摘要
目的探讨天香丹对冠状动脉微循环障碍的影响及可能作用机制。方法63只SD大鼠随机分为空白对照组、假手术组、模型组、尼可地尔组和天香丹低、中、高剂量组,每组9只。除空白对照组外,其余各组大鼠开胸后左心室内注射月桂酸钠建立冠状动脉微循环障碍大鼠模型,假手术组注射生理盐水。造模后天香丹低、中、高剂量组大鼠分别给予天香丹颗粒0.1188、0.2376、0.4752g/(kg·d)灌胃;尼可地尔组给予尼可地尔原药粉0.297mg/(kg·d)灌胃;空白对照组、假手术组、模型组给予生理盐水2ml灌胃,均每日1次,共28天。检测各组大鼠心功能,采用HE、马休黄-酸性品红-苯胺蓝染色进行冠状动脉微血管病理学观察,观察心肌组织超微结构,并检测心肌组织中Nrf2/ARE信号通路蛋白[包括核转录因子E2相关因子2(Nrf2)、Kelch样环氧氯丙烷相关蛋白1(Keap1)、醌氧化还原酶1(NQO1)、氧化氢酶(CAT)、血红素加氧酶1(HO-1)]表达。结果病理结果显示,模型组大鼠冠状动脉微血管内可见血栓混合物,心肌细胞纤维化,微血栓程度较重,而各给药组微血栓程度降低,仅有少量微血栓。与空白对照组比较,假手术组及模型组大鼠心功能降低(P<0.05),心肌组织Nrf2、Keap1、NQO1、CAT、HO-1表达差异无统计学意义(P>0.05)。与模型组比较,尼可地尔组和天香丹中、高剂量组大鼠心功能好转,天香丹中、高剂量组心肌组织Nrf2、NQO1、CAT、HO-1蛋白表达升高(P<0.05);且天香丹中剂量组心肌组织Nrf2、NQO1、CAT及天香丹高剂量组HO-1表达高于尼可地尔组(P<0.05)。结论天香丹能够减轻微血栓及线粒体损伤程度,从而改善冠状动脉微循环障碍,其机制可能与调控Nrf2/ARE信号通路从而减轻氧化应激有关。
Objective To explore the effect of Tian Xiang Dan(天香丹)on coronary microcirculation dysfunction(CMD)and its possible mechanism.Methods Sixty-three SD rats were randomly divided into a blank control group,a sham operation group,a model group,a nicorandil group and Tian Xiang Dan low,medium and high dose groups,with nine rats in each group.The model of CMD was established in all rats except for the blank control group,by injecting normal saline(for sham operation group)or sodium laurate(for other groups)into the left ventricle after thoracotomy.After modeling,Tian Xiang Dan at a dosage of 0.1188 g/(kg·d),0.2376 g/(kg·d),and 0.4752 g/(kg·d)was administered by gavage in Tian Xiang Dan low,medium and high dose groups,respectively;0.297 mg/(kg·d)nicorandil powder by gavage was administered in nicorandil group;the blank control group,the sham operation group,and the model group were given 2 mL normal saline by gavage;all administrations were performed once per day,for 28 days.Cardiac function was detected in all the rats.Hematoxylin and eosin(HE)stain and martius yellow-acid fuchsin-aniline blue stain were used to observe the pathological changes in the capillary blood vessels of coronary circulation.The ultrastructure of the myocardial tissues was investigated;the expression of nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway proteins,including Nrf2,Kelch-like epichlorohydrin-associated protein 1(Keap1),quinone oxidoreductase 1(NQO1),catalase(CAT),heme oxygenase-1(HO-1)were determined.Results In model group,there was thromboembolism in capillary blood vessels;myocardial cells showed fibrosis;and microthrombosis was severe,while in other treatment groups,the degree of thrombosis was light with only few microthrombi.Compared to the blank control group,the cardiac function in sham operation group and model group decreased significantly(P<0.05),while no significant differences were found between groups in the expression of Nrf2,Keap1,NQO1,CAT and HO-1(P>0.05).Compared to the model group,the cardiac function significantly improved in nicorandil group and Tian Xiang Dan medium and high dose groups(P<0.05);and the expression levels of Nrf2,NQO1,CAT,and HO-1 proteins significantly increased in Tian Xiang Dan medium and high dose groups(P<0.05).Compared to nicorandil group,there was higher expression levels of Nrf2,NQO1,CAT proteins in Tian Xiang Dan medium group,and higher expression level of HO-1 protein in Tian Xiang Dan high group(P<0.05).Conclusion Tian Xiang Dan can alleviate microthrombosis and mitochondrial damage,thereby improving coronary microcirculation dysfunction.The underlying mechanism may be related to Nrf2/ARE signaling pathway through which oxidative stress is reduced.
作者
马学宽
古丽葛娜·萨吾尔
张亚洁
辛锦钰
张华
王思静
安冬青
MA Xuekuan;GULIGENA•Sawuer;ZHANG Yajie;XIN Jinyu;ZHANG Hua;WANG Sijing;AN Dongqing(Institute of Traditional Chinese Medicine,Xinjiang Medical University,Urumqi,830011)
出处
《中医杂志》
CSCD
北大核心
2021年第3期246-251,共6页
Journal of Traditional Chinese Medicine
基金
国家自然科学基金(81760843)。
作者简介
通讯作者:安冬青,andongqing3@gmail.com,13609920771。
