The traditional Chinese medicine formula Fufang-Zhenzhu-Tiaozhi protects myocardia from injury in diabetic minipigs with coronary heart disease

Song, Lixia; Zhang, Dongxing; Guo, Caijuan; Gu, Zhanhui; Wang, Lexun; Yao, Yu Si; Wang, Hong; Zeng, Zhihuan; Wang, Weixuan; Yang, Yiqi; Bei, Weijian; Rong, Xianglu; Guo, Jiao

doi:10.1016/j.biopha.2021.111343

Cited by 21 publications

(28 citation statements)

References 28 publications

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“…The preparation of FTZ extract was consistent with the protocol described previously [24]. Animals 20-22 weeks old castrated male Chinese Wuzhishan minipigs were purchased from Guangdong Laboratory Animals Monitoring Institute (Certi cation: SYXK Guangdong 2017-0125, Guangzhou, China).…”

Section: Preparation Of Ftzmentioning

confidence: 99%

“…After 4 weeks of ND or HFSCD feeding, the coronary artery disease minipigs were induced by balloon injury, and the detailed protocol of surgery was described previously [24].…”

Section: Preparation Of Ftzmentioning

confidence: 99%

“…After the surgery, the DM pigs were randomly allocated into three groups: model group (Mod, n = 4), FTZ group (FTZ, n = 5), and positive control drug group (Metformin + Atorvastatin, M+A, n = 5). FTZ (1.2 g/kg) was given with meals in the FTZ group daily [24]. Metformin (57.08 mg/kg/d, according to the daily dose of Metformin in the clinical treatment of 2.550 g/60kg) and Atorvastatin (0.92 mg/kg/d, according to the daily dose in the clinical treatment of 40 mg/60kg) were given with meals in M+A group.…”

Section: Animal Treatmentmentioning

confidence: 99%

“…The animals were anesthetized with Zoletil 50 injection(Virbac,Nice France), which contains tiletamine, a separate anesthetic component, and zolazepam (with the effects of both sedative and muscle relaxation) 5 mg/kg intravenously. The analysis of imaging results of left anterior descending branch (LAD) was described as previously with CGO-2100 (Digital Subtraction Angiography system, Wandong Medical, Peking, China) [24]. The measurement indicators include: (1) the length of two different angles of the target vessel; (2) the sum of the proximal diameter and distal diameter of the lesion as the reference vascular diameter; (3) minimal lumen diameter rate (MLD%) = (1 -actual diameter/reference diameter) × 100% (the average sum of the diameter stenosis rates of two different angles); (4) minimum lumen area rate (MLA%) = (1 -actual stenosis area/reference area) × 100% (the average sum of the area narrow rates of two different angles) [25].…”

Section: Angiographymentioning

confidence: 99%

“…Previous studies have shown that FTZ could inhibit the development of atherosclerosis in the atherosclerosis model and exhibit the cardioprotective effect in the diabetic minipig model with coronary heart disease (DM-CHD) [21][22][23][24]. However, the effect and molecular mechanisms underlying FTZ in DM-CHD are not clear.…”

Section: Introductionmentioning

confidence: 99%

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Atherosclearosis plaque formation is related to EndMT in diabetic minipigs with coronary heart disease and the effect of Traditional Chinese medicine FTZ Prescription

Wang

Zhang

Zhan

et al. 2021

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Background: Coronary heart disease (CHD) caused by diabetes mellitus (DM) is the main cause of death in diabetic patients. The treatment of diabetes complicated with coronary heart disease (DM-CHD) is still a big challenge in the medical practice. Endothelial-mesenchymal transition (EndMT) has been considered as the key process in endothelial dysfunction in the atherosclerotic diseases, including DM-CHD. The traditional Chinese prescription Fufang Zhenzhu Tiaozhi (FTZ) formula is used to treat diabetes and dyslipidemia. Recently, several studies have shown the therapeutic effect of FTZ in cardiovascular diseases. However, the mechanism of the protection on coronary atherosclerosis is still needed for further investigation.Objective: To evaluate the efficacy of FTZ in preventing DM-CHD and explore the specific mechanism of FTZ based on EndMT. Methods: DM-CHD minipigs model constructed by using high-fat/high-sucrose/high-cholesterol diet (HSFCD) combined with streptozotocin (STZ) and coronary balloon injury, then randomly divided into control (Ctrl), DM-CHD model (Mod), DM-CHD treated with FTZ (FTZ) or positive drug (metformin and atorvastatin, M+A). Twenty-two weeks after administration, the cardiac functions of pigs were detected by ultrasound and electrocardiography (ECG). The stenosis and plaque of the left anterior descending (LAD) coronary artery were assessed through angiography, intravascular ultrasound (IVUS), and optical coherence tomography (OCT). Pigs were sacrificed after all examinations and the tissues were collected for further testing. The serum levels of blood glucose and lipid, myocardial injury markers, and inflammatory factors were detected. The biomarkers of EndMT were observed. The potential targets and signaling pathways were analyzed. The human umbilical vein endothelial cell (HUVEC) was cultured for testing the effect of FTZ under high glucose (HG).Results: In the Mod group, the serum levels of FBG, TC, TG, HDL-C, and LDL-C and the myocardial injury markers (LDH, cTnT, CK-MB) were increased significantly. The ST segment and the height of the T wave of ECG were significantly elevated in the Mod group. The results of coronary angiography, OCT, and IVUS showed that there was an obvious narrow in the coronary artery of the Mod group, and the pathological changes were mainly intimal fibrosis. Furthermore, the levels of TGF-β1 and α-SMA significantly increased while the levels of CD31 and VE- cadherin notably decreased in the Mod group, which showed EndMT characteristic. Besides, the inflammation and apoptosis pathways were markedly activated in the Mod group. After treatment with FTZ, the glucolipid metabolism and the myocardium injury were effectively improved in DM-CHD minipigs. FTZ treatment improved the function of the heart and alleviated coronary stenosis. The expression of α-SMA in the coronary artery was significantly decreased, and the expression of CD31 and VE-cadherin were increased in the coronary artery of the FTZ group minipigs. In addition, FTZ treatement inhibited the expressions of the inflammatory relative protein p-IκB/p-NF-κB/IL-1β and the apoptosis proteins Bax/cleave-Caspase-3 in the coronary artery tissue. Additionally, FTZ ameliorated the injury effect and high migration activity of HUVECs caused by HG. Conclusions: Coronary atherosclearosis plaque formation is related to EndMT and FTZ protect heart partly via inhibiting coronary endothelial EndMT and regulating inflammation in DM-CHD pigs.

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Section: Preparation Of Ftzmentioning

confidence: 99%

“…After 4 weeks of ND or HFSCD feeding, the coronary artery disease minipigs were induced by balloon injury, and the detailed protocol of surgery was described previously [24].…”

Section: Preparation Of Ftzmentioning

confidence: 99%

Section: Animal Treatmentmentioning

confidence: 99%

Section: Angiographymentioning

confidence: 99%