Objective: To investigate the effects of aerobic exercise on non-alcoholic fatty liver (NAFLD) induced by high fat and the mechanism of CNPY2-PERK pathway. Methods: Eight-week-old male C57BL/6J mice were randomly divided into four groups: the control group (C), the C+ aerobic exercise group (CE), the model group (M) and the M+ aerobic exercise group (ME). Mice in group C and CE were given normal diet, while mice in group M and ME were given high-fat diet (60 cal % fat). The mice were fed continuously for 18 weeks until the end of the experiment, and the serum and liver samples were collected. Both CE and ME group performed an aerobic treadmill training from the 10th week (12 m/min, 60 min/ day, 5 days/week, for 8 weeks). The serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), alanine aminotransferase (ALT), aspartate aminotransferase (AST) were detected. The pathological morphology of the liver was observed. The relative expressions of CNPY2, PERK, p-eIF2a, CHOP, CNPY2 mRNA and PERK mRNA, and the positive expressions of CNPY2 and PERK were measured. Results: Compared with group C, the serum levels of LDL-c, TC, TG, ALT and AST in group M were increased significantly (P＜0.05), while the HDL-c level was decreased significantly (P＜0.05). The liver tissues of mice showed obvious hepatic steatosis, the number of lipid droplets in liver cells was increased, and the expressions of CNPY2, CNPY2mRNA, PERK, PERKmRNA, p-eIF2a, CHOP, and the positive expressions of both CNPY2 and PERK in liver were increased (P＜0.05). However, the above indexes showed no significant difference in CE group (P＞0.05). Compared with group M, the serum levels of LDL-c, TC, TG, ALT and AST in group ME were decreased (P＜0.05). The fatty degeneration of liver tissue and the number of lipid droplets in liver cells in mice was reduced, and the expressions of CNPY2, CNPY2 mRNA, PERK, PERK mRNA, p-eIF2a, CHOP, and the positive expressions of CNPY2 and PERK in liver tissue were decreased (P＜0.05). Conclusion: The CNPY2-PERK pathway is involved in the formation of NAFLD. Aerobic exercise can effectively ameliorate NAFLD, and the mechanisms may be related to the reduction of CNPY2-PERK pathway-related molecule expressions by aerobic exercise.
Animals ; Cholesterol, LDL ; Exercise ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease ; RNA, Messenger ; Triglycerides

Objective: To investigate the effects of different prescription compositions of traditional Chinese medicine and its different extraction methods of compound formula extracts on hypoxia tolerance in mice, in order to preferably select their prescription compositions and preparation extraction methods. Methods: Male BALB/c mice were randomly divided into 6 groups: blank control group, compound danshen group, compound Rhodiola Rosea alcohol-water extract group (Rhodiola rosea, Astragali Radix, Polygonati Rhizoma, Lycii Fructus), compound Rhodiola Rosea water extract group, compound Astragalus alcohol-water extract group (Astragali Radix, Polygonati Rhizoma, Lycii Fructus) and compound Astragalus water extract group, 30 mice in each group. Each group was administered continuously by gavage for 10 d. The blank group was gavaged with sterilized injection water. The mice in the other groups were treated with 0.15 g/kg of compound danshen, 3 g/kg of compound Rhodiola Rosea alcohol-water extract or water extract, and 1.7 g/kg of compound Astragalus alcohol-water extract or water extract, respectively. Each group was subjected to normobaric hypoxia tolerance test, sodium nitrite toxicity survival test and acute cerebral ischemia-hypoxia test 1 h after the last gavage, and the mice brain tissues were used to determine the activity of antioxidant enzymes and metabolites related to oxidative stress. Results: Compared with the blank control group, in normobaric hypoxia tolerance test, the survival time of mice in the compound danshen group and the compound Astragalus alcohol-water extract group and water extraction group was prolonged significantly (P＜0.01), and the number of open-mouth gasping after cerebral ischemia and hypoxia was increased significantly (P＜0.05). There was no statistical difference in survival time after sodium nitrite injection in each group. Compared with the blank control group, the activities of T-AOC, SOD, GSH and CAT were increased significantly (P＜0.05, P＜0.01) and the content of MDA was decreased significantly (P＜0.01) in the compound Astragalus water extract group. Compared with the compound danshen group, the activities of SOD, CAT and GSH were increased significantly (P＜0.01, P＜0.05) and the content of MDA was decreased significantly (P＜0.05). Conclusion: Compound Astragalus water extraction has the best effect of hypoxia tolerance, compound Rhodiola Rosea can eliminate Rhodiola rosea and consists of Astragali Radix, Polygonati Rhizoma, Lycii Fructus and its extraction method is water extraction.
Animals ; Astragalus Plant ; Ethanol ; Hypoxia ; Male ; Mice ; Plant Extracts/pharmacology* ; Rhodiola ; Sodium Nitrite ; Superoxide Dismutase/metabolism* ; Water

