Similarities and differences of myocardial metabolic characteristics between HFpEF and HFrEF mice based on LC-MS/MS metabolomics / 中华心血管病杂志

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.

Effects of hyperbaric oxygen on the level of brain derived neurotrophic factor and parvalbumin in hippocampal CA1 region of valproic acid autism rats / 中华实用儿科临床杂志

Objective To explore the outcome of brain derived neurotrophic factor(BDNF) and parvalbumin (PV) positive neurons after hyperbaric oxygen intervention for the valproic acid(VPA) autism rats in hippocampal CA1 region.Methods The animal model of autism was established by the methods of Schneider and Przewlocki.Animal model groups of autism were obtained in male offspring of the Wistar rats that received intraperitoneal injection of 600 mg/kg VPA on the 12.5 day after pregnancy according to the eye opening time,behavior,weaning weight and the learning and memory abilities which were evaluated by the Y electricity maze test on the 28th day after birth.Forty-eight male VPA autism rats were randomly divided into high-pressure high-oxygen group,high-pressure air group and normal pressure high-oxygen group and normal pressure air group(n =12,each group).Normal control group was obtained in male offspring of Wistar rats that received intraperitoneal injection of equivalent physiological saline in the same period (n =12).Using the immunohistochemistry methods and image analysis to examine the number of BDNF and PV positive neurons in hippocampal CA1 region of different groups.Results The number of BDNF positive neurons in normal pressure air model group was more than that in the normal pressure air control group,with statistical difference between them(5.00 ± 1.60 vs 3.00 ± 1.04,t =3.633,P =0.001).The number of the PV positive neurons in the normal pressure air model group was more than that of the normal pressure air control group,with statistical difference between them (5.33 ± 0.99 vs 2.83 ± 1.29,t =5.369,P =0.000).The number of the PV positive neurons in the high-pressure high-oxygen group was less than that in the normal pressure air model group,with statistical difference between them (3.33 ±0.99 vs 5.33 0.99,t =4.975,P =0.000).The number of the PV positive neurons in the high-pressure highoxygen group was less than that in the high-pressure-air model group (3.33 ± 0.99 vs 4.67 ± 1.92,t =-2.138,P =0.044).Conclusions The pathogenesis of autism may be related to the expression level of BDNF and PV in the hippocampal CA1 region and this may serve as the mechanism of hyperbaric oxygen intervention of autism animal model for effective treatment.