Large-leaf yellow tea attenuates high glucose-induced vascular endothelial cell injury by up-regulating autophagy and down-regulating oxidative stress.

Vascular endothelial cell injury induced by high glucose (HG) plays an important role in the occurrence and development of diabetic vascular complications. Yellow tea has a protective effect on vascular endothelial cells. However, the molecular mechanisms underlying this effect are unclear. In this study, the effects of the n-butanol fraction of Huoshan large-leaf yellow tea extract (HLYTBE) on vascular endothelial injury were investigated using human umbilical vein endothelial cells (HUVECs) and diabetic mice. In HUVECs, HLYTBE significantly reduced the production of reactive oxygen species, increased the activity of anti-oxidases (superoxide dismutase and glutathione peroxidase), enhanced the production of reduced glutathione, and decreased the level of oxidized glutathione, thereby improving cell viability. HLYTBE also promoted autophagosome formation, increased the LC3-II/LC3-I ratio, increased the expressions of Beclin1 and Atg 5, and decreased the expression of p62. HLYTBE up-regulated p-AMPK and down regulated p-mTOR, and these effects were reversed by compound C, an AMPK inhibitor. HLYTBE reduced apoptosis and cytochrome C expression, and these effects were attenuated by the autophagy inhibitor 3-methyladenine. In vivo studies showed that HLYTBE improved the impaired pyruvate tolerance, glucose tolerance, and insulin resistance; reduced the concentrations of blood glucose, glycated serum protein, lipids, and 8-isomeric prostaglandin 2α; increased the anti-oxidase activity in serum; and alleviated pathological damage in the thoracic aorta of diabetic mice induced by high sucrose-high fat diet along with streptozotocin. The results suggest that HLYTBE protects the vascular endothelium by up-regulating autophagy via the AMPK/mTOR pathway and inhibiting oxidative stress.

[High preoperative pulmonary artery systolic pressure is associated with acute kidney injury and prognosis in patients underwent cardiopulmonary bypass surgery].

OBJECTIVE: To observe the relationship between pulmonary artery systolic pressure (PASP) and acute renal injury (AKI) and prognosis after cardiopulmonary bypass (CPB) heart surgery. METHODS: The clinical data of 9 860 patients who underwent CPB heart surgery in Beijing Anzhen Hospital from January 1st, 2015 to December 31st, 2016 were analyzed retrospectively. The patients were divided into two groups according to whether AKI occurred after operation. The clinical data were obtained from hospital information system (HIS) and DoCare including general information, types of operation, preoperative complication, ejection fraction, serum creatinine (SCr), PASP, intraoperative CPB duration, aortic occlusion duration, fluid balance, blood products and drug usage, postoperative mechanical ventilation duration, length of intensive care unit (ICU) and hospital stay, and perioperative central venous pressure (CVP). Multivariate Logistic regression analysis was used to screen the risk factors of AKI after operation. According to the preoperative PASP level, the patients were divided into ≥ 60 mmHg (1 mmHg = 0.133 kPa) group and < 60 mmHg group, and the incidence of AKI and prognosis after operation were compared between the two groups. All patients were followed up by telephone after discharge, and they were divided into survival group and death group according to the follow-up results, and the clinical data were compared between the two groups. Multivariate Cox regression analysis was used to screen the risk factors of long-term prognosis. Kaplan-Meier survival curve was used to analyze the long-term prognosis of two groups with different preoperative PASP levels. RESULTS: 6 285 patients were enrolled in the final analysis. (1) Among the 6 285 patients, 2 592 patients (41.2%) suffered from AKI after operation, of whom 1 697 (65.5%) were stage 1 according to Kidney Disease: Improving Global Outcomes (KDIGO), which was the main type of AKI. Univariate analysis showed that age, preoperative ejection fraction, SCr, PASP, coronary heart disease, hypertension, diabetes, intraoperative CPB duration, aortic occlusion duration, fluid balance, red blood cell input and norepinephrine, dopamine, epinephrine dosage, postoperative mechanical ventilation duration, the length of ICU and hospital stay, and perioperative CVP might be the risk factors of AKI after operation. Multivariate Logistic regression analysis showed that preoperative PASP was one of independent risk factors for AKI in patients undergoing CPB heart surgery [odds ratio (OR) = 4.753, 95% confidence interval (95%CI) was 1.328-8.417, P = 0.004]. The incidence of AKI after operation in PASP ≥ 60 mmHg group was significantly higher than that in < 60 mmHg group [73.8% (712/965) vs. 35.3% (1 880/5 320), P < 0.01]. (2) After a follow-up of (11±3) months, 237 patients (3.8%) died in 6 285 patients. The mortality of patients in PASP ≥ 60 mmHg group was significantly higher than that in < 60 mmHg group [9.5% (92/965) vs. 2.7% (145/5 320), P < 0.01]. Kaplan-Meier survival curve analysis showed that there was a significant difference between the two groups in cumulative survival rate (Log-Rank test: χ2 = 144.400, P < 0.001). Univariate analysis showed that male, age, preoperative hypertension, ejection fraction, PASP, intraoperative CPB duration, aortic occlusion duration, fluid balance, epinephrine dosage, postoperative mechanical ventilation duration, the length of ICU and hospital stay, and perioperative CVP might be risk factors for long-term death of patients undergoing CPB heart surgery. Multivariate Cox regression analysis showed that for every 1 mmHg increase in preoperative PASP, the long-term mortality increased by 1.126 times [hazard ratio (HR) = 1.126, 95%CI was 1.003-1.604, P = 0.021]. CONCLUSIONS: The increase of PASP is related to AKI after CPB heart surgery, which is an independent risk factor for long-term mortality.

