Effect of sheep bone protein hydrolysate on promoting calcium absorption and enhancing bone quality in low-calcium diet fed rats.

Calcium deficiency is prone to fractures, osteoporosis and other symptoms. In this study, sheep bone protein hydrolysates (SBPHs) were obtained by protease hydrolysis. A low-calcium-diet-induced calcium-deficiency rat model was established to investigate the effects of SBPHs on calcium absorption and intestinal flora composition. The results showed that an SBPHs + CaCl2 treatment significantly increased the bone calcium content, bone mineral density, trabecular bone volume, and trabecular thickness, and reduced trabecular separation, and changed the level of bone turnover markers (P < 0.05). Supplementation of SBPHs + CaCl2 can remarkably enhance the bone mechanical strength, and the microstructure of bone was improved, and the trabecular network was more continuous, complete, and thicker. Additionally, SBPHs + CaCl2 dietary increased the abundance of Firmicutes and reduced the abundance of Proteobacteria and Verrucomicrobiota, and promoted the production of short chain fatty acids. This study indicated that SBPHs promoted calcium absorption and could be applied to alleviate osteoporosis.

Effects of exercise on muscle fiber conversion, muscle development and meat quality of Sunit sheep.

This study aimed to investigate the effects of exercise on muscle fiber conversion, muscle development and meat quality in the biceps femoris (BF) muscle of Sunit sheep. Twelve Sunit sheep with similar body weight were divided into two groups: control group (C group) and exercise group (E group), E group lambs underwent 6 km of exercise training per day for 90 d. The findings revealed that compared with the C group, exercise training enhanced the expression of MyHC IIa mRNA, decreased the number ratio of type IIB muscle fibers and the expression of MyHC IIb mRNA (P < 0.05). Furthermore, the E group lamb displayed higher creatine kinase (CK) activity, and lactic acid levels (P < 0.05), while glycogen content and lactic dehydrogenase (LDH) activity showed opposite trends (P < 0.05). Exercise significantly up-regulated the mRNA expression of AMP-activated protein kinase α1 (AMPKα1), sirtuin1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), cytochrome c oxidase IV (COX IV), protein kinase B (Akt), mammalian target of rapamycin (mTOR) and p70 Ribosomal S6 Kinase 1 (p70s6k1) (P < 0.05), suggesting exercise promoted muscle fiber conversion by mediating AMPK/PGC-1α pathway, and improved skeletal muscle development via Akt/mTOR pathway. Besides, backfat thickness and pH45min value in the E group decreased significantly, while the pH24, a*, and shear force value increased significantly (P < 0.05). To conclude, this study suggested that exercise training can be used to alter muscle fiber characteristics and muscle development in lamb production.

Effect of dietary arginine supplementation on protein synthesis, meat quality and flavor in growing lambs.

This study aimed to assess the effect of dietary arginine supplementation on protein synthesis, meat quality and flavor in lambs. Eighteen Dorper (♂) × Small Tailed Han sheep (♀) crossed ewe lambs of similar weight (27.29 ± 2.02 kg; aged 3 months) were assigned to two groups, the control group was fed the basal diet (Con group), and the arginine group (Arg group) was supplemented with 1% l-arginine based on the Con group for 90 d. The results suggested that dietary arginine significantly increased final body weight, loin eye muscle area, muscle fiber diameter, cross-sectional area (P < 0.050), and decreased shear force value and cooking loss (P < 0.050), as well as altered the composition and contents of volatile flavor compounds in lambs. Importantly, the total protein (TP) content, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) activities in serum, branched-chain aminotransferase (BCAT), AST, ALT activities and neuronal nitric oxide synthase (nNOS) gene expression and content were elevated (P < 0.050), while content of urea nitrogen (BUN) in serum and 3-methylhistidine (3-MH) were decreased in arginine fed lambs (P < 0.050). In addition, arginine triggered muscle protein synthesis through protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, while minimized protein degradation by regulating gene expression of myogenin (MyoG), myostatin (MSTN), muscle atrophy F-box (MAFbx) and forkhead box O3 family (FoxO3) (P < 0.050). Taken together, this study suggested that arginine can be used to improve protein deposition and meat quality in lamb production.

