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大黄素联合丹参素对实验性重症急性胰腺炎的保护作用。

Protective effects of emodin combined with danshensu on experimental severe acute pancreatitis.

机构信息

Department of Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng St, Nangang Dist 150001, Harbin, Heilongjiang, People's Republic of China.

出版信息

Inflamm Res. 2010 Jun;59(6):479-88. doi: 10.1007/s00011-009-0152-1. Epub 2009 Dec 31.

Abstract

OBJECTIVE AND DESIGN

In the present experiment, we aimed to determine the feasibility and curative effects of emodin combined with danshensu on experimental severe acute pancreatitis (SAP) and the mutual benefit of this synergistic strategy by a prospective animal study.

MATERIAL

Eighty Wistar rats were randomly divided into four groups (n = 20).

TREATMENT

SAP was elicited by a retrograde infusion of 5.0% sodium taurocholate into the pancreatic main duct. SAP rats in each group received no further intervention, emodin alone, danshensu (DSS) alone, and emodin combined with DSS (EDSS), respectively.

METHODS

48 h after SAP induction, all surviving animals were sacrificed to collect blood and tissue samples for the following measurements: serum levels of amylase, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), endotoxin and D-lactate. Pancreatic levels of TNF-alpha, IL-1beta, maleic dialdehyde (MDA), myeloperoxidase (MPO) activity, nuclear factor-kappaappaB (NF-kappaB) activation as well as wet-dry weight ratio were also evaluated. Ascitic fluid was quantified and the severity of pancreatic damage was analyzed by pathological grading and scoring.

RESULTS

Compared with the SAP group, the emodin, DSS and EDSS groups had significant differences in every index. Furthermore, EDSS obviously improved all the parameters mentioned above so as to counteract inflammatory response and oxidative stress, as well as most effectively abating pancreatic and intestinal barrier injury.

CONCLUSIONS

EDSS exerted protective effects on SAP rats and remarkably alleviated the severity of experimental SAP. Mechanisms that might account for the beneficial effects include protecting the intestinal barrier, inhibiting over-inflammatory reaction and abating oxidative stress. The combined strategy proved to be more effective than either emodin or DSS alone and may cause synergistic effects in combination in the early stage of SAP. Broad potential for future clinical practice is foreseeable.

摘要

目的和设计

本实验旨在通过前瞻性动物研究,确定大黄素联合丹参素治疗实验性重症急性胰腺炎(SAP)的可行性和疗效,以及这种协同策略的相互益处。

材料

80 只 Wistar 大鼠随机分为四组(n = 20)。

治疗

通过逆行胰胆管内注入 5.0%牛磺胆酸钠诱发 SAP。每组 SAP 大鼠分别接受不干预、大黄素单独治疗、丹参素(DSS)单独治疗和大黄素联合丹参素(EDSS)治疗。

方法

SAP 诱导后 48 h,处死所有存活动物,收集血液和组织样本,用于以下测量:血清淀粉酶、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、内毒素和 D-乳酸水平。还评估了胰腺组织中 TNF-α、IL-1β、丙二醛(MDA)、髓过氧化物酶(MPO)活性、核因子-κB(NF-κB)激活以及干湿重比。定量腹水并通过病理分级和评分分析胰腺损伤的严重程度。

结果

与 SAP 组相比,大黄素、DSS 和 EDSS 组在所有指标上均有显著差异。此外,EDSS 明显改善了上述所有参数,从而对抗炎症反应和氧化应激,以及最有效地减轻胰腺和肠道屏障损伤。

结论

EDSS 对 SAP 大鼠具有保护作用,并显著减轻实验性 SAP 的严重程度。可能导致有益效果的机制包括保护肠道屏障、抑制过度炎症反应和减轻氧化应激。与单独使用大黄素或 DSS 相比,联合策略证明更有效,并且在 SAP 的早期阶段可能会产生协同作用。未来的临床应用潜力可观。

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