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Through the non-targeted metabolomics study of endogenous substances in the liver and serum of hyperlipidemia rats, the biomarkers related to abnormal lipid metabolism in hyperlipidemia rats were found, and the target of ginsenoside Rb_1 in improving hyperlipidemia was explored and its mechanism was elucidated. The content of serum biochemical indexes of rats in each group was detected by the automatic biochemical analyzer. The metabolite profiles of liver tissues and serum of rats were analyzed by HPLC-MS. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to compare and analyze the metabolic data in the normal group, the hyperlipidemia group, and the ginsenoside Rb_1 group, and screen potential biomar-kers. The related metabolic pathways were further constructed by KEGG database analysis. The results showed that hyperlipemia induced dyslipidemia in rats, which was alleviated by ginsenoside Rb_1. The non-targeted metabolomics results showed that there were 297 differential metabolites in the liver tissues of hyperlipidemia rats, 294 differential metabolites in the serum samples, and 560 diffe-rential metabolites in the hyperlipidemia rats treated by ginsenoside Rb_1. Perillic acid and N-ornithyl-L-taurine were common metabolites in the liver and serum samples, which could be used as potential biomarkers for ginsenoside Rb_1 in the improvement of hyperlipidemia. As revealed by pathway enrichment in the liver and serum, ginsenoside Rb_1 could participate in the metabolic pathway of choline in both the liver and serum. In addition, ginsenoside Rb_1 also participated in the ABC transporter, alanine, aspartic acid, and glutamate metabolism, protein digestion and absorption, β-alanine metabolism, taurine and hypotaurine metabolism, caffeine metabolism, valine, leucine, and isoleucine biosynthesis, arachidonic acid metabolism, and methionine and cysteine metabolism to improve dyslipidemia in rats.
Subject(s)
Rats , Animals , Hyperlipidemias/drug therapy , Metabolome , Ginsenosides/metabolism , Lipid Metabolism , Metabolomics/methods , Liver/metabolism , Biomarkers , TaurineABSTRACT
@#Objective To analyze the clinical laboratory indicators of severe fever with thrombocytopenia syndrome( SFTS) patients caused by novel Bunyavirus infection，and focus on comparing the indicators of severe patients with different prognosis． The findings may help to predict poor prognosis for severe patients in the early stage． Methods The clinical laboratory indicators of all diagnosed confirmedly patients in two Hospitals，from January 2011 to December 2018，and the differences between groups were analyzed．Ｒesults A total of 168 clinically diagnosed SFTS cases ( 117 cases of non－severe cases and 51 cases of severe cases) were included in this study． In the severe cases，the prognosis was improved in 30 cases and the prognosis was poor in 21 cases． The laboratory indicators of severe patients with different prognosis were compared． The data showed that the levels of several indicators in patients with poor prognosis were statistically different with these in patients with better prognosis． In addition，the proportion of coma，diffuse intravascular coagulation and heart failure in patients with poor prognosis was significantly higher than that in patients with improved prognosis ( all P＜0. 05) ． Conclusion Differentiated prevention and treat- ment strategies should be developed for severe patients with possible poor prognosis．
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Objective: To investigate the expression changes of mitogen activated protein kinase(MAPK) signaling pathway-related genes in ApoE-/- mice and the intervention effect of Huayu Qutan recipe on them, in order to explore the anti-atherosclerotic(AS) effect and possible mechanism of Huayu Qutan recipe. Method: Fifty ApoE-/- mice were randomly divided into model group, tanshinone ⅡA group (30 mg·kg-1·d-1), and high-dose phlegm group (20 g·kg-1·d-1), the middle-dose group (10 g·kg-1·d-1), and the low-dose group (5 g·kg-1·d-1), and 10 C57BL/6/J mice were included in the blank controls group. Automated biochemical analyzer was used to detect serum triglyceride(TG), cholesterol(TC), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C) content; hematoxylin-eosin(HE) was used to detect aortic plaque in each group; oil red O was used to detect liver lipid deposition in each group; enzyme-linked immuno sorbent assay(ELISA) was used to determine vascular cell adhesion protein-1(VCAM-1), intercellular adhesion molecule-1(ICAM-1), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) in serum of each group; Western blot was performed to detect c-Jun N-terminal kinase (JNK), phosphorylated c-Jun N-terminal kinase(p-JNK), c-Jun N-terminal kinase(JNK), p38 MAPK, p-p38 MAPK, extracellular regulated protein kinases (ERK), and expression of p-ERK. Result: Compared with the blank control group, serum TC, TG, LDL-C levels in the model group were significantly increased, while HDL-C levels were significantly decreased; aortic plaques were observed in the aortic lumen, and lots of lipid deposition were observed in the liver cells. Serum inflammatory factors TNF-α, IL-6, VCAM-1, ICAM-1 increased(PPα, IL-6, VCAM-1 and ICAM-1 were decreased. The expressions of p-p38 MAPK and p-JNK genes in intravascular associated MAPK signaling pathway were significantly decreased. p-ERK expression trend was not obvious(PConclusion: Huayu Recipe can inhibit the formation of aortic plaque in ApoE-/- mice, and its mechanism may be related to the regulation of vascular MAPK signaling pathway gene expression.
