龙血竭通过 PI3K-AKT-mTOR 信号通路对急性心肌梗死模型小鼠发挥心脏保护作用。
Dragon's Blood exerts cardio-protection against myocardial injury through PI3K-AKT-mTOR signaling pathway in acute myocardial infarction mice model.
机构信息
Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
出版信息
J Ethnopharmacol. 2018 Dec 5;227:279-289. doi: 10.1016/j.jep.2018.09.010. Epub 2018 Sep 6.
ETHNOPHARMACOLOGICAL RELEVANCE
Dragon's Blood (DB), the red resin of Dracaena cochinchinensis (Lour.) S. C., has been used in traditional Chinese medicine to treat acute myocardial infarction (AMI) for centuries. Evidence indicated that DB may exert cardio-protective effect by inhibiting inflammatory response during myocardial infarction. However, its pharmaceutical mechanism is still to be elucidated.
AIM OF THE STUDY
Due to its potential anti-inflammatory effect, Dragon's Blood extract (DBE) was applied on AMI mice model in this study and its mechanism on inflammation via PI3K-AKT-mTOR signaling pathway was to be validated.
MATERIALS AND METHODS
AMI mice model was established by ligation of left anterior descending (LAD) arteries. DBE was administered for 7 days before the surgery. Heart function was evaluated by 2D echocardiography. Levels of CK-MB and LDH1 in serum as well as TXB2, 6-keto-PGF1α and ET-1 in plasma were detected. Level of IL-6 in cardiac tissues was quantified by ELISA. Expressions of key proteins in PI3K-AKT-mTOR signaling pathway were detected by Western blot.
RESULTS
The result demonstrated that DBE could improve heart function in AMI mice model. Meanwhile, it could also regulate levels of CK-MB and LDH1, and restore balance between TXB2 and 6-keto-PGF1α. Further study suggested that DBE could inhibit inflammation and regulate expressions of key proteins in IL-6-JAK2/STAT3 pathway in cardiac tissue. Western blot results validated that DBE could activate PI3K-AKT-mTOR signaling pathway, thereby regulating the expressions of its downstream targets, including VEGF, COX2 and PPARγ.
CONCLUSION
DBE exerts cardio-protective efficacy by activating JAK2-STAT3 and PI3K-AKT-mTOR pathways in cardiac tissue. These findings provide insight into the pharmacological mechanism of DBE and validate the beneficial effects of DBE in the clinical application for AMI.
民族药理学相关性
龙血（DB）是龙舌兰科植物龙血树（Dracaena cochinchinensis（Lour.）S. C.）的红色树脂，在中国传统医学中已被用于治疗急性心肌梗死（AMI）数百年。有证据表明，DB 通过在心肌梗死期间抑制炎症反应可能发挥心脏保护作用。然而，其药物机制仍有待阐明。
研究目的
由于其潜在的抗炎作用，本研究中应用龙血树提取物（DBE）于 AMI 小鼠模型，并验证其通过 PI3K-AKT-mTOR 信号通路对炎症的作用机制。
材料和方法
通过结扎左前降支（LAD）建立 AMI 小鼠模型。在手术前 7 天给予 DBE 治疗。通过二维超声心动图评估心功能。检测血清中 CK-MB 和 LDH1 的水平以及血浆中 TXB2、6-酮-PGF1α 和 ET-1 的水平。通过 ELISA 定量检测心肌组织中 IL-6 的水平。通过 Western blot 检测 PI3K-AKT-mTOR 信号通路中关键蛋白的表达。
结果
结果表明，DBE 可改善 AMI 小鼠模型的心功能。同时，它还可以调节 CK-MB 和 LDH1 的水平，并恢复 TXB2 和 6-酮-PGF1α 之间的平衡。进一步的研究表明，DBE 可以抑制炎症并调节心肌组织中 IL-6-JAK2/STAT3 通路的关键蛋白表达。Western blot 结果验证了 DBE 可以激活 PI3K-AKT-mTOR 信号通路，从而调节其下游靶标，包括 VEGF、COX2 和 PPARγ 的表达。
结论
DBE 通过激活心肌组织中的 JAK2-STAT3 和 PI3K-AKT-mTOR 通路发挥心脏保护作用。这些发现为 DBE 的药理学机制提供了深入了解，并验证了 DBE 在 AMI 临床应用中的有益效果。
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