Zhao Yu, Tian Xuefeng, Liu Gengfeng, Wang Kuijing, Xie Yuanyuan, Qiu Yuxuan
Cadre Ward, The First Hospital of Harbin, Harbin, Heilongjiang 150010, P.R. China.
Department of Cardiology, Heilongjiang Provincial Hospital, Harbin, Heilongjiang 150056, P.R. China.
Exp Ther Med. 2019 Jan;17(1):230-236. doi: 10.3892/etm.2018.6949. Epub 2018 Nov 9.
Ischemic heart disease is a leading cause of mortality and occurs due to coronary arterial atherosclerosis, vascular cavity stenosis and occlusion. It has previously been demonstrated that berberine treatment may ameliorate and help to prevent cardiovascular diseases due to its anti-inflammatory and anti-apoptotic effects in myocardial cells. However, the potential signaling mechanisms mediated by berberine in the progression of myocardial injury remain to be elucidated. The aim of the present study was to investigate the therapeutic effects of berberine and its potential mechanism in a mouse model of myocardial cell injury. The results revealed that berberine treatment downregulated the serum expression of inflammatory factors, including interleukin (IL)-6, tumor necrosis factor-α, IL-10 and IL-17A in mice with anoxia-reoxygenation injury. Berberine treatment also decreased myocardial cell apoptosis following anoxia-reoxygenation injury via regulating the expression of apoptosis-associated genes. Histological analysis revealed that the area, circumference fragmentation and segmentation of myocardial cells were significantly decreased by berberine treatment compared with the control group. The body weight, blood lipid levels, blood pressure and heart rate were markedly improved in mice with anoxia-reoxygenation injury following berberine treatment compared with untreated mice. The expression of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB expression was downregulated in myocardial cells from in mice with anoxia-reoxygenation injury following berberine treatment compared with untreated mice. However, p38 MAPK overexpression ameliorated the berberine-induced decrease in NF-κB activity and expression, as well as the berberine-induced inhibition of myocardial apoptosis in myocardial cells isolated from experimental mice. In conclusion, the results of the present study indicate that berberine is able to decrease the expression of inflammatory cytokines expression and inhibit myocardial cell apoptosis via downregulating the p38 MAPK-mediated NF-κB signaling pathway. These results suggest that berberine may be an effective treatment for anoxia-reoxygenation injury.
缺血性心脏病是导致死亡的主要原因，其发生是由于冠状动脉粥样硬化、血管腔狭窄和闭塞。先前的研究表明，黄连素治疗可能因其对心肌细胞的抗炎和抗凋亡作用而改善并有助于预防心血管疾病。然而，黄连素在心肌损伤进展中所介导的潜在信号机制仍有待阐明。本研究的目的是探讨黄连素在小鼠心肌细胞损伤模型中的治疗作用及其潜在机制。结果显示，黄连素治疗可下调缺氧复氧损伤小鼠血清中炎性因子的表达，包括白细胞介素（IL）-6、肿瘤坏死因子-α、IL-10和IL-17A。黄连素治疗还通过调节凋亡相关基因的表达减少了缺氧复氧损伤后的心肌细胞凋亡。组织学分析显示，与对照组相比，黄连素治疗显著降低了心肌细胞的面积、周长破碎和分割。与未治疗的小鼠相比，黄连素治疗后缺氧复氧损伤小鼠的体重、血脂水平、血压和心率均有明显改善。与未治疗的小鼠相比，黄连素治疗后缺氧复氧损伤小鼠心肌细胞中p38丝裂原活化蛋白激酶（MAPK）和核因子（NF）-κB的表达下调。然而，p38 MAPK的过表达改善了黄连素诱导的NF-κB活性和表达的降低，以及黄连素诱导的实验小鼠分离心肌细胞中细胞凋亡的抑制。总之，本研究结果表明，黄连素能够通过下调p38 MAPK介导的NF-κB信号通路来降低炎性细胞因子的表达并抑制心肌细胞凋亡。这些结果表明，黄连素可能是治疗缺氧复氧损伤的有效药物。