Supplemental Clostridium butyricum modulates skeletal muscle development and meat quality by shaping the gut microbiota of lambs.

This study evaluated the contributions of Clostridium butyricum on skeletal muscle development, gastrointestinal flora and meat quality of lambs. Eighteen Dorper (♂) × Small Tailed Han sheep (♀) crossed ewe lambs of similar weight (27.43 ± 1.94 kg; age, 88 ± 5 days) were divided into two dietary treatments. The control group was fed the basal diet (C group), and the probiotic group was supplemented with C. butyricum on the basis of the C group (2.5 × 108 cfu/g, 5 g/day/lamb; P group) for 90 d. The results showed that dietary C. butyricum elevated growth performance, muscle mass, muscle fiber diameter and cross-sectional area, and decreased the shear force value of meat (P < 0.05). Moreover, C. butyricum supplementation accelerated protein synthesis by regulating the gene expression of IGF-1/Akt/mTOR pathway. We identified 54 differentially expressed proteins that regulated skeletal muscle development through different mechanisms by quantitative proteomics. These proteins were associated with ubiquitin-protease, apoptosis, muscle structure, energy metabolism, heat shock, and oxidative stress. The metagenomics sequencing results showed that Petrimonas at the genus level and Prevotella brevis at the species level in the rumen, while Lachnoclostridium, Alloprevotella and Prevotella at the genus level in the feces, were significantly enriched in the P group. Also, butyric acid and valeric acid levels were elevated in both rumen and feces of the P group. Overall, our results support the idea that C. butyricum could change gastrointestinal flora, and affect skeletal muscle development and meat quality of lambs by modulating gut-muscle axis.

Effects of ultrasound on the structural and functional properties of sheep bone collagen.

The study evaluated the effect of an ultrasound-assisted treatment on the structural and functional properties of sheep bone collagen (SBC). The type and distribution of SBC were analyzed by proteome (shotgun) technology combined with liquid chromatography-tandem mass spectrometry. Compared with pepsin extraction, the ultrasound-assisted treatment significantly increased the collagen extraction rate by 17.4 pp (P < 0.05). The characteristic functional groups and structural integrity of collagen extracted by both methods were determined via Fourier transform infrared spectroscopy, ultraviolet absorption spectroscopy, and fluorescence spectroscopy. Circular dichroism spectra revealed that the ultrasound-assisted pretreatment reduced α-helix content by 1.6 pp, ß-sheet content by 21.9 pp, and random coils content by 28.4 pp, whereas it increased ß-turn content by 51.9 pp (P < 0.05), compared with pepsin extraction. Moreover, ultrasound-assisted treatment collagen had superior functional properties (e.g., solubility, water absorption, and oil absorption capacity) and foaming and emulsion properties, compared with pepsin extraction. Furthermore, the relative content of type I collagen in ultrasound-assisted extracted SBC was highest at 79.66%; only small proportions of type II, VI, X, and XI collagen were present. Peptide activity analysis showed that SBC had potential antioxidant activity, dipeptidyl peptidase 4 inhibitory activity, and angiotensin-converting enzyme inhibitory activity; it also had anticancer, antihypertensive, anti-inflammatory, and immunomodulatory effects.

Dietary linseed supplementation improves meat quality and flavor of sheep by altering muscle fiber characteristics and antioxidant capacity.

Linseed as a common oil crop that has been implicated in regulating the meat quality of animals. The aim of this investigation was to establish the effects of dietary linseed supplementation on carcass traits, meat quality, muscle fiber characteristics, volatile compounds and antioxidant capacity of sheep. Twenty-four Sunit sheep were distributed into 2 groups with different diet: control (CO) fed a standard diet and linseed (LS, 8% of extruded linseed). The results showed that linseed not only increased M. longissimus thoracis (LT) increased the loin-eye area but also decreased pH24h, L* and shear force. Meanwhile, linseed increased mRNA expression of MyHCI and MyHCIIx and decreased in cross-sectional area (CSA) and muscle fiber diameter. In addition, linseed altered the composition of meat volatile flavor compounds, such as Z-10-Pentadecen-1-ol, pentanal, 2-Octenal, (E)-, decanal, butane, and 2-heptanone. Moreover, linseed increased total antioxidative capacity (T-AOC) activity, the mRNA expression of glutathione peroxidase (GSH-Px) and catalase (CAT), decreased malondialdehyde (MDA) content. Overall, the results suggest that linseed is an effective feed additive in improving meat quality and flavor. The underlying mechanisms for its effectiveness may be partly due to a change in muscle fiber characteristics and antioxidant capacity.

