贯叶连翘提取物对小鼠免疫性心肌炎心肌纤维化的影响及其机制*

doi:10.12047/j.cjap.5822.2019.087

摘要/Abstract

摘要： 目的:研究贯叶连翘提取物(HPE)对小鼠实验性免疫性心肌炎心肌纤维化(MFEAM)的影响。方法:利用猪心肌肌球蛋白免疫易感鼠系,建立小鼠MFEAM模型,将MFEAM模型组小鼠随机分为: MFEAM模型组(n=14)、HPE100 mg/kg组(n=13)、HPE 40 mg/kg组(n=13)、Cap 50 mg/kg对照组(n=13)。各组药物每次均分别以0.4 ml生理盐水溶解,采用灌胃给药方式,每天2次,共60 d;正常对照组(n=10),MFEAM模型组按上述方法同体积同疗程给予生理盐水。通过观察小鼠一般情况,测定心脏重量、脾脏重量与体重之比,检测小鼠血清中I型前胶原N端前肽(PINP)、III型前胶原N端前肽(PIIINP)含量及转化生长因子-β1(TGF-β1)浓度,Masson染色显微镜观察心肌纤维化(MF)程度及胶原容积分数(CVF)测定,Western blot检测心肌TGF-β1蛋白表达。结果:MFEAM模型组小鼠血清中TGF-β1浓度及PINP、PIIINP含量显著升高,MF程度及CVF增加,心肌TGF-β1蛋白表达上调,与正常组比较差异有显著性意义(P＜0.05或P＜0.01);而HPE 40 mg/kg、100 mg/kg及Cap对照组血清PINP、PIIINP含量及TGF-β1浓度均减少,不同HPE或Cap剂量显著改善或降低MFEAM模型小鼠MF程度及CVF,不同程度下调心肌TGF-β1蛋白表达水平,与MFEAM模型组比较差异有显著性意义(P＜0.05或P＜0.01)。结论:HPE对MF有治疗作用,可能与其减少胶原蛋白沉积,抑制TGF-β1信号通路有关。

关键词: 贯叶连翘提取物, 心肌纤维化, I型前胶原N端前肽、III型前胶原N端前肽, 转化生长因子-β1通路, 小鼠

Abstract: Objective: To study the effects of hypericum perforatum extract (HPE) on myocardial fibrosis of the experimental autoimmune myocarditis (MFEAM) in mice. Methods: MFEAM model of immunosuppressive mouse was established by porcine cardiac myosin. The mice in the MFEAM model group were randomly divided into: MFEAM model group (n=14), HPE 100 mg/kg group (n=13), HPE 40 mg/kg group (n=13) and captopril (Cap) 50 mg/kg control group (n=13). Drug in each group was dissolved in 0.4 ml of physiological saline each time, and administered by intragastric administration twice a day for 60 days; the normal control group (n=10) and the MFEAM model group was given normal saline at the same volume and course of treatment as above described way. The ratio of heart weight and spleen weight to body weight were calculated, the general conditions of mice were observed. The contents of procollagen I N-terminal peptide(PINP), procollagen III N-terminal peptide (PIIINP) and TGF-β1 in serum of mice were detected. The degree of myocardial fibrosis (MF) and collagen volume fraction (CVF)were measured under the microscope by Masson staining. The protein expression of TGF-β1 was detected by Western blot. Results: The serum levels of TGF-β1, PINP and PIIINP in the model group were higher than those in the normal group significantly (P＜0.05 or P＜0.01). Meanwhile , the levels of MF and CVF were increased, and the protein expression of myocardial TGF-β1 was up-regulated. However, the serum levels of PINP, PIIINP and TGF-β1 in HPE40 mg/kg, HPE 100 mg/kg and Cap treated-groups were decreased significantly. HPE and Cap could improve or decrease the MF level and CVF of the MFEAM model mice, and down-regulated the expression of TGF-β1 protein in different degrees. Compared with the MFEAM model group, the difference was significant (P＜0.05 or P＜0.01).Conclusion: HPE has a therapeutic effect on MF, which may be related to its reduction of collagen deposition and inhibition of TGF-β1 signaling pathway.

