Exploring Mechanism of Heart and Brain Protection of Bukan Yilidan on a Rat Model of Perimenopausal Psycho-cardiac Disease Based on Mitochondrial Autophagy
10.13422/j.cnki.syfjx.20250863
- VernacularTitle:基于线粒体自噬探讨补坎益离丹对围绝经期双心病大鼠模型的心脑保护作用机制
- Author:
Ningyang XU
1
;
Xiande MA
1
;
Lu REN
1
;
Yuqing HU
1
Author Information
1. Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China
- Publication Type:Journal Article
- Keywords:
perimenopausal psycho-cardiac disease;
Yang deficiency of heart and kidneys;
Bukan Yilidan;
mitochondrial autophagy;
mitochondrial dynamics;
dynamin-related protein 1(Drp1)/phosphatase and tensin homolog(PTEN) induced putative kinase 1(PINK1)/Parkin pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(15):48-59
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect and mechanism of Bukan Yilidan on perimenopausal psycho-cardiac disease by mitochondrial autophagy mediated by dynamin-related protein 1(Drp1)/phosphatase and tensin homolog(PTEN) induced putative kinase 1(PINK1)/Parkin pathway. MethodsSixty rats were randomly divided into the blank group, model group, western medicine group(isosorbide mononitrate 7.2 mg·kg-1+sertraline hydrochloride tablets 18 mg·kg-1), Bukan Yilidan low, medium and high dose groups(2.59, 5.18, 10.35 g·kg-1), with 10 rats in each group. Except for the blank group, the rat model of perimenopausal psycho-cardiac disease was prepared by ovariectomy(OVX) combined with high-fat feeding, chronic unpredictable mild stress(CUMS) and subcutaneous multi-point injection of isoproterenol hydrochloride. After successful modeling, the general state and tongue image of rats were observed. The depression status of rats in vivo was evaluated by open field test, sucrose preference test, forced swimming immobility time and grip strength value, and the cardiac function of rats was evaluated by electrocardiogram and echocardiography. The levels of serum norepinephrine(NE), dopamine(DA) and 5-hydroxytryptamine(5-HT) were detected by enzyme-linked immunosorbent assay(ELISA), and biochemical detection was used to assess myocardial injury by measuring serum levels of high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglyceride(TG), total cholesterol(TC), aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH) and creatine kinase isoenzyme(CK-MB). Hematoxylin-eosin(HE) and Nissl staining were used to observe the pathological status of hippocampus and myocardial tissue in rats, the status of mitophagosomes in hippocampus and myocardium was observed by transmission electron microscope(TEM), and Western blot was used to detect the contents of Drp1, mitochondrial fusion protein 2(Mfn2), optic atrophy protein 1(OPA1), PINK1, Parkin, p62 and microtubule-associated protein light chain 3B(LC3B) in hippocampus and myocardium. ResultsCompared with the blank group, the food intake and water intake of rats in the model group decreased, the hair was dark yellow, the gloss and smoothness decreased, the spirit was depressed, the tongue was light purple or dark purple, accompanied by petechiae or ecchymosis, the sublingual collaterals were purple and black, and the tongue coating was white and smooth. The indexes of open field test, grip strength and sucrose preference of rats decreased significantly, and the immobility time of forced swimming increased significantly(P<0.01). Electrocardiogram and echocardiography showed that ST segment was significantly depressed, and left ventricular fractional shortening(LVFS) and left ventricular ejection fraction(LVEF) were significantly decreased(P<0.05, P<0.01). Pathological observation showed that the number of hippocampal neurons and myocardial cells decreased, and the structural damage was obvious. The levels of serum TC, TG, LDL-C, CK-MB, LDH, AST and ALT increased, while the levels of HDL-C, 5-HT, DA and NE decreased(P<0.05, P<0.01). TEM showed obvious mitochondrial damage in hippocampus and myocardial tissue. The protein expressions of Drp1, PINK1, Parkin and p62 in hippocampus and myocardium were increased, while the protein expressions of OPA1, Mfn2 and LC3BⅡ/Ⅰ were decreased(P<0.05, P<0.01). Compared with the model group, the mental state, body curling up, fear of cold and other symptoms of rats in each administration group were improved, and the degree of pale purple or dark purple tongue was reduced. The scores of open field test, grip strength, sucrose preference, LVFS and LVEF were increased, and the immobility time of forced swimming was shortened(P<0.05, P<0.01). The ST segment of electrocardiogram had a significant recovery(P<0.01), pathological observation showed that the damage of nerve cells and myocardial tissue was improved. The levels of serum TC, TG, LDL-C, CK-MB, LDH, AST and ALT decreased, while the levels of HDL-C, 5-HT, DA and NE increased(P<0.05, P<0.01). TEM showed that mitochondrial damage was reduced in hippocampal neurons and cardiomyocytes with visible mitochondrial autophagosomes. The protein expressions of Drp1, PINK1, Parkin and p62 in hippocampus and myocardium were decreased, while the protein expressions of OPA1, Mfn2 and LC3BⅡ/Ⅰ were increased(P<0.05, P<0.01). ConclusionBukan Yilidan can alleviate depression, lipid metabolism disorder and myocardial ischemia injury in rats with perimenopausal psycho-cardiac disease, and its mechanism may be related to inhibiting Drp1/PINK1/Parkin signaling pathway and enhancing mitochondrial autophagy.