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1.
Acta Pharmaceutica Sinica ; (12): 1391-1399, 2021.
Article in Chinese | WPRIM | ID: wpr-887084

ABSTRACT

Our previous studies have shown that puerarin, an active component of the traditional Chinese medicine-Pueraria Lobata, can improve glycometabolism in high-fat diet (HFD) mice with diabetes by activating the glucagon-like peptide-1 receptor (GLP-1R) pathway. This study intends to further evaluate the effect of puerarin on depressive symptoms in HFD mice. Long-term HFD induces type 2 diabetes and depressive-like symptoms in mice. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine (approval No. AEWC-025). The experiment was divided into: control group, model group, model/puerarin (150 mg·kg-1·day-1) group, and model/fluoxetine (15 mg·kg-1·day-1) group. The oral glucose tolerance test (OGTT) and behavioral experimental analysis were performed after 6 weeks of continuous administration. Afterwards, enzyme-linked immunosorbent assay (ELISA) was used to detect interleukin-1β (IL-1β), interleukin-6 (IL-6), 5-hydroxytryptamine (5-HT), and corticosterone (CORT) in serum of mice for each group. Western blot assays were used to detect the level of activation and expression of proteins related to neuroplasticity and depressive disorder in the hippocampus. Moreover, HT-22 cell line was used to investigate the protective effect of puerarin on cell morphology and survival. The results show that puerarin can effectively maintain the survival of HT22 in an environment with high glucose and corticosterone. Meantime, the glycemic regulation of diabetic mice was improved after treatment of puerarin, the depressive symptoms were alleviated, the 5-HT increased, and the corticosterone, IL-1β, and IL-6 decreased in the serum. The up-regulation of related proteins in GLP-1R/Wnt/mTOR (mammalian target of rapamycin) signaling in hippocampus suggests that its effect on ameliorating depression in diabetic mice may be related to the activation of GLP-1R/Wnt/mTOR signaling pathway. This study shows that puerarin can significantly ameliorate the depressive symptoms of HFD induced diabetic mice which might be achieved through activating the GLP-1R/Wnt/mTOR signaling pathway and improving hippocampal neuroplasticity.

2.
Neuroscience Bulletin ; (6): 1427-1440, 2021.
Article in English | WPRIM | ID: wpr-922652

ABSTRACT

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.


Subject(s)
Animals , Mice , Astrocytes/metabolism , Complement C3/metabolism , Epilepsy , Neurons/pathology , Status Epilepticus , TRPV Cation Channels/metabolism
3.
Neuroscience Bulletin ; (6): 1427-1440, 2021.
Article in Chinese | WPRIM | ID: wpr-951952

ABSTRACT

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron–glia interaction mediated by the C3–TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3–TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.

4.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 885-890, 2015.
Article in English | WPRIM | ID: wpr-250325

ABSTRACT

Based on the recently proposed Chinese ischemic stroke subclassification (CISS) system, intracranial branch atheromatous disease (BAD) is divided into large artery atherosclerosis (LAA) and penetrating artery disease (PAD). In the current retrospective analysis, we compared the general characteristics of BAD-LAA with BAD-PAD, BAD-LAA with non-BAD-LAA and BAD-PAD with non-BAD-PAD. The study included a total of 80 cases, including 45 cases of BAD and 35 cases of non-BAD. Subjects were classified using CISS system: BAD-LAA, BAD-PAD, non-BAD-LAA and non-BAD-PAD. In addition to analysis of general characteristics, the correlation between the factors and the two subtypes of BAD was evaluated. The number of cases included in the analysis was: 32 cases of BAD-LAA, 13 cases of BAD-PAD, 21 cases of non-BAD-LAA, and 14 cases of non-BAD-PAD. Diabetes mellitus affected more non-BAD-LAA patients than BAD-LAA patients (P=0.035). In comparison with non-BAD-PAD, patients with BAD-PAD were younger (P=0.040), had higher initial NIHSS score (P<0.001) and morbidity of ischemic heart disease (P=0.033). Within patients with BAD, the PAD subtype was associated with smoking (OR=0.043; P=0.011), higher low-density lipoprotein (OR=5.339; P=0.029), ischemic heart disease (OR=9.383; P=0.047) and diabetes mellitus (OR=12.59; P=0.020). It was concluded that large artery atherosclerosis was the primary mechanism of BAD. The general characteristics showed no significant differences between the CISS subtypes of LAA and PAD within BAD, as well as between the BAD and non-BAD within LAA subtype. Several differences between PAD subtypes of BAD and non-BAD were revealed.