Key words: hypericum perforatum extract, myocardial fibrosis, PINP, PIIINP, TGF-β1 pathway, mice

傅艳菲, 李乐, 童盛强, 颜继忠. 贯叶连翘提取物对小鼠免疫性心肌炎心肌纤维化的影响及其机制^*[J]. 中国应用生理学杂志, 2019, 35(5): 402-405.

FU Yan-fei, LI Le, TONG Sheng-qiang, YAN Ji-zhong. Effects of hypericum perforatum extract on the immunogenic myocardial fibrosis in mice and its mechanism[J]. CJAP, 2019, 35(5): 402-405.

参考文献

[1] Kindermann I, Barth C, Mahfoud F, et al. Update on myocarditis[J]. J Am Coll Cardiol, 2012, 59(9): 779-792.
[2] 丁国雷, 韩丽娜, 王玉堂, 等. 一氧化氮合酶抑制剂治疗实验性自身免疫性心肌炎的研究[J]. 中国应用生理学杂志, 2013, 29(2): 195-163.
[3] Passino C, Barison A, Vergaro G, et al. Markers of fibrosis, inflammation, and remodeling pathways in heart failure[J]. Clinica Chimica Acta, 2015, 443: 29-38.
[4] Yi C, Wang SJ.Hypericin, the active component of St.John’s wort, inhibits glutamate release in the rat cerebrocortical synaptosomes via a mitiogen-activated protein kinase-dependent pathway[J]. Eur J Pharmacol, 2010, 634: 53-61.
[5] 李乐, 张益灵, 陶厚权. 贯叶连翘提取物对小鼠免疫性心肌炎的作用[J]. 中国应用生理学杂志, 2013, 29(4): 336-338.
[6] Akahori H, Tsujino T, Naito Y, et al. Atorvastatin ameliorates cardiac fibrosis and improves left ventricular diastolic function in hypertensive diastolic heart failure model rats[J]. J Hypertens, 2014, 32(7): 1534-1541.
[7] Leuschner F,Katus HA,Kaya Z.Autoimmune myocarditis: past, present and future[J]. J Autoimmun, 2009, 33(3-4): 282-289.
[8] Querejeta R, Lopez B, Gonzalez A, et al.Increased collagen type I synthesis in patients with heart failure of hypertensiveorigin: relation to myocardial fibrosis[J]. Circulation, 2004, 110(10): 1263-1268.
[9]Lepojärvi ES, Piira OP, Pääkkö E, et al. Serum PINP, PIIINP, galectin-3, and ST2 as surrogates of myocardial fibrosis and echocardiographic left venticular diastolic filling properties[J]. Front Physiol, 2015, 6: 200-206.
[10]陈姝. 卡托普利药物的应用及作用机制分析[J]. 临床医药文献杂志, 2016, 3(1): 189-191.
[11]Duan Y, Zhu W, Liu M, et al. The expression of Smad signaling pathway in myocardium and potential therapeutic effects[J]. Histol Histopathol, 2017, 32(7): 651-659.
[12]裴宸晨, 李乐. 贝母提取物对异丙肾上腺素致小鼠心肌纤维化的作用[J]. 中国应用生理学杂志, 2018, 34(1): 48-49.
[13]Dobaczewski M, Chen W, Frangogiannis NG.Transforming growth factor(TGF)-β signaling in cardiac remodeling[J]. J Mol Cell Cardiol, 2011, 51(4): 600-606.