Effect of Feeding System on Muscle Fiber Composition, Antioxidant Capacity, and Nutritional and Organoleptic Traits of Goat Meat.

The objective of this study was to evaluate the effect of feeding system on muscle fiber composition, antioxidant capacity, and nutritional and organoleptic traits of goat meat. Goats that grazed on flatland (whole area with about 0% inclination, FG group) and mountain range (whole area with about 40% inclination, MG group) were selected for the analysis. The results showed that grazing on flatland increased oxidized-twitch fiber percentage, the expression of the MyHC IIa gene (p < 0.001), the activity of glutathione peroxidase (GSH-Px) (p < 0.05), total antioxidant capacity (T-AOC) (p = 0.001), and radical scavenging ability (RSA) (p < 0.05); meanwhile, the MyHC IIb gene expression (p < 0.01) and malondialdehyde (MDA) content (p = 0.001) were decreased. Feeding system affected nutritional and organoleptic traits of goat meat, and grazing on flatland increased protein content, total content of monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), pH45min, a* value, and variety of volatile flavor compounds but decreased the content of saturated fatty acid (SFA), shear force, and b* value. In addition, the key flavor substances were screened using relative odor activity value (ROAV), including hexanal, heptanal, (E)-2-octenal, octanal, nonanal, decanal, (E)-2-nonenal, and 1-octen-3-ol. Among them, 1-octen-3-ol and (E)-2-nonenal were the most contributing flavor compounds in the FG and MG groups, respectively, providing distinctive odor to goat meat.

Lipid transformation during postmortem chilled aging in Mongolian sheep using lipidomics.

This present study aimed to investigate the effects of postmortem chilled aging on lipid and molecular transformation mechanisms in Mongolian sheep. UPLC-ESI-MS/MS was used to identify 812 lipids in Mongolian sheep within four days of chilled aging. Using multivariate analysis, 95 significant differential lipids were identified. The levels of phosphatidylcholine, phosphatidylinositol, and certain free fatty acids were observed to rise significantly, while other phospholipids and acylcarnitines showed a downward trend. In addition, levels of most of the lysophospholipids increased significantly in the early postmortem period; however, their levels did not alter significantly after 48 h. The Kyoto encyclopedia of genes and genomes pathway analysis revealed that these differential lipids are primarily involved in glycerophospholipid metabolism, linoleic acid metabolism, arachidonic acid metabolism, and thermogenesis. Our results have important implications in terms of understanding lipid transformation and changes in meat quality during postmortem chilled aging in Mongolian sheep.

Effects of Feeding Regimes and Postmortem Aging on Meat Quality, Fatty Acid Composition, and Volatile Flavor of Longissimus Thoracis Muscle in Sunit Sheep.

The effects of different feeding regimes on antioxidant activity, meat quality, fatty acid composition, lipid oxidation, and volatile matter production in the longissimus thoracis (LT) of Sunit sheep at 0, 24, 48, 72, and 96 h postmortem were investigated. The results showed that the activity of antioxidant enzymes, tenderness, water retention, and percentage of unsaturated fatty acids were significantly higher in the pasture-fed sheep (PF) than in the concentrate-fed sheep (CF) (p < 0.05). During postmortem aging, antioxidant activity, water retention, and the proportion of unsaturated fatty acids decreased in the PF and CF (p < 0.05), while malondialdehyde (MDA) content, the proportion of saturated fatty acids, and the content of flavor substances resulting from fat oxidation increased. After 24 h of LT muscle aging, the pH and shear force of the meat started to increase and the color stabilized. The differences between shear force values and lipid volatile flavor substance content of sheep meat under different feeding regimes disappeared with increasing aging time. PF had better oxidative stability and fatty acid composition. Postmortem aging changed the oxidative stability of sheep meat, thus affecting meat quality and fatty acid composition and consequently meat flavor composition, while aging also eliminated to some extent the differences caused by feeding regimes.