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Aim To observe the protective effect of ginsenoside Re pretreatment on rats with isoproterenol-induced acute myocardial ischemia via JAK 2/STAT3 signaling pathway .Methods SD rat model with acute myocardial ischemia was established using isoprotere-nol.Seventy-five rats were randomly divided into five groups: control group, model group , puerarin group (PUE), high dose group (Re-H, 20 mg· kg -1) and Re low-dose group ( Re-L, 10 mg kg -1 ) .The blood flow on the heart surface of rats in each group was ob-served by moor laser blood flow imaging system .The levels of CK , LDH, SOD, MDA and GSH in myocar-dium were measured by ELISA .The expressions of Bax and Bcl-2 proteins were detected by immunohistochem-istry.The expressions of JAK , p-JAK, STAT3 and p-STAT3 proteins were detected by Western blot .Re-sults Compared with the control group , the mean blood flow on the heart surface of rats in the model group significantly decreased , the levels of CK , LDH and MDA in the myocardium increased , the levels of GSH and SOD decreased , the ratio of Bcl-2/Bax de-creased ( P <0.05 ) , and the expression of JAK 2/STAT3 pathway related proteins was enhanced ( P <0.05 ) . The mean blood flow on the heart surface markedly increased , the levels of CK , LDH and MDA decreased , the level of GSH-Px increased , the ratio of Bcl-2/Bax increased, and the expression of JAK2/STAT3 pathway proteins evidently increased in the Re-H group compared with those of the model group ( P<0.05 ) .Conclusion Ginsenoside Re pretreatment has a good protective effect on the myocardium in rats with acute myocardial ischemia , which may be related to the activation of JAK2/STAT3 signaling pathway .
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Objective To construct a three-dimensional (3D) solid model of the cortical bone including osteons, verify the stress concentration effect of osteons, simulate and predict the stress concentration location under fatigue using finite element analysis (FEA). Methods The 3D solid model of the cortical bone including osteons was constructed in Pro/E wildfire 5.0, and local stress and strain distributions in the cortical bone under different axial compression were calculated and analyzed in ANSYS 12.0. Fatigue simulation on the selected locations was conducted to evaluate fatigue status of the model subjected to different fatigue loading intensities. Results Obvious stress concentration at the junction of osteon and the interstitical bone appeared under axial compressive loads, and the percentage of pathological local strain in the cortical bone increased with the axial compression increasing. Fatigue simulation on the selected locations demonstrated that bone fatigue risk during physiological or daily activities was very low, while a high fatigue or fracture risk might occur during high-intensity exercises or training. Conclusions The 3D solid model of the cortical bone including osteons is successfully established, the stress concentration effect of osteons is verified, and the location of bone fatigue damage under strenuous exercise and its risk are predicted. These experimental results can provide references for training management and athletic fatigue damage prevention in military recruits and long distance running athletes.
