只体重27 - 31克的SD雄性小鼠随机分为3组(每组n = 15):假手术组(S)、I/R损伤组(I/R)和I/R加蛇床子素治疗组(Ost+)。采用比色法检测肠湿/干重比、血清中超氧化物歧化酶(SOD)、丙二醛(MDA)含量,用自动生化分析仪检测二胺氧化酶(DAO),采用酶联免疫吸附测定法(ELISA)检测肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-2水平。通过伊文思蓝(EB)试验检测肠屏障通透性。采用单因素方差分析对所有实验数据的差异进行分析。

结果

I/R组小鼠的肠组织湿/干重比、伊文思蓝含量和Chiu评分显著高于S组和Ost+组(0.80% ± 0.03% 对0.77% ± 0.02%和0.78% ± 0.02%,(0.11 ± 0.04)对(0.05 ± 0.02)和(0.06 ± 0.02)μg/mg,3.42 ± 0.73对0.87 ± 0.35和2.63 ± 0.58,P < 0.05或P < 0.01)。I/R组小鼠血清DAO、MDA、IL-1β和TNF-α水平显著高于S组和Ost+组((18.9 ± 4.0)对(14.5 ± 2.3)和(16.0 ± 2.6)U/L,(8.4 ± 1.2)对(6.9 ± 1.7)和(6.1 ± 2.4)μmol/L,(93 ± 6)对(51 ± 4)和(67 ± 5)ng/L,(467 ± 31)对(235 ± 21)和(323 ± 30)ng/L,P < 0.01或P < 0.05)。血清SOD活性和IL-2水平显著低于S组和Ost+组((75 ± 7)对(93 ± 16)和(89 ± 5)U/ml,(95 ± 16)对(198 ± 14)和(139 ± 11)ng/L,均P < 0.05)。S组和Ost+组之间所有参数均无显著差异(均P > 0.05)。

结论

蛇床子素治疗可保护小鼠肠组织免受肠I/R损伤。其机制可能是由于其具有预防氧化应激和炎症反应的作用。

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