Weft-Knitted Spacer Fabric for Highly Stretchable-Compressible Strain Sensor, Supercapacitor, and Joule Heater.

The development of wearable electronic devices has greatly stimulated the research interest of textile-based strain sensors, which can effectively combine functionality with wearability. In this work, the fabrication of highly stretchable and compressible strain sensors from weft-knitted spacer fabric was reported. Carbon nanotubes and polypyrrole were deposited on the surface of fabric via an in situ polymerization approach to reduce the electrical resistance. The as-fabricated WSP-CNT-PPy strain sensor exhibits high electrical conductivity and stable strain-sensing performance under different stretching deformations. The WSP-CNT-PPy strain sensor can be stretched up to 450% and compressed to 60% with a pressure of less than 50 KPa, which can be attributed to the unique loop and interval filament structures. The distinguishing response efficiency of WSP-CNT-PPy can effectively detect faint and strenuous body movements. In addition, the electrochemical behavior of WSP-CNT-PPy was also characterized to study the comprehensive properties. The electro-heating performance was also evaluated for feasible Joule heater applications. This work demonstrates the practicability of WSP-CNT-PPy strain sensor fabric for real-time monitoring in promising wearable garments.

Isolation, Purification and Structure Identification of a Calcium-Binding Peptide from Sheep Bone Protein Hydrolysate.

To isolate a novel peptide with calcium-binding capacity, sheep bone protein was hydrolyzed sequentially using a dual-enzyme system (alcalase treatment following neutrase treatment) and investigated for its characteristics, separation, purification, and structure. The sheep bone protein hydrolysate (SBPH) was enriched in key amino acids such as Gly, Arg, Pro, Leu, Lys, Glu, Val, and Asp. The fluorescence spectra, circular dichroism spectra, and Fourier-transform infrared spectroscopy results showed that adding calcium ions decreased the α-helix and ß-sheet content but significantly increased the random and ß-turn content (p < 0.05). Carboxyl oxygen and amino nitrogen atoms of SBPH may participate in peptide−calcium binding. Scanning electron microscopy and energy dispersive spectrometry results showed that SBPH had strong calcium-chelating ability and that the peptide−calcium complex (SBPH−Ca) combined with calcium to form a spherical cluster structure. SBPH was separated and purified gradually by ultrafiltration, gel filtration chromatography, and reversed-phase high-performance liquid chromatography. Liquid chromatography-electrospray ionization/mass spectrometry identified the amino acid sequences as GPSGLPGERG (925.46 Da) and GAPGKDGVRG (912.48 Da), with calcium-binding capacities of 89.76 ± 0.19% and 88.26 ± 0.25%, respectively. The results of this study provide a scientific basis for the preparation of a new type of calcium supplement and high-value utilization of sheep bone.

Effect of dietary probiotics supplementation on meat quality, volatile flavor compounds, muscle fiber characteristics, and antioxidant capacity in lambs.

This study investigated the effects of probiotics on growth performance, meat quality, muscle fiber characteristics, volatile compounds, and antioxidant capacity in lambs. A total of 24 Sunit lambs were randomly allocated into two groups, each consisting of three replicates of four lambs. Throughout the experiment period, the lambs were fed with based diet (CON) and 10 g probiotics/d supplemented diet (PRO). Compared with the CON group, the number of lactic acid bacteria in fecal samples of PRO group was significantly increased (p < .05) and the coliforms were significantly decreased (p < .05). Dietary probiotics supplementation decreased pH24h, L*, and shear force (p < .05). The muscle fibers were switched from type IIB to type I, with a decrease in the mean cross-sectional area (CSA) (p < .05) of longissimus thoracis (LT) muscle. Also, probiotics altered the composition of meat volatile flavor compounds, such as nonanal, undecanal, 1-pentanol, 1-hexanol, and 2,3-octanedione. In addition, probiotics increased the total antioxidative capacity (T-AOC) and catalase (CAT) activity of LT muscle, while it decreased superoxide dismutase (SOD) activity (p < .05). Overall, these results indicated that probiotics could be used as an effective feed additive by improving meat tenderness and flavor.

Effects of oxidative stability variation on lamb meat quality and flavor during postmortem aging.