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Objective To construct a three-dimensional (3D) solid model of the cortical bone including osteons,verify the stress concentration effect of osteons,simulate and predict the stress concentration location under fatigue using finite element analysis (FEA).Methods The 3D solid model of the cortical bone including osteons was constructed in Pro/E wildfire 5.0,and local stress and strain distributions in the cortical bone under different axial compression were calculated and analyzed in ANSYS 12.0.Fatigue simulation on the selected locations was conducted to evaluate fatigue status of the model subjected to different fatigue loading intensities.Results Obvious stress concentration at the junction of osteon and the interstitical bone appeared under axial compressive loads,and the percentage of pathological local strain in the cortical bone increased with the axial compression increasing.Fatigue simulation on the selected locations demonstrated that bone fatigue risk during physiological or daily activities was very low,while a high fatigue or fracture risk might occur during high-intensity exercises or training.Conclusions The 3 D solid model of the cortical bone including osteons is successfully established,the stress concentration effect of osteons is verified,and the location of bone fatigue damage under strenuous exercise and its risk are predicted.These experimental results can provide references for training management and athletic fatigue damage prevention in military recruits and long distance running athletes.
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AIM:To observe the influence of Lycium barbarum polysaccharide (LBP) on the PI3K/Akt/eNOS signaling pathways in ovariectomized rat myocardium .METHODS:Female SD rats (n=30) were divided into sham oper-ation group , ovariectomized group , progynova group , high-dose LBP group and low-dose LBP group .The serum levels of estradiol, lactate dehydrogenase (LDH) and creatine kinase (CK) were measured by ELISA.The myocardial contents of H2 S and oxidative stress injury-related indicators were also detected .The morphological changes of the myocardium were observed with HE staining.The expression of eNOS and PI3K/Akt pathway-related proteins in the myocardium was deter-mined by Western blot .RESULTS: Compared with sham operation group , the serum level of estradiol , the content of H2 S, the activity of GSH-Px, and the expression of eNOS and PI3K/Akt pathway-related proteins in the myocardium in ovariectomized group were all decreased , and the levels of ROS and MDA in the myocardium were increased (P<0.05). The serum levels of LDH and CK were also increased .The arrangement of the myocardial cells was disordered , and the in-tercellular space was also increased in the ovariectomized group .Compared with ovariectomized group , the serum level of estradiol, the myocardial levels of H2S and GSH-Px, and the protein levels of eNOS and phosphorylated Akt were all in-creased in high dose group, while the levels of ROS and MDA in the myocardium were decreased (P<0.05).The serum levels of LDH and CK were also decreased .The morphological changes of the rat myocardium were improved in high dose group.CONCLUSION: LBP prevents and treats postmenopausal cardiovascular lesions through regulating PI 3K/Akt/eNOS signaling pathways in ovariectomized rats .
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Objective To investigate the application value of Atlas titanium cable in the treatment of comminuted patellar fractures (CPF).Methods 80 patients with CPF in our hospital from January, 2010 to January, 2013 were randomly selected and divided into observation group (n=40) and control group (n=40) by digital random method.Observation group adopted Atlas tita-nium cable internal fixation treatment while control group adopted the improved tension band steel wire in the hollow compression screws fixation treatment.Preoperative (t0), postoperative 1 month (t1), 6 months (t2) and 1 year (t3) Bostman patellar injury curative effect score (BPICES), operation time, intraoperative blood loss, postoperative knee joint exercise time for the first time, length of hospital stay, treatment costs and complications of two groups were compared.Results Preoperative BPICES of two groups had no statistical significant difference (p>0.05).Compared with t0, t2 and t3 BPICES and the rate of optimal curative effects, two groups increased; Compared with the control group, t2 and t3 BPICES and the rate of optimal curative effects of observation group also increased, and the difference was statistically significant (p<0.05).Operation time, intraoperative blood loss, postoperative knee joint exercise time for the first time, length of hospital stay of observation group were (52.26 ±10.29) min, (70.48 ±10.49) ml, (4.78 ±1.48) d and (5.98 ±1.06) d respectively, which were lower than the (79.95 ±8.42) min, (123.36 ±21.18) ml, (9.14 ±4.48) d and (11.18 ±2.68) d of the control group;Therapy cost of observation group was (16 284.47 ±2 145.78) Yuan, which was higher than the (9 892.48 ±1 456.42) Yuan of the control group (p <0.05).Compared with control group, peptide wire/wire Piercing the skin, pain, infection, skin irritation, slippery bursa phlogistic, internal fixation of fracture parted, fracture end separation and other complications total incidence of observation group were lower (p<0.05).Conclusion Atlas titanium wire trea-ting of patients with CPF had shorter operation time and hospitalization time , less postoperative complications.It can promote the rapid recovery of knee joint function, but its cost is higher.Thus it is suitable for CPF patients with better economic conditions .
