
浏览全部资源
扫码关注微信
1.北京中医药大学生命科学学院,北京 102401
2.北京中医药大学第三附属医院心内科,北京 100029
马鑫,男,40岁,本科,实验师。研究方向:心血管疾病的中医基础研究。
李平,E-mail:pearll2008@126.com
纸质出版日期:2024-11-25,
收稿日期:2023-12-05,
移动端阅览
马鑫,戴方圆,张启明,等.小檗碱通过Notch信号通路改善心肌梗死大鼠心肌纤维化的作用机制[J].北京中医药,2024,43(11):1281-1286.
MA Xin,DAI Fangyuan,ZHANG Qiming,et al.Action mechanism of berberine for myocardial fibrosis improvement of rats with myocardial infarction via Notch signaling pathway[J]. Beijing Journal of Traditional Chinese Medicine,2024,43(11):1281-1286.
马鑫,戴方圆,张启明,等.小檗碱通过Notch信号通路改善心肌梗死大鼠心肌纤维化的作用机制[J].北京中医药,2024,43(11):1281-1286. DOI: 10.16025/j.1674-1307.2024.11.012.
MA Xin,DAI Fangyuan,ZHANG Qiming,et al.Action mechanism of berberine for myocardial fibrosis improvement of rats with myocardial infarction via Notch signaling pathway[J]. Beijing Journal of Traditional Chinese Medicine,2024,43(11):1281-1286. DOI: 10.16025/j.1674-1307.2024.11.012.
目的
2
探讨小檗碱对心肌梗死(MI)大鼠心肌纤维化改善的作用机制。
方法
2
将60只大鼠用随机数字表法取10只作为假手术组,其余50只采用冠状动脉结扎法制备MI模型。将造模成功的40只大鼠用随机数字表法分为模型组、美托洛尔组、小檗碱低剂量组和小檗碱高剂量组,每组10只。造模48 h后,小檗碱低剂量组、高剂量组分别给予小檗碱50、100 mg/kg灌胃,美托洛尔组给予美托洛尔10 mg/kg灌胃,假手术组、模型组给予生理盐水2 mL/d灌胃,1次/d,共干预30 d。记录各组体质量,HE染色后观察心肌组织病理变化,用天狼星红染色法检测心肌组织中胶原纤维含量,用免疫组化染色法检测心肌组织中基质金属蛋白酶1(MMP-1)、MMP-9蛋白,用Western blotting法检测心肌组织中Notch通路关键蛋白(Hey1、Hes1)、神经生长因子(NGF)、α-平滑肌肌动蛋白(α-SMA)蛋白。
结果
2
与假手术组比较,模型组各时间点体质量低(
P
<
0.05)。与模型组比较,给药组各时间点体质量高(
P
<
0.05)。假手术组大鼠心肌组织未见异常变化。模型组大鼠心肌组织紊乱,心肌细胞变性、坏死明显,细胞间质水肿明显,有大量炎性细胞浸润。各治疗组心肌细胞变性坏死得到改善,且小檗碱高剂量组改善最显著。与假手术组比较,模型组心肌组织中胶原纤维含量高(
P
<
0.05);与模型组比较,美托洛尔组、小檗碱低剂量组、小檗碱高剂量组心肌组织中胶原纤维含量均低(
P
<
0.05)。与假手术组比较,模型组大鼠心肌组织中MMP-1、MMP-9蛋白表达量高(
P
<
0.05);与模型组比较,美托洛尔组、小檗碱低剂量组、小檗碱高剂量组MMP-1、MMP-9蛋白表达均低(
P
<
0.01)。与假手术组比较,模型组大鼠心肌组织中Hes1、Hey1、NGF、α-SMA蛋白表达高(
P
<
0.05);与模型组比较,美托洛尔组、小檗碱高剂量组、小檗碱低剂量组Hes1、Hey1、NGF、α-SMA蛋白表达均低(
P
<
0.01)。
结论
2
小檗碱可通过Notch信号通路抑制心肌梗死(MI)大鼠心肌纤维化。
Objective
2
To investigate the effect of berberine on improving myocardial fibrosis in rats with myocardial infarction (MI).
Methods
2
Among the 60 rats, according to the random number table method, ten were chosen as the sham operation group, with the remaining 50 adopted to build an MI model by utilizing the coronary artery ligation method. Then, the 40 successfully modeled rats were divided into the model group, metoprolol group, low-dose berberine group, and high-dose berberine group, with ten rats in each group. After modeling for 48 hours, gavage administration was conducted with berberine on the high-dose (50 mg/kg) and low-dose (100 mg/kg) berberine groups, metoprolol (10 mg/kg) on the metoprolol group, and physiological saline (2 mL/d) on the sham operation group and model group. The treatment was carried out once a day for 30 days. Additionally, the body mass of each group was recorded, and the pathological changes of cardiac muscular tissue after HE staining were observed, with the collagen fiber content in cardiac muscular tissue detected by Sirius red staining. The matrix metalloproteinase-1 (MMP-1) and MMP-9 proteins in cardiac muscular tissue were detected by immunohistochemistry staining, and the key proteins of the Notch pathway (Hey1 and Hes1), nerve growth factor (NGF), and α smooth muscle actin (α-SMA) proteins in cardiac muscular tissue were also detected by Western blotting.