This study evaluated the effects of oxidative stability variation on meat quality and flavor in biceps femoris (BF) and longissimus dorsi (LD) muscles of lambs during postmortem aging. The samples were stored at 4±1℃; the meat quality, flavor and muscle oxidative stability were measured on day 0, 1, 2, 3, and 4 of postmortem aging. The results showed that malondialdehyde (MDA) content increased in both muscle types; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities decreased, as did total antioxidative capacity (T-AOC). LD muscle showed lower MDA content and antioxidative activity than BF muscle. Meat quality analyses indicated that aging increased the lightness (L*), redness (a*), and yellowness (b*) values of meat while improving its tenderness. Gas chromatography-mass spectrometry results showed that volatile flavor compounds were more abundant in LD muscle than in BF muscle. As the aging time extended, relative contents of aldehyde and alcohol increased in both muscles. The key flavor compounds during postmortem aging including heptanal, octanal, nonanal, and decanal were screened by relative odor activity value (ROAV), and the content of key flavor compounds showed the trend of increasing, which were usually associated with fresh green grass, nutty, and fat descriptors. In conclusion, the oxidative muscles displayed better antioxidative capacity, and postmortem aging altered the oxidative stability of lamb muscle, which affected the meat quality and flavor. PRACTICAL APPLICATION: Meat aging is an important strategy to improve the quality of various meat traits (including flavor). The results of this work could be of interest to meat professionals who will be able to apply in actual production by choosing the best aging time based on flavor and meat quality for different muscle parts.

Public transcriptome database-based selection and validation of reliable reference genes for breast cancer research.

BACKGROUND: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is the most sensitive technique for evaluating gene expression levels. Choosing appropriate reference genes (RGs) is critical for normalizing and evaluating changes in the expression of target genes. However, uniform and reliable RGs for breast cancer research have not been identified, limiting the value of target gene expression studies. Here, we aimed to identify reliable and accurate RGs for breast cancer tissues and cell lines using the RNA-seq dataset. METHODS: First, we compiled the transcriptome profiling data from the TCGA database involving 1217 samples to identify novel RGs. Next, ten genes with relatively stable expression levels were chosen as novel candidate RGs, together with six conventional RGs. To determine and validate the optimal RGs we performed qRT-PCR experiments on 87 samples from 11 types of surgically excised breast tumor specimens (n = 66) and seven breast cancer cell lines (n = 21). Five publicly available algorithms (geNorm, NormFinder, ΔCt method, BestKeeper, and ComprFinder) were used to assess the expression stability of each RG across all breast cancer tissues and cell lines. RESULTS: Our results show that RG combinations SF1 + TRA2B + THRAP3 and THRAP3 + RHOA + QRICH1 showed stable expression in breast cancer tissues and cell lines, respectively, and that they displayed good interchangeability. We propose that these combinations are optimal triplet RGs for breast cancer research. CONCLUSIONS: In summary, we identified novel and reliable RG combinations for breast cancer research based on a public RNA-seq dataset. Our results lay a solid foundation for the accurate normalization of qRT-PCR results across different breast cancer tissues and cells.

Neochlorogenic acid: an anti-HIV active compound identified by screening of Cortex Mori [Morus Alba L. (Moraceae)].

CONTEXT: Chinese herbs such as Cortex Mori [Morus alba L. (Moraceae)] may inhibit human immunodeficiency virus (HIV), but active compounds are unknown. OBJECTIVE: Screening of Cortex Mori and other herbs for anti-HIV active compounds. MATERIALS AND METHODS: HIV-1 virus (multiplicity of infection: 20), and herbs (dissolved in dimethyl sulfoxide, working concentrations: 10, 1, and 0.1 mg/mL) such as Cortex Mori, etc., were added to 786-O cells (105 cell/well). Zidovudine was used as a positive control. Cell survival and viral inhibition rates were measured. The herb that was the closest inactivity to zidovudine was screened. Mass spectrometry identified the active compounds in herbs (mobile phase: 0.05% formic acid aqueous solution and acetonitrile, gradient elution, detection wavelength: 210 nm). The effect of the compounds on reverse transcriptase (RT) products were evaluated by real-time PCR. Gene enrichment was used to analyse underlying mechanisms. RESULTS: With a dose of 1 mg/mL of Cortex Mori, the cell survival rate (57.94%) and viral inhibition rate (74.95%) were closest to the effect of zidovudine (87.87%, 79.81%, respectively). Neochlorogenic acid, one of the active ingredients, was identified by mass spectrometry in Cortex Mori. PCR discovery total RT products of neochlorogenic acid group (mean relative gene expression: 6.01) significantly inhibited (control: 35.42, p < 0.0001). Enrichment analysis showed that neochlorogenic acid may act on haemopoietic cell kinase, epidermal growth factor receptor, sarcoma, etc., thus inhibiting HIV-1 infection. CONCLUSIONS: For people of low socioeconomic status affected by HIV, Chinese medicine (such as Cortex Mori) has many advantages: it is inexpensive and does not easily produce resistance. Drugs based on active ingredients may be developed and could have important value.