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<p><b>OBJECTIVE</b>To explore the intervention of Huayu Qutan Recipe (HQR) on liver SREBP-2 signal pathway of hyperlipidemia rats of Pi deficiency syndrome (PDS).</p><p><b>METHODS</b>Totally 100 SPF grade SD rats were randomly divided into the blank control group, the hyperlipidemia group, the hyperlipidemia treatment group, the PDS hyperlipidemia group, and the PDS hyperlipidemia treatment group, 20 in each group. Common granular forage was fed to rats in the blank control group. High fat forage was fed to rats in the hyperlipidemia group and the hyperlipidemia treatment group. Rats in the PDS hyperlipidemia group and the PDS hyperlipidemia treatment group were treated with excessive labor and improper diet for modeling. They were administered refined lard by gastrogavage (3 mL each time, twice per day) and fed with high fat forage on the odd days, and fed with wild cabbage freely on even days. The modeling lasted for 30 days. Rats in the hyperlipidemia treatment group and PDS hyperlipidemia treatment group were administered with Huayu Qutan Recipe (20 mL/kg) by gastrogavage, once a day, for 30 successive days. Levels of serum cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and serum amylase (AMY) were detected by automatic biochemical analyzer. D-xylose excretion rate was determined using phloroglucinol method. Morphological changes of liver and the lipid deposition in liver were observed using HE stain and oil red O stain respectively, mRNA and protein expression levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase 1 (CYP7A1), LDL-R, and sterol regulatory element binding protein-2 (SREBP-2) were detected using real time RT-PCR and Western blotting.</p><p><b>RESULTS</b>Compared with the blank control group, serum levels of TC (1.84 ± 0.19 mmol/L, 2.23 ± 0.43 mmol/L) and LDL-C (0.99 ± 0.24 mmol/L, 1.13 ± 0.56 mmol/L) were higher in the hyperlipidemia group and the PDS hyperlipidemia group, serum levels of HDL-C (0.41 ± 0.66 mmol/L, 0.41 ± 0.11 mmol/L) and AMY activities (351 ± 45 mmol/L, 153 ± 30 mmol/L) were lower, and urinary D-xylose excretion rates were lower (26.9 ± 2.1 ng/mL, 15.0 ± 1.7 ng/mL) (all P < 0.05). Lipid deposition occurred in liver cells. Much fat vacuoles occurred in the cytoplasm. Expression levels of HMGCR, CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver significantly decreased (P < 0.01). Compared with the hyperlipidemia group, serum levels of TC and LDL-C significantly increased (P < 0. 05), AMY activities and urinary D-xylose excre- tion rates significantly decreased in the PDS hyperlipidemia group (P < 0.01). A large amount of lipid deposition occurred in liver. The atrophy of liver cells was obviously seen. Expression levels of CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly lower (P < 0.01, P < 0.05). Serum levels of TC and LDL-C significantly decreased (P < 0.05), AMY activities and urinary D-xylose excretion rates significantly increased in the hyperlipidemia treatment group (P < 0.01). Expression levels of CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly increased (P < 0.01, P < 0.05). Compared with the PDS hyperlipidemia group, serum level of TC significantly decreased (P < 0.05), HDL-C levels, AMY activities and urinary D-xylose excretion rates significantly increased in the PDS hyperlipidemia treatment group (P < 0.01),expression levels of CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly increased (P < 0.01). Similar changes occurred in the two treatment groups.</p><p><b>CONCLUSIONS</b>Pi deficiency exacerbates abnormal serum TC level and the lipid deposition in liver. These might be related to regulating expression levels of LDL-R, HMGCR, and CYP7A1 genes in the SREBP-2 signal pathway. HQR could regulate this pathway to intervene abnormal metabolism of TC.</p>
