杜仲提取物通过抑制无菌炎症反应发挥对肝缺血再灌注损伤保护作用的研究

Hepatic ischemia reperfusion injury (HIRI) is an important factor affecting the prognosis of liver surgery patients and reducing the success rate of surgery. To find a safety and effective drug to prevent against HIRI is necessary. Eucommia ulmoides is characteristics of Chinese medicinal materials in GuiZhou province, which has more than 2,000 years history of medicinal. It has protective effects to many kinds of liver injury, but few report was seen in HIRI protection. Our preliminary research suggest that eucommia ulmoides extract has a protective effect against HIRI. There still further exploration should be done to identify the mechanisms of the protection effect , whether there are different effects between different Eucommia ulmoides extracting technology. The latest view hold that HIRI is a process of liver injury caused by aseptic inflammation, in which high-mobility group protein B1 (HMGB1) played a key role to initiate and sustain this process. This subject is intended to explore the protective effects of eucommia ulmoides extraction on HIRI and whether HMGB1 was inhibited during aseptic inflammation injury both in vivo and in vitro experiments. It is the first time to explore the protective effect of Eucommia on HIRI for HMGB1 as a initiating point . it is an important complement for traditional Chinese medicine in HIRI protection research. The research can provide theoretical basis for the further development and utilization of eucommia ulmoides.

肝缺血再灌注损伤（HIRI）是影响肝外科手术病人预后及导致手术失败的重要因素，找到安全有效的防治药物迫在眉睫。杜仲为贵州特色中药，有2000年药用史，对多种肝损伤具保护作用，但未见其对HIRI有保护效应的相关报道。我们前期实验结果提示：杜仲提取物可能对HIRI具保护作用，但该效应尚需证实。且不同提取工艺所获杜仲粗提物与单体的保护效应是否具差异性？保护机制如何？需进一步探讨。新观点认为，HIRI是无菌炎症反应所致的肝损伤过程，高迁移率族蛋白B1(HMGB1)在启动和维持此过程发挥关键作用。本课题拟通过体内外实验，明确杜仲提取物对HIRI的保护效应，找到效应最强的提取物，并探讨其是否通过抑制HMGB1释放或表达进而减轻无菌炎症损伤。本课题首次以HMGB1为切入点，探讨杜仲对HIRI保护作用，是对HIRI保护研究的重要补充，对中药抗炎研究也具重要价值。研究结果可为杜仲进一步开发利用提供理论依据。

肝缺血再灌注损伤(HIRI)是影响肝外科手术病人预后及导致手术失败的重要因素，找到安全有效的防治药物迫在眉睫。杜仲为贵州特色中药，有2000年药用史，对多种肝损伤具保护作用，但未见其对HIRI保护效应的相关报道。新近观点认为，HIRI是无菌炎症反应所致的肝损伤过程 ，高迁移率族蛋白B1(HMGB1)在启动和维持此过程发挥关键作用。本项目首先通过不同提取工艺获得杜仲粗提物，再将粗提物与部分杜仲有效成分应用于大鼠HIRI模型，观察其保护效应。并关注HMGB1/TLR-4/NF-κB信号通路对HIRI无菌炎症反应的影响。结果显示，杜仲粗提物、杜仲多糖和绿原酸均可通过抗炎、抗氧化减轻大鼠HIRI，以绿原酸保护效应最强。进一步探讨绿原酸保护机制，发现绿原酸既可通过抑制HMGB1/TLR-4/NF-κB信号通路激活以减轻无菌炎症反应，也可抑制ENDOG和Caspase3等凋亡蛋白表达，上调Bcl-2蛋白表达，以减少肝细胞凋亡进而改善HIRI。但减轻细胞凋亡的具体机制目前尚不明确，需进一步研究阐明。实验还增加了杜仲另外两种有效成分——杜仲多糖和桃叶珊瑚苷对HIRI保护机制的探讨。本项目研究杜仲多种有效成分对HIRI保护作用，是对HIRI药物保护研究的重要补充，对中药抗炎研究也具重要价值。为杜仲进一步开发利用提供了理论依据。