The endocrine disruptor hexachlorobenzene can cause oxidative damage in the testis of mice.

Hexachlorobenzene is a widespread endocrine disruptor. However, the effect of hexachlorobenzene on the reproductive toxicity of male animals is not described in detail. To investigate the toxic effects of hexachlorobenzene in mouse testes, hexachlorobenzene (100, 400 and 1,600 mg/kg) is fed to mice. The morphology of the testes was analysed by haematoxylin and eosin staining. We also investigated the expression of biomarkers for oxidative stress. Database screening identified proteins that interact with hexachlorobenzene and the aryl hydrocarbon receptor, a weak ligand of hexachlorobenzene. Gene enrichment analysis and protein-protein interaction analyses were also performed. Real-time PCR detected the expression levels of the aryl hydrocarbon receptor in four different stages of testicular cells. We identified significantly increased activity levels of superoxide dismutase (p < 0.05) and catalase (p < 0.05) in mouse testes that had been subjected to oxidative damage. The cell thickness and the number of cell layers in the seminiferous tubules had decreased by varying degrees after the hexachlorobenzene treatment. Particularly, cytokines and proteins involved in transcriptional regulation showed enrichment. The highest levels of aryl hydrocarbon receptor expression were detected in the spermatocytic cell line. Hexachlorobenzene exposure caused testicular damage in mice. The toxicity characteristics of hexachlorobenzene were not dose-dependent.

Therapeutic effects of Sheng Xue Fang in a cyclophosphamide-induced anaemia mouse model.

CONTEXT: Sheng Xue Fang (SXF) has been used to treat anaemia for decades with good efficacy. OBJECTIVE: To study the effect and possible mechanism of SXF to restore haematopoietic function. MATERIALS AND METHODS: Balb/c mice (10 per/group, half male, half female) were treated with SXF (three dose groups, 8.5, 17, and 22.1 g/kg) by gavage for 14 days, and cyclophosphamide (80 mg/kg) was injected on days 10-12. Only injection of cyclophosphamide (negative control) or physiological saline (blank control) were included as controls. The spleen and femur were processed for histopathology. Active components and the target of SXF were screened. The target was used for gene enrichment and protein-protein interaction (PPI) analysis. RESULTS: Red blood cell relative changes in the SXF group (low: -5.50 ± 1.58%; medium: -11.11 ± 4.15%; high: -8.81 ± 2.67%) and relative negative control (26.21 ± 2.51%) significantly increased (all p < 0.01) in female mice. Haemoglobin and red blood cell-specific volume showed the same trend. However, SXF did not have significant effects on male mice. Splenic index in the medium group (4.44 ± 0.46%) relative negative control (3.38 ± 0.10%) significantly improved (p < 0.01) in female mice. Using network pharmacology, 77 active components and 337 targets were screened from SXF. These targets are closely related to the mitogen-activated protein kinase pathway. CONCLUSIONS: SXF has good clinical application potential. However, the mechanism requires in-depth research. Our findings are of great significance in anaemia treatment and provide a new perspective for Chinese medicine research.

