| Objective: To study the effect of Tianxiangdan on Nrf2 / ARE signal pathway and its downstream factors in rats with coronary microcirculation dysfunction,and to explore its mechanism of improving coronary microcirculation dysfunction.Methods:(1)63 SPF male SD rats were randomly divided into seven groups: blank control group,sham operation group,model group,nicorandil group,Tianxiangdan low dose group,middle dose group and high dose group.In addition to the blank control group,rats were injected with sodium laurate into the left ventricle after thoracotomy to establish a model of coronary microcirculation dysfunction,while rats in the sham operation group were injected with normal saline.Rats in each group were given normal saline,Tianxiangdan and nicorandil for 28 days.(2)At the end of the experiment,echocardiography was used to observe the cardiac function,HE staining and Improved Lendrum staining were used to observe the morphological changes of coronary microvasculature,and transmission electron microscopy was used to observe the ultrastructural changes of myocardial cells.(3)The contents of MDA,SOD and GSH-Px in serum of each group were detected.(4)RT-qPCR and Western blot were used to observe the expression of Nrf2 / ARE signal pathway mRNA and protein in myocardium of rats in each group.Results:(1)the cardiac function of rats in nicorandil group,Tianxiangdan middle dose group and Tianxiangdan high dose group was better than that in model group(P<0.05).(2)After HE staining and Improved Lendrum staining,the red thrombus mixture was diffused in the coronary microvasculature of the model group,and local myocardial fibrosis was observed;the thrombus in the microvasculature of the nicorandil group and the Tianxiangdan low,medium and high dose groups were alleviated in varying degrees.The results of electron microscopy showed that the damage of myocardial ultrastructure in the model group was more obvious than that in the blank control group,and the damage of mitochondria in the nicorandil group and Tianxiangdan group was reduced.(3)The expression of MDA in the model group was higher than that in the blank control group and the sham operation group(P<0.05);the expression of MDA in the nicorandil group and Tianxiangdan group decreased after intervention(P<0.05);the expression of SOD in the nicorandil group increased(P<0.05);the expression of SOD and GSH-Px in the middle dose group and the high dose group of Tianxiangdan increased(P<0.05).(4)RT-qPCR and Western blot showed that the expression of Nrf2 / ARE signal pathway mRNA and protein in Tianxiangdan group was significantly higher than that in the model group,and there was a dose-dependent relationship.The expression of Nrf2,NQO1,CAT and HO-1 in the middle dose group and high dose group of Tianxiangdan was significantly increased(P<0.05);the expression of Nrf2,Keap1,CAT and HO-1 in the low dose group of Tianxiangdan was only different(P<0.05),and the expression of Nrf2 protein was increased(P<0.05);the expression of HO-1 mRNA was significantly increased after the intervention of nicorandil(P<0.05),but there was no significant difference in the protein expression of each factor(P>0.05).Conclusion: Tianxiangdan can reduce the degree of microthrombosis and mitochondrial damage,and promote the release of antioxidant factors.The mechanism of improving the ability of coronary microcirculation artery may associate with regulating Nrf2 / ARE signaling pathway to reduce oxidative stress. |
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