Altitude ; Exercise/physiology* ; Heart Rate/physiology* ; Humans ; Lung ; Respiration

Objective: To investigate the effects of continuing exercise and load-bearing interval exercise on skeletal muscle tissue cell morphology, Ras-related proteins 5 (Rab5) mRNA and protein expression and glucose metabolism in skeletal muscle of type 2 diabetic mellitus (T2DM) rats. Methods: Eight SD rats were selected as controls group (CR), the others SD rats were fed with high fat and high sugar diet for 6 weeks before injecting STZ (35 mg/kg) to construct the T2DM model. Twenty-four T2DM rats were randomly devided into T2DM model group (DRM), continuing exercise group (DCRE) and load-bearing interval exercise group (DWRE), 8 rats in each group. DCRE exercise protocol, that was 15 m/min (10 min), 20 m/min (40 min), 15 m/min (10 min), during the first 1～2 weeks, and 18 m/min (10 min), 25 m/min (40 min), 15 m/min (10 min), during the second 3～8 weeks. DWRE exercise protocol: load weight 15% / 1～2 weeks, 30% / 3～4 weeks, 45% / 5～8 weeks, with 15 m/min (5 min), 12 groups and 3 min rest between groups. After 8 weeks, pathological and morphological changes of skeletal muscle were observed by HE. Rab5 and Glucose transporte 4 (GLUT4) mRNA expressions of skeletal muscle were tested by qRT-PCR. Rab5 protein expression in skeletal muscle was tested by immunofluorescence histochemistry and Western blot, and plasma Rab5 and Glycosylated Hemoglobin (GHb) concentrations were detected by ELISA. Results: Comparison with CR, DRM showed pathological damage of skeletal muscle, the expressions of Rab5 mRNA, protein and GLUT4 mRNA were all decreased in skeletal muscle (P＜0.01), the serum levels of Rab5 and GHb were both significantly elevated (P＜0.01). Comparison with DRM, both DCRE and DWRE significantly improved pathological damages of skeletal muscle, the expressions of Rab5 mRNA, protein and GLUT4 mRNA were all increased in skeletal muscle (P＜ 0.05, P＜0.01), the serum levels of Rab5 and GHb were decreased (P＜0.05, P＜0.01), and there was no statistical difference between DCRE and DWRE groups (P＞0.05). Conclusion: Two exercise modes can improve the pathological injury of skeletal muscle in type 2 diabetic rats, and enhance GLUT4 transport capacity by improving the expression of Rab5 gene and protein in skeletal muscle, and alleviate the imbalance of glucose metabolism homeostasis in skeletal muscle. However, there was no significant difference between the effects of two exercise modes on Rab5 protein and glucose metabolism in skeletal muscle.
Animals ; Diabetes Mellitus, Experimental/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Glucose/metabolism* ; Glycated Hemoglobin ; Insulin ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal/methods* ; RNA, Messenger/metabolism* ; Rats ; Rats, Sprague-Dawley ; rab5 GTP-Binding Proteins/metabolism*