Role of central PGE2 on sympathetic excitation in chronic heart failure / 中国病理生理杂志

AIM:To observe the effect of central prostaglandin E2(PGE2) on sympathetic activation in chronic heart failure (CHF) and to explore the underlying mechanism. METHODS:Male SD rats were subjected to coronary ar-tery ligation to induce heart failure (HF), and the intracerebroventricular infusion was performed by osmotic pump continu-ously. The rats in sham group and HF group were given artificial cerebrospinal fluid (0. 25 μL/h). The rats in HF plus treatment group was given celecoxib (CLB; 20 mg/h). After 4 weeks, the levels of PGE2 in cerebrospinal fluid ( CSF), the sympathetic nerve excitability and cardiac function were measured, and the changes of corticotropin-hormone releasing hormone ( CRH)-containing neurons activation and neurotransmitter contents in the hypothalamic paraventricular nucleus ( PVN) were also determined. RESULTS:Compared with the sham-operated rats, the HF rats had raised level of PGE2 in CSF, up-regulated renal sympathetic nerve activity and plasma norepinephrine, increased left ventricular end diastolic pres-sure, lung-to-body weight and right ventricular-to-body weight ratios, and decreased maximal increase and decreased rate of left ventricular pressure (P<0.05). In addition, the number of CRH positive neurons in PVN and the level of plasma ad-renocorticotropic hormone were higher in HF rats than those in sham-operated rats (P<0.05). After administration of CLB into the lateral ventricle of HF rats, the contents of PGE2 in CSF were significantly reduced, the number of activation CRH neurons in PVN was decreased, the excitability of sympathetic nerves was down-regulated and cardiac function was im-proved (P<0.05). Compared with the sham-operated rats, the content of glutamic acid in PVN of HF rats was increased, the content of γ-aminobutyric acid and the number of glutamate decarboxylase 67-positive neurons were decreased ( P<0.05). After the CLB was given, the above indexes were reversed (P<0.05). CONCLUSION:These findings indicate that in CHF, the increased central PGE2 may activate CRH-containing PVN neurons and contribute to the augmented sym-pathetic drive possibly by modulating the neurotransmitters within the PVN.

Activation of corticotrophin releasing hormone-containing neurons in hypothalamic paraventricular nucleus contributes to sympathoexcitation in rats with congestive heart failure / 中国病理生理杂志

AIM: To observe the expression of corticotropin releasing hormone (CRH) within the paraventricular nucleus of hypothalamus (PVN) and to explore the relationship between the activated CRH-containing neurons and sympathetic activity in rats with heart failure (HF).METHODS: Healthy male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to induce HF, and chronic intracerebroventricular (ICV) infusion was performed by osmotic pump for 4 weeks.The rats in sham group and HF group were given vehicle (VEH;artificial cerebrospinal fluid 0.25 μL/h).The rats in HF plus treatment group were treated with CRH competitive inhibitor αh-CRH (15 mg/h).Meanwhile, the Lewis rats and Fischer 344 rats for control study also underwent coronary ligation to induce HF or sham surgery.After 4 weeks, left ventricular end-diastolic pressure (LVEDP) and maximum positive/negative change in pressure over time (±dp/dtmax) were determined.The right ventricular-to-body weight (RV/BW) and lung-to-body weight (lung/BW) ratios were calculated.The renal sympathetic nerve activity (RSNA) was recorded and the plasma norepinephrine (NE) level was measured.The expression of CRH in the PVN combined with the plasma adrenocorticotrophic hormone (ACTH) levels were measured.RESULTS: Compared with the sham-SD rats, the HF-SD rats had a greater number of CRH positive neurons in the PVN (accordingly the plasma ACTH levels were increased), accompanied by decreased ±dp/dtmax and increased RSNA, plasma NE, LVEDP, lung/BW and RV/BW.However, ICV treatment with αh-CRH attenuated these changes in the HF-SD rats (P<0.05).Compared with the sham-Fisher 344 rats, the HF-Fisher 344 rats also had a greater number of CRH positive neurons in the PVN (accordingly the plasma ACTH levels were increased).In addition, they had significantly increased RSNA and plasma NE level, higher LVEDP, RV/BW and lung/BW, and lower ±dp/dtmax (P<0.05).Compared with the SHAM-Lewis rats, the HF-Lewis rats had not significantly changed in the above parameters.CONCLUSION: In CHF, the CRH-containing neurons in PVN are activated, thus aggravating cardiac function by increasing sympathoexcitation.