心阴片通过MLK3调控巨噬细胞M1极化对慢性心力衰竭心肌纤维化的机制研究  

Study on the mechanism of Xinyin Tablet regulating macrophage M1 polarization through MLK3 on myocardial fibrosis in chronic heart failure

作　　者：郭依宁 刘青 王俊岩[1,2,3,4] 冼绍祥 杨忠奇[1,2,3,4] 叶小汉 王婷[5] 王陵军 黄育生 GUO Yi-ning;LIU Qing;WANG Jun-yan;XIAN Shao-xiang;YANG Zhong-qi;YE Xiao-han;WANG Ting;WANG Lingjun;HUANG Yu-sheng(The First Afiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;First School of Clinic Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Lingnan Medical Research Center,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Guangdong Provincial Universities Key Laboratory of Chinese Medicine Prevention and Treatment of Chronice Heart Failure,Guangzhou 510405,China;Dongguan TCM Hospital of Guangzhou University of Chinese Medicine,Guangdong 523127,China)

机构地区：[1]广州中医药大学第一附属医院,广州510405 [2]广州中医药大学第一临床医学院,广州510405 [3]广州中医药大学岭南医学研究中心,广州510405 [4]广东省普通高校慢性心力衰竭中医药防治重点实验室,广州510405 [5]广州中医药大学东莞医院,东莞523127

出　　处：《中华中医药杂志》2022年第10期5899-5903,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81804048,No.81973776,No.81973777);广州市科技局计划项目(No.202102020123);广州市重点实验室项目(No.201705030006);广东省普通高校慢性心力衰竭中医药防治重点实验室。

摘　　要：目的:观察心阴片调控混合谱系激酶3(MLK3)对慢性心力衰竭(CHF)心肌纤维化的作用。方法:将C57BL/6J小鼠随机分为假手术组,模型组,心阴片低、中、高剂量组、培哚普利组,每组25只。构建压力负荷小鼠模型并连续给药1周,进行心脏超声检测。通过组织病理学染色观察心肌胶原纤维改变,RT-qPCR、Western Blot检测基质金属蛋白酶2(MMP2)、白细胞介素-6(IL-6)、CollagenⅠ、CollagenⅢmRNA和MLK3、α-平滑肌肌动蛋白(α-SMA)、诱导型一氧化氮合酶(iNOS)、IL-6、肿瘤坏死因子-α(TNF-α)蛋白表达情况。结果:与模型组比较,心阴片各组及培哚普利组小鼠心功能显著提高(P<0.05),炎症细胞浸润减少、纤维化程度降低,纤维化及炎症因子相关蛋白MLK3、α-SMA、iNOS、IL-6、TNF-α和MMP2、IL-6、CollagenⅠ、CollagenⅢmRNA表达显著下降(P<0.05)。结论:心阴片能抑制心肌纤维化改善CHF小鼠疾病进展,其机制可能通过MLK3调控巨噬细胞M1极化发挥作用。Objective: To observe the effects of Xinyin Tablet regulating mixed lineage kinases 3(MLK3) on myocardial fibrosis in chronic heart failure. Methods: C57BL/6J mice were randomly divided into sham, model, perindopril, Xinyin Tablet low, medium and high dose groups, 25 in each group. The mouse model of aortic coarctation was constructed and administered continuously for 1 week. Cardiac ultrasound was performed. The changes of myocardial collagen fibers were observed by histopathological staining. RT-qPCR and Western Blot detected the expression of MMP2, IL-6, Collagen Ⅰ, Collagen ⅢmRNA and α-SMA, iNOS, IL-6, TNF-α protein. Results: Compared with the model group, the heart function was significantly improved(P<0.05), and the degree of inflammation, fibrosis were reduced, and the expression of fibrosis related α-SMA, iNOS,IL-6, TNF-α protein and MMP2, IL-6, Collagen Ⅰ, Collagen Ⅲ mRNA were significantly decreased in Xinyin Tablet groups(P<0.05). Conclusion: Xinyin Tablet can inhibit myocardial fibrosis and improve the heart function of CHF mice. The mechanism may be that MLK3 regulates the polarization of macrophages M1.

关 键 词：心力衰竭 心肌纤维化 巨噬细胞 心阴片 混合谱系激酶3(MLK3) 

分 类 号：R285[医药卫生—中药学]