[1]	扈敬, 李法东, 邵小婷, 李思葳, 张欣颖, 赵冰冰, 徐长庆, 魏璨. 精胺对高糖引起的大鼠心肌纤维化的影响及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 193-196.
[2]	邵小婷, 扈敬, 张欣颖, 赵冰冰, 李思葳, 高萍, 徐长庆, 魏璨. 外源性精胺对糖尿病肾病小鼠肾纤维化的影响及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 207-210.
[3]	刘凯丽, 都新新, 张文琴, 吴亚俐, 王茜, 王春芳, 崔香丽. 过表达miR-31对结肠炎模型小鼠TLR4/NF-κB信号通路及凋亡蛋白的调控[J]. 中国应用生理学杂志, 2020, 36(3): 211-215.
[4]	卢林明, 俞婷婷, 何晓伟, 汤娟, 李先伟. 小剂量辣椒素抗小鼠肺纤维化的作用及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 216-222.
[5]	姜洪波, 董家行, 秦玉飞, 刘佳聪, 姜万举, 李若男, 刘岚慈, 田一丹, 许予明, 杜爱林. 硫氢化钠对脊髓小脑共济失调3型小鼠海马MBP及学习记忆的影响[J]. 中国应用生理学杂志, 2020, 36(3): 235-239.
[6]	方振, 胡西厚, 李康, 韩洁, 田蕾, 闫峻, 张伟, 来文庆, 林本成, 刘晓华, 袭著革. PM_2.5鼻腔滴注致小鼠海马组织损伤的炎性机制[J]. 中国应用生理学杂志, 2020, 36(3): 240-244.
[7]	王锋, 张海峰. 利拉鲁肽联合维生素D对高脂诱导非酒精性脂肪肝小鼠的影响及机制[J]. 中国应用生理学杂志, 2020, 36(3): 261-264.
[8]	姚楠, 韦凌霞, 王志旺, 丁茂鹏, 付晓艳, 庞亚蓉, 程小丽, 蔺兴遥, 邵晶. 当归对阴虚哮喘小鼠气道黏液高分泌及TNF-α/NF-κB信号通路的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 97-100.
[9]	霍海燕, 王瑾, 张许梅, 张文婷, 岳继萍, 焦向英. 糖尿病诱导硫氧还蛋白相互作用蛋白(TXNIP)对小鼠胰岛β细胞衰老的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 119-123.
[10]	罗维, 艾磊, 王博发, 王俐颖, 甘彦明, 周越. 高糖条件下小鼠巨噬细胞对骨骼肌细胞成肌分化和胰岛素敏感性的影响^*[J]. 中国应用生理学杂志, 2020, 36(2): 124-129.
[11]	赵洋, 杨胜昌, 于富洋, 李文雅, 吉恩生. 消痰化瘀利窍方对慢性间歇性低氧小鼠认知障碍的改善作用^*[J]. 中国应用生理学杂志, 2020, 36(2): 143-147.
[12]	梁宛伶, 肖天保, 袁峰, 曹一波, 颜登国. miRNA-95靶向FOXD1基因对结直肠癌LoVo细胞放射敏感性的影响及其机制^*[J]. 中国应用生理学杂志, 2020, 36(2): 148-151.
[13]	罗怡爽, 郑秀婷, 章浩月, 徐丽萍, 裘加鹏, 徐港铭, 刘爱明. α-荼异硫氰酸酯诱导小鼠胆汁淤积性肝纤维化及其炎症通路^*[J]. 中国应用生理学杂志, 2020, 36(2): 152-156.
[14]	罗金定, 伍迪, 吕慧婕, 何剑琴, 杨丝丝, 奉水东, 凌宏艳. 二氢杨梅素对高脂饮食诱导的小鼠肥胖的影响及其机制[J]. 中国应用生理学杂志, 2020, 36(1): 6-11.
[15]	卢漫漫, 陈家耀, 钮鸣宇, 吴卫东. 有氧运动对高脂饮食小鼠肝脏中CLK2蛋白表达的影响[J]. 中国应用生理学杂志, 2020, 36(1): 23-26.

贯叶连翘提取物对小鼠免疫性心肌炎心肌纤维化的影响及其机制^*

Effects of hypericum perforatum extract on the immunogenic myocardial fibrosis in mice and its mechanism

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价