首页|瓜蒌薤白半夏汤通过chemerin/CMKLR1/PPARα信号通路干预2型糖尿病合并急性心肌梗死的作用

瓜蒌薤白半夏汤通过chemerin/CMKLR1/PPARα信号通路干预2型糖尿病合并急性心肌梗死的作用

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基于chemerin/趋化样因子受体 1(CMKLR1)/过氧化酶体增殖物激活受体(PPAR)α信号通路研究瓜蒌薤白半夏汤(GXBD)对 2 型糖尿病合并急性心肌梗死(T2DM-AMI)模型大鼠的干预作用,探讨GXBD对改善T2DM-AMI早期糖脂代谢紊乱现象的潜在机制。实验分为空白对照组(Ctrl)、模型组(T2DM-AMI)、阳性对照组(复方丹参片,DS)、瓜蒌薤白半夏汤高剂量组(GXBD-H)和瓜蒌薤白半夏汤低剂量组(GXBD-L)。采用灌胃高脂乳剂(HFE)和腹腔注射链脲佐菌素(STZ)的方法建立2 型糖尿病(T2DM)模型,然后冠状动脉结扎以诱导形成急性心肌梗死(AMI)。空白对照组和模型组灌胃等量生理盐水,各给药组给予相应药物灌胃。通过 ELISA 和生化检测评估相关代谢指标的变化,Western blot 分析肝脏、腹腔脂肪和心脏中chemerin、趋化样因子受体 1(CMKLR1)、过氧化物酶体增殖物激活受体α(PPARα)的蛋白表达。实验结果表明GXBD改善了T2DM-AMI的心脏病理损伤,降低了血脂、心肌酶和炎性因子水平,但对血糖变化不明显。此外,与模型组相比,GXBD降低了外周血中chemerin的表达,升高了肝脏中环磷酸腺苷(cAMP)和蛋白激酶A(PKA)的水平,且经GXBD治疗后肝脏、腹腔脂肪和心脏中chemerin、CMKLR1 蛋白表达水平降低,肝脏和腹腔脂肪中PPARα蛋白表达水平上升。以上研究结果说明GXBD可显著改善T2DM-AMI的糖脂代谢紊乱,进而对受损心肌具有保护作用。其机制可能与干预chemerin/CMKLR1/PPARα信号通路有关。这为临床进一步研究GXBD防治T2DM-AMI提供新的理论依据,也是中药治疗胸痹"痰浊壅塞"证候在蛋白水平的体现。
Gualou Xiebai Banxia Decoction treats type 2 diabetes mellitus combined with acute myocardial infarction via chemerin/CMKLR1/PPARα signaling pathway
This study aims to investigate the effects of Gualou Xiebai Banxia Decoction(GXBD)on type 2 diabetes mellitus(T2DM)combined with acute myocardial infarction(AMI)in rats via chemerin/chemokine-like receptor 1(CMKLR1)/peroxisome proliferator-activated receptor α(PPARα)signaling pathway,and to explore the mechanism of GXBD in alleviating glucose and lipid metabolism disorders.The SD rats were randomized into control,model,positive control,and low-and high-dose GXBD groups.The rat model of T2DM was established by administration with high-fat emulsion(HFE)by gavage and intraperitoneal injection with streptozotocin,and then coronary artery ligation was performed to induce AMI.The control and model groups were administrated with the equal volume of normal saline,and other groups were administrated with corresponding drugs by gavage.Changes in relevant metabolic indicators were assessed by ELISA and biochemical assays,and the protein levels of chemerin,CMKLR1,and PPARα in the liver,abdominal fat,and heart were determined by Western blot.The results showed that GXBD alleviated the myocardial damage and reduced the levels of blood lipids,myocardial enzymes,and inflammatory cytokines,while it did not lead to significant changes in blood glucose.Compared with the model group,GXBD down-regulated the expression of chemerin in peripheral blood and up-regulated the expression of cyclic adenosine monophosphate(cAMP)and protein kinase A(PKA)in the liver.After treatment with GXBD,the protein levels of chemerin and CMKLR1 in the liver,abdominal fat,and heart were down-regulated,while the protein levels of PPARα in the liver and abdominal fat were up-regulated.In conclusion,GXBD significantly ameliorated the disorders of glycolipid metabolism in the T2DM-AMI model by regulating the chemerin/CMKLR1/PPARα signaling pathway to exert a protective effect on the damaged myocardium.This study provides a theoretical basis for further clinical study of GXBD against T2DM-AMI and is a manifestation of TCM treatment of phlegm and turbidity causing obstruction at the protein level.

Gualou Xiebai Banxia Decoctiontype 2 diabetes mellitusacute myocardial infarctionchemerinCMKLR1PPARα

王蕾、官帅、吴梦雪、周慧、赵启韬、荀丽英

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山东中医药大学 药学院, 山东 济南 250355

山东中医药大学 中医学院, 山东 济南 250355

瓜蒌薤白半夏汤 2型糖尿病 急性心肌梗死 chemerin CMKLR1 PPARα

山东省自然科学基金项目

ZR2020MH342

2024

中国中药杂志
中国药学会

中国中药杂志

CSTPCD北大核心
影响因子:1.718
ISSN:1001-5302
年,卷(期):2024.49(6)
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