[Berberine alleviates programmed necrosis of metabolic-associated fatty liver disease via activating Nrf2 pathway in mice].

Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1ß levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1ß levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.

[Effects of epicardial adipose tissue and inflammatory factors on left ventricular diastolic function in patients with coronary heart disease].

Objective: To investigate the effects ofepicardial adipose tissue volume (EATV) and inflammatory factors on left ventricular diastolic function in patients with coronary heart disease(CHD). Methods: The clinical data of patients with coronary heart disease receiving coronary artery intervention therapy from January 2014 to October 2015 in TEDA international cardiovascular hospital were preoperatively collected.We measured the indexes of EATV and left ventricular diastolic function. Results: The difference of age (F=7.76, P=0.01), IL-6 (F=14.34, P<0.01), Hs-CRP (F=4.08, P=0.04), adiponect-in (F=4.50, P=0.04) and EATV (F=71.29, P<0.01) between the diastolicdysfunction group (n=156) and the normal group (n=76) was statistically significant.Multivariate logistic regression analysis showed that EATV was a risk factor for left ventricular diastolic dysfunction in patients with coronary artery disease (P<0.05), OR=1.05, 95%CI (1.03-1.06). The AUC value of EATV in the diagnosis of left ventriculardiastolic function in patients with coronary heart disease was 0.79, 95%CI (0.73-0.85) P<0.01. Conclusions: EATV can be used as an independent risk factor for left ventricular diastolic dysfunction.It has some non-invasive diagnosis and predictive value, and it can be used as a new therapeutic target.