Objective: To study the effects of aerobic exercise training on renal fibrosis in spontaneously hypertensive rats (SHR), and to explore the protective effect of exercise on renal damage in hypertensive rats. Methods: Eight-week-old male SHR and Wistar Kyoto rats of the same age (WKY) were randomly divided into 4 groups (n=6): sedentary WKY control group (WKY-S), sedentary SHR control group (SHR-S), low-intensity exercise group (SHR-L) and medium-intensity exercise group (SHR-M). SHR-L group and SHR-M group were set at a slope of 0° at 14 m/min (35% of the maximum aerobic speed) and 20 m/min (50% of the maximum aerobic speed), running on a sports treadmill for 14 weeks, 5 times a week, and 60 min each time. WKY-S and SHR-S groups were kept quietly. Blood pressure was measured 72 hours after exercise training. And the serum levels of creatinine (Scr) and BUN were detected. The morphology of renal tissue was observed by hematoxylin and eosin (HE) staining. The collagen deposition of renal tissue was observed by Masson staining, and the renal collagen volume fraction (CVF) was calculated. Results: Compared with WKY-S group, blood pressure, serum Scr and BUN, kidney CVF levels and AngⅡ, AT1R, TGF-β, α-SMA, CTGF expressions in SHR-S group were increased significantly (P＜0.05). Compared with SHR-S group, blood pressure, serum Scr and BUN, kidney CVF level and AngⅡ, AT1R, TGF-β, α-SMA, CTGF expressions in SHR-L and SHR-M groups were decreased significantly (P＜0.05) and the decreasing trend was more obvious in SHR-M group (P＜0.05). Conclusion: Aerobic exercise can improve renal fibrosis and renal function in spontaneously hypertensive rats by inhibiting the AngⅡ-AT1R-TGF-β pathway.
Animals ; Fibrosis ; Kidney Diseases ; Male ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Transforming Growth Factor beta

Aged ; Humans ; Lower Extremity ; Middle Aged ; Muscle, Skeletal/physiology* ; Vibration

Objective: To investigate the role of clock gene BMAL1 in exercise-induced skeletal muscle injury recovery. Methods: Two hundred and eight 8-week-old SD rats were randomly divided into the control group (Group C, n=104) and the exercise group (Group E, n=104). Group E performed a 90-minute downhill run on the treadmill. After exercise, the gastrocnemius muscle of 8 rats in Group C and Group E were collected at 0 h, 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h, 66 h and 72 h. The expression of skeletal muscle core clock gene, BMAL1 was measured by real-time fluorescence quantitative PCR. The parameters of fitting cosine curve were obtained by cosine analysis software circacompare (R package), and the change trend of rhythmic oscillation was analyzed. The ultrastructure of skeletal muscle fibers was observed by transmission electron microscope. The expressions of skeletal muscle BMAL1 and DESMIN were detected by Western blot; Immunofluorescence was used to observe the localization and contents of BMAL1 and DESMIN. Results: In Group C, three complete circadian rhythm cycles of mRNA BMAL1 were observed within 72 hours; in Group E, the circadian rhythm of BMAL1 mRNA disappeared at 0 h～24 h. Compared with Group C, the expression level of BMAL1 mRNA was significantly increased at 0 h, 6 h, 12 h, and 18 h after exercise in Group E (P＜0.05), and the expression of BMAL1 protein was significantly increased at 0 h and 12 h after exercise(P＜0.05), and recovered to the level of that in Group C from 24 h to 72 h(P＞0.05). The expression of DESMIN protein was decreased at 0 h and 12 h after exercise(P＜0.05), gradually increased at 24 h, increased significantly at 48 h(P＜0.01), and recovered to the control level at 72 h (P＞0.05). In Group E, BMAL1 and DESMIN were co-localized at 0 h, 12 h, and 24 h after exercise; the colocalization at 0 h～24 h showed a trend of first decreasing and then increasing, and the fluorescence intensity at 24 h reached the highest value. Conclusion: The post-exercise clock gene BMAL1 may be involved in the enhanced synergy of regulating the cytoskeletal protein DESMIN, it is thus related to the promotion of muscle fiber structure recovery.
ARNTL Transcription Factors/metabolism* ; Animals ; Desmin/metabolism* ; Muscle, Skeletal/physiology* ; Physical Conditioning, Animal/adverse effects* ; RNA, Messenger/metabolism* ; Rats ; Rats, Sprague-Dawley