Subject(s)
Animals , Male , Rats , Cholesterol, HDL , Cholesterol, LDL , Drugs, Chinese Herbal , Therapeutic Uses , Hyperlipidemias , Drug Therapy , Liver , Medicine, Chinese Traditional , RNA, Messenger , Rats, Sprague-Dawley , Signal Transduction , Sterol Regulatory Element Binding Protein 2 , Metabolism , TriglyceridesABSTRACT
<p><b>OBJECTIVE</b>To investigate the dynamic expression of Heat shock protein 70 (Hsp70) in the lungs and plasma of rats with pulmonary fibrosis induced by silicon dioxide (SiO2).</p><p><b>METHODS</b>Forty-eight Wistar rats were randomly divided into the control group exposed to normal solution and group exposed to SiO2 (50 mg/ml) with intratracheal injection. Each group was divided into four subgroups. The animals of SiO2 group and control group were sacrificed and lungs were collected on the 7th, 14th and 28th days after exposure, respectively. The left lung tissues were examined with the histopathologic HE staining. The expression and localization of Hsp70 protein in the lung tissues were examined with western blot assay and immunohistochemistry, respectively. The expression levels of Hsp70 protein in the plasma were measured by ELISA.</p><p><b>RESULTS</b>The expression of Hsp70 in lung tissues of SiO2 group increased on the 7th day and reached the peak value on the 14th day then decreased, but still was significantly higher than that of the control group, the expression of Hsp70 in plasma of SiO2 group still was significantly higher than that of the control group (P < 0.05). The maximum expression level of Hsp70 in plasma of SiO2 group on the 21st day after exposure was 0.216 ± 0.027 µg/ml.</p><p><b>CONCLUSION</b>The expression levels of Hsp70 protein in the lung tissues and plasma of the group exposed to SiO2 significantly increased, which were associated with the process of pulmonary fibrosis. It was suggested that Hsp70 protein may play an important biological role in the pulmonary fibrosis induced by SiO2.</p>
Subject(s)
Animals , Male , Rats , HSP70 Heat-Shock Proteins , Blood , Metabolism , Lung , Metabolism , Pathology , Pulmonary Fibrosis , Metabolism , Rats, Wistar , Silicon Dioxide , ToxicityABSTRACT
<p><b>AIM</b>To explore the level of anti-HSP70 antibody in plasma during atherosclerosis procedure induced by high-fat diet in rat and the relationship of them.</p><p><b>METHODS</b>Twenty eight rat were divided into high-fat diet group (H) and control group (C). The total cholesterol (TC), Glyceride (TG), low density lipoprotein cholesterol (LDL-C) in serum, pathology change of rat Arch of the aorta were determined, the level of anti-HSP70 antibody and their Phenotype were evaluated by ELISA.</p><p><b>RESULTS</b>After two weeks, the serum concentrations of TC and LDL-C in rat supplemented by high-fat diet were significantly higher than those in control group (P < 0.01), the serum TG were much lower than those in control group (P < 0.01). Four weeks later the level of anti-HSP70 antibody, IgM, IgG phenotype were significantly higher than those in control group (P < 0.01). There were lipin deposition and mottling formation in rat Arch of the aorta in rat supplemented by high-fat diet in 12th week.</p><p><b>CONCLUSION</b>Atherosclerosis could be induced by high-fat diet in rat. Accompany with the atherosclerosis procession, the level of anti-HSP70 antibody was continuously elevated, the level of anti-HSP70 antibody was related to atherosclerosis. The level of anti-HSP70 antibody was closely associated with atherosclerosis.</p>