MiR-183-5p protects rat hearts against myocardial ischemia/reperfusion injury through targeting VDAC1.

MicroRNAs have been reported to be implicated in myocardial ischemia/reperfusion (I/R) injury. The purpose of this study was to investigate the effect of miR-183-5p on I/R injury. Overexpression of miR-183-5p by agomiR transfection alleviated cardiac dysfunction and significantly reduced the infarct size in rats with myocardial I/R. MiR-183-5p also alleviated myocardial apoptosis with reduced apoptotic cells and lower levels of apoptosis associated proteins. in vitro experiments were conducted on rat H9c2 cells treated with anoxia/reoxygenation (A/R). Annexin V/propidium iodide (PI) staining and flow cytometry reported that the ratio of apoptotic cells decreased by miR-183-5p transfection before A/R treatment. Moreover, according to binding sequence prediction and Dual luciferase reporter assay, we explored that voltage-dependent anion channel 1 (VDAC1), which aggravates myocardial injury and apoptosis reported in our former research, was a target of miR-183-5p. In conclusion, miR-183-5p can efficiently attenuate I/R injury and miR-183-5p may exert its effect through repressing VDAC1 expression.

Regulation of VDAC1 contributes to the cardioprotective effects of penehyclidine hydrochloride during myocardial ischemia/reperfusion.

Penehyclidine hydrochloride (PHC) preconditioning can alleviate myocardial ischemia/reperfusion (I/R) injury and inhibits the upregulation of voltage-dependent anion channel 1 (VDAC1) during I/R. To validate that VDAC1 is a bona fide target of PHC for the protection against myocardial I/R injury, VDAC1 expression construct was delivered by lentiviruses into rat left ventricular myocardium before PHC preconditioning and myocardial I/R. Overexpression of VDAC1 exacerbated cardiac dysfunction and myocardial injury following I/R, and abolished the cardioprotective effect of PHC during I/R injury. Moreover, VDAC1 overexpression with myocardial I/R further increased cytochrome c release from mitochondria to cytoplasm, elevated the levels of cleaved caspase-3 and Bax, and decreased the level of Bcl-2 as compared with I/R alone, and PHC-mediated inhibition of mitochondria-dependent apoptosis during myocardial I/R was abolished by VDAC1 overexpression. In addition, VDAC1 was overexpressed in H9c2 cardiomyocytes undergoing anoxia/reoxygenation (A/R) with or without PHC pretreatment. The in vitro results showed that overexpression of VDAC1 further reduced mitochondrial membrane potential, increased mitochondrial membrane permeability and enhanced mitochondria-dependent apoptosis in H9c2 cells after A/R, and VDAC1 overexpression abrogated the protective effect of PHC on the mitochondrial function and integrity during A/R. In conclusion, exogenous overexpression of VDAC1 during myocardial I/R inhibits the cardioprotective effects of PHC. These effects may be associated with the suppression of VDAC1 expression.

Combination of berberine and evodiamine inhibits intestinal cholesterol absorption in high fat diet induced hyperlipidemic rats.

BACKGROUND: Hyperlipidemia characterized of elevated serum lipid levels is a prevalent disease frequently resulting in cardiovascular disease (CVD). Berberine and evodiamine are herbal products of traditional Chinese herb Coptis chinensis and Evodia rutaecarpa, which are indicated to exert regulation of lipid metabolism. Therefore, the objective of this study was to investigate the lipid-lowering effect of berberine and evodiamine combination in hyperlipidemic rats. METHOD: The rat model of hyperlipidemia was established by providing high-fat-diet (HFD) for 4 weeks. Berberine (BB), evodiamine (EV), and their combination (BB + EV) were orally administered to HFD induced rats for 4 weeks. Body weight, food utilization, histopathology of liver tissues, lipid profiles of serum and liver were measured. Gas chromatography (GC) analysis was applied to examine the level of plasma total cholesterol and ß- Sitosterol (BS) to estimate cholesterol absorption activity. Furthermore, intestinal NPC1L1, ACAT2, and ApoB48 protein expressions were evaluated by immunohistochemical assay. RESULT: According to the results, decreased levels of serum cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), as well as hepatic TC were showed in hyperlipidemic rats treated by combination of berberine and evodiamine. GC analysis indicated that the elevated plasma BS was significantly ameliorated by BB, EV, and BB + EV. In addition, immunohistochemical analysis revealed that BB + EV treatment down-regulated the expressions of intestinal NPC1L1 and ACAT2, and ApoB48 in HFD induced rats. CONCLUSION: Based on the above results, combination of berberine and evodiamine exerted a promising preventive effect on hyperlipidemia, partially through inhibiting intestinal absorption of cholesterol.