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落新妇苷对大鼠心肌缺血再灌注损伤的影响及机制
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陈兴华 ,韩 露 ,贡 鸣 ,张继倬 (1.首都医科大学附属北京世纪坛医院心脏外科,北京 100038;2.首都医
科大学附属朝阳医院医学研究中心,北京 100020;3.首都医科大学附属北京安贞医院心外科,北京 100029)
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2023)10-1193-07
DOI 10.6039/j.issn.1001-0408.2023.10.08
摘 要 目的 探究落新妇苷(AST)对大鼠心肌缺血再灌注损伤(MIRI)的影响,以及可能的作用机制。方法 将SD雄性大鼠随
机分为假手术组、模型组、阳性对照组(复方丹参片240 mg/kg)和AST低、高剂量组(30、90 mg/kg)以及AST高剂量+缺氧诱导因子
1α(HIF-1α)抑制剂组(AST 90 mg/kg+2-甲氧基雌二醇15 mg/kg),每组25只。除假手术组外,其他各组大鼠均建立MIRI模型,灌
胃或腹腔注射相应药物或生理盐水,连续28 d。测定各组大鼠血清中心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)含量,测量
心肌梗死体积比,观察心肌组织病理形态变化、心肌细胞凋亡率和心肌组织线粒体的超微结构,测定心肌组织中肿瘤坏死因子α
(TNF-α)、白细胞介素 6(IL-6)、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性以及 HIF-1α、腺病毒 E1B 相互作用蛋白 3
(BNIP3)、肌球蛋白样 Bcl-2 结合蛋白(Beclin1)的表达,并计算微管相关蛋白轻链 3(LC3)Ⅱ与Ⅰ的比值(简称“LC3Ⅱ/Ⅰ”)。
结果 与模型组比较,阳性对照组和AST低、高剂量组大鼠的心肌组织无明显肿胀,心肌纤维排列整齐,心肌梗死体积比和cTnI、
CK-MB、TNF-α、IL-6、MDA含量以及细胞凋亡率均显著降低(P<0.05),SOD活性和HIF-1α、BNIP3、Beclin1蛋白表达量以及LC3
Ⅱ/Ⅰ均显著升高(P<0.05)。HIF-1α抑制剂可显著削弱AST对MIRI模型大鼠上述指标的改善作用(P<0.05)。结论 AST可以
通过激活HIF-1α/BNIP3信号通路来增强线粒体自噬,从而减轻大鼠MIRI。
关键词 落新妇苷;心肌缺血再灌注损伤;缺氧诱导因子1α;B细胞淋巴瘤2/腺病毒E1B相互作用蛋白3;自噬
Effects and mechanism of astilbin on myocardial ischemia-reperfusion injury in rats
CHEN Xinghua ,HAN Lu ,GONG Ming ,ZHANG Jizhuo (1. Dept. of Cardiac Surgery, Beijing Shijitan
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Hospital Affiliated to Capital Medical University,Beijing 100038,China;2. Medical Research Center, Beijing
Chaoyang Hospital Affiliated to Capital Medical University,Beijing 100020,China;3. Dept. of Cardiac Surgery,
Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029,China)
ABSTRACT OBJECTIVE To investigate the effects of astilbin (AST) on myocardial ischemia-reperfusion injury (MIRI) in rats
and its potential mechanism. METHODS SD male rats were randomly divided into sham operation group, model group, positive
control group (Compound Salvia miltiorrhiza tablets, 240 mg/kg), AST low-dose and high-dose groups (30, 90 mg/kg), and high-
dose of AST+hypoxia-inducible factor-1α(HIF-1α) inhibitor group (AST 90 mg/kg+2ME2 15 mg/kg), with 25 rats in each group.
Except for sham operation group, MIRI model was induced in other groups, and then given relevant drug or normal saline
intragastrically or intraperitoneally, for consecutive 28 d. Serum contents of cardiac troponin I (cTnI) and creatine kinase
isoenzyme (CK-MB) were detected; volume ratio of myocardial infarction was measured; the pathological changes of
myocardium, the apoptotic rate of myocardial cells and ultrastructure of mitochondria in myocardial tissue were all observed. The
contents of tumor necrosis factor α (TNF- α), interleukin 6 (IL-6) and malondialdehyde (MDA), the activity of superoxide
dismutase (SOD), the expressions of HIF-1α, adenovirus E1B interacting protein 3 (BNIP3) and myosin-like Bcl-2 interacting
protein (Beclin1) were determined in myocardium. The ratio of microtubule-associated protein light chain 3 (LC3) Ⅱ to Ⅰ (LC3
Ⅱ/Ⅰ) in rat myocardium was calculated. RESULTS Compared with model group, no obvious swelling was found in the
myocardial tissue of rats in positive control group, AST low-dose and high-dose groups, and the myocardial fibers were arranged
regularly; the volume ratio of myocardial infarction, the contents of cTnI, CK-MB, TNF-α, IL-6 and MDA, the apoptotic rate
were decreased significantly (P<0.05), while SOD activity, protein expressions of HIF-1α, BNIP3 and Beclin1, LC3Ⅱ/Ⅰ were
increased significantly (P<0.05). HIF-1α inhibitor could significantly weaken the improvement effect of AST on the above
indicators in MIRI model rats (P<0.05). CONCLUSIONS AST enhances mitochondrial autophagy by activating HIF-1α/BNIP3
signaling pathway, thereby reducing MIRI in rats.
Δ 基金项目 国家自然科学基金资助项目(No.81770466) KEYWORDS astilbin; myocardial ischemia-reperfusion
*第一作者 主治医师,硕士。研究方向:心肌缺血再灌注损伤。 injury; hypoxia-inducible factor-1α; B-cell lymphoma-2/
E-mail:sjtxzwk@163.com adenovirus E1B interacting protein 3; autophagy
# 通信作者 主任医师,硕士。研究方向:心肌缺血再灌注损伤。
E-mail:13911028861@163.com
中国药房 2023年第34卷第10期 China Pharmacy 2023 Vol. 34 No. 10 · 1193 ·