Results
2
The model group had lower body mass at all time points than the sham operation group (
P
<
0.05), and compared with the model group, the administration groups’ body mass at all time points was higher (
P
<
0.05). Meanwhile, there was no abnormal change in the cardiac muscular tissue of rats in the sham operation group. The cardiac muscular tissue of rats in the model group was disordered, and c
ardiac muscle cells had obvious degeneration and necrosis, with notable edema in intercellular substances and abundant inflammatory cell infiltration. The degeneration and necrosis of each treatment group were improved in treatment groups, with the most remarkable improvement in the high-dose berberine group. Compared with the sham operation group, the collagen fiber content in the cardiac muscular tissue of the model group was higher (
P
<
0.05), while that of the metoprolol group, low-dose berberine group, and high-dose berberine group was lower than the collagen fiber content of the model group (
P
<
0.05). Compared with the sham operation group, the expression of MMP-1 and MMP-9 proteins in the cardiac muscular tissue of rats in the model group was higher (
P
<
0.05), while that of MMP-1 and MMP-9 proteins in the metoprolol group, high-dose berberine group and low-dose berberine group was lower than that of the model group (
P
<
0.01). Compared with the sham operation group, the expression of Hes1, Hey1, NGF, and a-SMA proteins in the cardiac muscular tissue of rats in the model group was higher (
P
<
0.05). Compared with the model group, the expression of Hes1, Hey1, NGF, and α-SMA proteins in the metoprolol group, high-dose berberine group, and low-dose berberine group was lower (
P
<
0.01).
Conclusion
2
Berberine can inhibit myocardial fibrosis of MI rats via the Notch signaling pathway.
心肌梗死小檗碱纤维化Notch信号通路大鼠
Myocardial infarctionberberinefibrosisNotch signaling pathwayrat
TALMAN V, RUSKOAHO H. Cardiac fibrosis in myocardial infarction-from repair and remodeling to regeneration[J]. Cell Tissue Res, 2016,365(3):563-581.
MARIA SRF, ALESSANDRO DSRC, et al. Fibrosis after myocardial infarction: an overview on cellular processes, molecular pathways, clinical evaluation and prognostic value[J]. Med Sci (Basel), 2021,9(1):16.
宋晶,刘爱东,郭家娟,等.卡托普利通过下调α-平滑肌肌动蛋白、波形蛋白、人单丝氨酸蛋白激酶抑制心肌纤维化[J].中国老年学杂志,2020,40(5):1040-1044.
赵云阁,欧尔比特·安尼瓦尔,祝诚.细胞外基质与基质金属蛋白酶[J].生物化学与生物物理进展,1999,26(3):223-227.
HASAN W, JAMA A, DONOHUE T, et al. Sympathetic hyperinnervation and inflammatory cell NGF synthesis following myocardial infarction in rats[J]. Brain Res, 2006,1124(1):142-154.
金亮,庄仁玮,徐明彤,等.Notch1信号通路对AGEs诱导大鼠心脏肌成纤维细胞转分化的调控[J].岭南急诊医学杂志,2016,21(2):100-102.
解欣然,洪缨,董世芬.小檗碱抑制血管紧张素Ⅱ诱导的心肌成纤维细胞增殖和胶原合成的作用及机制研究[J].北京中医药大学学报,2008,31(11):748-751.
YU XH, WANG YF, DAI FY, et al.The protective effects of Berberine and Hesperidin on inflammatory factor-stimulating cardiac fibroblasts[J]. Eur Rev Med Pharmacol Sci, 2019,23:5468-5476.
张东伟,余文军,李娜,等.Notch1信号通路与心肌梗死小鼠心肌间质纤维化的关系研究[J].实用心脑肺血管病杂志,2016,24(11):4.
徐旖旎,陈婷婷,杨非,等.氧化苦参碱对醛固酮诱导大鼠心肌纤维化的作用及机制[J].贵州医科大学学报,2022,47(1):38-44.
沈明,郭志福,鲍礼智,等.大鼠心梗后心衰模型的制备及心功能评价[J].实验动物科学,2017,34(2):66-70.
张凯,谢世阳,王幼平,等.冠脉结扎法建立大鼠急性心肌梗死模型方法的探讨[J].中国中医急症,2014,23(8):1397-1399,1402.
刘剑刚,寇娜,熊双,等.冠心Ⅱ号提取工艺改进及其对急性心肌梗死大鼠心脏功能的影响[J].中国中西医结合杂志,2021,41(10):1206-1213.
姚德山,张振刚,龚开政.心肌梗死后心肌纤维化的研究进展[J].中华临床医师杂志(电子版),2018,12(2):103-106.
TOMASEK JJ, GABBIANI G, HINZ B, et al. Myofibroblasts and mechano-regulation of connective tissue remodelling[J]. Nat Rev Mol Cell Biol, 2002,3(5):349-363.
YIN J, HU H, LI X, et al. Inhibition of Notch signaling pathway attenuates sympathetic hyperinnervation together with the augmentation of M2 macrophages in rats post-myocardial infarction[J]. Am J Physiol Cell Physiol, 2016,310(1):C41-C53.
ZHOU XL, FANG YH, WAN L, et al. Notch signaling inhibits cardiac fibroblast to myofibroblast transformation by antagonizing TGF-β1/Smad3 signaling[J]. J Cell Physiol, 2019,234(6):8834-8845.
于立明,赵国龙,金振晓,等.小檗碱减轻大鼠心肌缺血再灌注损伤及其对Notch1/Hes1信号通路的调控研究[J].中国体外循环杂志,2015,13(4):240-244.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备 11010102006710号