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姜黄素对实验性急性胰腺炎早晚期促炎细胞因子和组织损伤的影响。

Effects of curcumin on proinflammatory cytokines and tissue injury in the early and late phases of experimental acute pancreatitis.

机构信息

Department of Pathology, Faculty of Veterinary Medicine, Istanbul University, 34320 Avcilar, Istanbul, Turkey.

出版信息

Pancreatology. 2013 Jul-Aug;13(4):347-54. doi: 10.1016/j.pan.2013.05.005. Epub 2013 May 21.

Abstract

BACKGROUND & AIMS: Acute pancreatitis (AP) varies from mild to severe necrotizing changes with high mortality. The objective of the current study was to investigate the effects of curcumin on tissue injury and proinflammatory cytokines in the early and late phases of AP.

METHODS

AP was induced by sodium taurocholate in rats (n = 140). First group was left untreated. Group II received 100 mg/kg curcumin daily starting 20 days before AP induction. The rats were allocated into 7 sub-groups (n:5) and were sacrificed at 2, 6, 12, 24, 72, 144 and 288 h following the induction of AP. Blood and pancreatic tissue samples were collected for biochemical and histopathologic evaluations and the assessment of protein and mRNA levels, as well.

RESULTS

Curcumin decreased total histopathologic scores in comparison with those of the taurocholate group (P < 0.05). Curcumin increased Caspase-3 activity and decreased trypsin activity, while inhibited nuclear factor-κ (NF-κB) at all time points (P < 0.05) and moreover reduced activator protein-1 (AP-1). Curcumin decreased chemokine (except for 288 h), TNF-α (except for 2 and 24 h), IL-6 (except for 2, 6 and 288 h) and iNOS (except for 144 and 288 h) mRNA levels (P < 0.05). Curcumin serum nitric oxide (NO) (except for 144 and 288 h) levels were reduced, as well.

CONCLUSIONS

In conclusion, curcumin reduced tissue injury, trypsin activation and inhibited NF-κB and AP-1. However TNF-α, IL-6 and iNOS and NO were not inhibited at all time points. Therefore no direct correlation was detected in the subgroups between tissue injury, proinflammatory cytokines and oxidative enzymes.

摘要

背景与目的

急性胰腺炎(AP)从轻度到严重坏死性变化不等,死亡率高。本研究的目的是探讨姜黄素对 AP 早期和晚期组织损伤和促炎细胞因子的影响。

方法

用牛磺胆酸钠诱导大鼠 AP(n = 140)。第一组未治疗。第二组在 AP 诱导前 20 天开始每天给予 100mg/kg 姜黄素。将大鼠分为 7 个亚组(n:5),在 AP 诱导后 2、6、12、24、72、144 和 288 小时处死。收集血液和胰腺组织样本进行生化和组织病理学评估,并评估蛋白质和 mRNA 水平。

结果

与牛磺胆酸钠组相比,姜黄素降低了总组织病理学评分(P < 0.05)。姜黄素增加了 Caspase-3 活性,降低了胰蛋白酶活性,同时在所有时间点抑制了核因子-κ(NF-κB)(P < 0.05),并减少了激活蛋白-1(AP-1)。姜黄素降低了趋化因子(288 小时除外)、TNF-α(2 和 24 小时除外)、IL-6(2、6 和 288 小时除外)和 iNOS(144 和 288 小时除外)mRNA 水平(P < 0.05)。姜黄素血清一氧化氮(NO)(144 和 288 小时除外)水平也降低。

结论

总之,姜黄素减轻了组织损伤、胰蛋白酶激活,并抑制了 NF-κB 和 AP-1。然而,TNF-α、IL-6 和 iNOS 和 NO 并非在所有时间点都受到抑制。因此,在亚组中未发现组织损伤、促炎细胞因子和氧化酶之间存在直接相关性。

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