Objective: To investigate the protective effects of Polygonatum odoratum polysaccharides (POP) on alcohol-induced injury of HepG2 cells and its potential molecular mechanisms. Methods: After screening the appropriate concentration of alcohol-treated HepG2 cells and the intervention concentration of POP by MTT method, HepG2 cells were divided into three groups according to different intervention concentrations (200 μg/L, 400 μg/L and 600 μg/L) of POP, and the blank group without POP. After pretreated for 1 h, HepG2 cells were treated with 4% alcohol for 24 h. The activities of intracellular alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and the levels of intracellular reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF- α) were measured. The protein expressions of Kelch-like epichlorohydrin-associated protein-1 (Keap1), phosphorylated nuclear factor E2-related factor 2 (p-Nrf2), phosphoamide adenine dinucleotide quinone oxidoreductase -1 (NQO1), B lymphocyte tumor-2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase 3 were detected. Results: Compared with the HepG2 cells treated with 4% alcohol, POP at the various concentrations could effectively down-regulate the activities of ALT and AST in HepG2 cells induced by alcohol (P＜0.05). The levels of IL-1β and TNF-α in the 200 μg/L POP treated group were decreased significantly (P＜0.05), while the level of GSH was increased significantly (P＜0.01). The levels of ROS, MDA, IL-1β and TNF-α in the 400 μg/L and 600 μg/L POP treated groups were decreased significantly (P＜0.05 or P＜0.01), while the GSH level was increased significantly (P＜0.01). POP effectively up-regulated the expressions of p-Nrf2 and NQO1 protein in HepG2 cells induced by alcohol, and also down-regulated the Bax/Bcl-2 index (P＜0.05), and inhibited the protein expressions of Keap1 and cleaved-caspase-3 (P＜0.05). Conclusion: POP can improve alcohol-induced oxidative stress injury in HepG2 cells by regulating the Nrf2/Keap1 pathway, thereby reducing the inflammatory index and apoptosis level of HepG2 cells. Among them, 400 μg/L and 600 μg/L POP have better intervention effects.
Ethanol ; Hep G2 Cells ; Humans ; Kelch-Like ECH-Associated Protein 1/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Polygonatum/metabolism* ; Polysaccharides/pharmacology* ; Reactive Oxygen Species/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; bcl-2-Associated X Protein/metabolism*

Objective: To investigate the effects of cadmium (Cd) on antioxidant enzymes in testis of mice and the protective effect of vitamin C (VC). Methods: A total of 72 male Kunming mice of clean grade were divided into four groups (n=18): the control group, the Cd group (CdCl₂ 3 mg/kg), the VC group (200 mg/kg), and the VC (200 mg/kg) +Cd group (CdCl₂ 3 mg/kg). Mice were poisoned once a day, exposed for 1 and 3 days and were treated with VC at the same time. Twenty-four hours after exposure on the 1st and 3rd day, half of the mice in each group were weighed, the serum and testis tissues were collected. Testicular organ coefficient, malondialdehyde (MDA) and superoxide dismutase (SOD) in serum and testis tissues, and glutathione peroxidase (GSH-Px), reduced glutathione (GSH), oxidized glutathione (GSSG) and total glutathione (T-GSH) in testis tissues were detected. Results: Compared with the control group, the body weight and testicle organ coefficient of mice in the Cd group were decreased on the 1st and 3rd day; after 3 days of exposure, the serum SOD in the Cd group was decreased significantly and MDA was increased significantly (P＜0.05); the levels of SOD, GSH-Px, T-GSH and GSH/GSSG of testis in the Cd group were increased significantly on the 1st day (P＜0.05), while all the above indexes were decreased significantly on the 3rd day (P＜0.05), and the content of MDA was increased significantly on the 1st and 3rd days in the Cd group (P＜0.05); after VC treatment, the degree of reduction was decreased. Compared with the Cd group, the serum SOD and MDA levels in the VC+ Cd group were significantly different after 3 days of exposure (P＜0.05); the changes of SOD, GSH-Px, T-GSH and GSH/GSSG levels of the testis in the VC+ Cd group were significantly different on the 1st and 3rd day of exposure (P＜0.05), and the MDA level of the testis in the VC+ Cd group was decreased significantly on the 3rd day of exposure (P＜0.05). Compared with the Cd group for 1 day, the level of serum SOD exposed for 3 days was decreased significantly (P＜0.05), and the changes of testis indexes were also significantly different (P＜0.05). Conclusion: VC treatment can improve the antioxidant function of cadmium-loaded mice to some extent, and has protective effect on oxidative damage of testis.
Animals ; Antioxidants/pharmacology* ; Ascorbic Acid/pharmacology* ; Cadmium/toxicity* ; Glutathione ; Glutathione Disulfide/pharmacology* ; Glutathione Peroxidase ; Male ; Superoxide Dismutase ; Testis

Animals ; Dentate Gyrus ; Hippocampus ; Rats ; Receptors, Adrenergic, beta ; Sleep ; Spatial Learning