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Brain Ischemia , Pathology , China , Stroke , Pathology
5.
Chinese Journal of Experimental Ophthalmology ; (12): 432-436, 2011.
Article in Chinese | WPRIM | ID: wpr-635509

ABSTRACT

Background Trans-arachidonic acids (TAAs) are specific lipid markers of nitrative stress and the major products of NO2·-mediated ismoerization of aracchidonic acid(AA),and they represent a possible new mechanism of NO2·-induced toxicity in ischemic retinopathy.Our previous study demonstrated that high glucose induce nitrative stress response. Objective This study aimed to evaluate the effect of nitrative stress on retinal capillary in diabetic rats by detecting the TAAs with gas chromatography and mass spectrometry(GC/MS).Methods One hundred 2-week-old clean male SD rats were randomly divided into control group and diabetic group.Diabetic rat models were induced by intraperitoneal injection of streptozoticin of 60 mg/kg,and the successful models were identified as the blood glucose level>16.7 mmol/L.The synthesis method was modified in this study andaraehidonic acid w8$utilized as starting material.14E-AA was obtained as a standard sample via expoxidation and deoxidation in a safe and practical pattern.Serum TAAs and AA in diabetic rats were detected by GC/MS in 2,4,8,12 and 16 weeks after injection of streptozoticin.The ratio of peak area of TAAs to AA with selected ion of 79 was estimated and compared with normal rats. Results Fifty rats had been in Diabetic models were established in 50 rats with the successful rate 100%,and the high blood glucose level in model rats retained throughout the experimental duration.GC/MS results showed that the 14E-AA was obtained with the purity of 97.3%,which provided a standard sample to nitrative stress-related research as a premise. No significant differences were found in serum TAAs/AA values at 2 weeks and 4 weeks between model group and control group (t =-0. 376, t =-0. 642,P>0. 05). However,serum TAAs/AA values in at 8,12 and 16 weeks after streptozoticin injection were considerably elevated in comparison with those of control group (0. 0832 vs 0. 1042,0. 0910 vs 0. 1568, 0. 1100 vs 0. 1895;t=-36.409,t=-166.714,t=-148.212,P<0. 05). Conclusion Elevation of serum TAAs/AA is associated with diabetic duration,implying that damage of nitrative stress to retinal capillary is a parallel procedure to diabetic course.Establishment of GC/MS detection system offers a new evaluating indicator in the research on microvascular ischemic disease and could be implemented in clinical testing.

6.
Chinese Medical Journal ; (24): 1885-1889, 2011.
Article in English | WPRIM | ID: wpr-338572

ABSTRACT

<p><b>BACKGROUND</b>Trans-arachidonic acids (TAAs), newly discovered markers of nitrative stress and the major products of nitrogen dioxide (NO2(·))-mediated isomerization of arachidonic acid (AA), represent a new mechanism of NO2(·)-induced toxicity. It has been reported that TAAs were generated in oxygen-induced microvascular degeneration model and TAAs were also generated in a diabetic retinopathy (DR) model. In this study, we examined high glucose-induced nitrative stress damage and TAAs levels and explored the possible mechanisms for DR caused by reactive nitrogen species.</p><p><b>METHODS</b>Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) at 60 mg/kg. Bovine retinal capillary endothelial cells (BRECs) were selectively cultured and incubated with normal or high glucose. The serum TAAs and AA in diabetic rats were measured by the gas chromatography and mass spectrometry (GC/MS) method. The ratio of peak area of TAAs to AA with selected ion of 79 was estimated by a group t-test. Thrombospondin-1 (TSP-1) in the rat retinas and BRECs extracts were examined by Western blotting. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) protein was examined by Western blotting in BRECs incubated with high glucose.</p><p><b>RESULTS</b>The TAAs to AA ratio (TAAs/AA) was significantly increased in the serum at 8, 12 and 16 weeks after STZ injection (P < 0.05), with no noticeable change found at 2 or 4 weeks (P > 0.05). Expression of TSP-1 in the retina of diabetic rats was progressively elevated according to the duration of diabetes. TSP-1 expression was increased in BRECs incubated with high glucose at 48 hours. Moreover, high glucose also increased ERK1/2 expression, which peaked at 30 minutes and then decreased in the following 48 hours.</p><p><b>CONCLUSION</b>An elevation of TAAs/AA is associated with high glucose-induced nitrative stress, which probably involves upregulation of TSP-1 through activating ERK1/2.</p>


Subject(s)
Animals , Cattle , Male , Rats , Arachidonic Acid , Metabolism , Blotting, Western , Cells, Cultured , Diabetes Mellitus, Experimental , Metabolism , Extracellular Signal-Regulated MAP Kinases , Metabolism , Gas Chromatography-Mass Spectrometry , Rats, Sprague-Dawley , Reactive Nitrogen Species , Metabolism , Streptozocin , Thrombospondin 1 , Genetics , Up-Regulation
7.
China Journal of Orthopaedics and Traumatology ; (12): 208-211, 2011.
Article in Chinese | WPRIM | ID: wpr-344648

ABSTRACT

<p><b>OBJECTIVE</b>To compare clinical effects of clavicular hook plate fixation, coracoid transplantation, and clavicular hook plate fixation combined with modified dynamic muscle transfer for the treatment of the complete acromioclavicular dislocation.</p><p><b>METHODS</b>From January 2006 to November 2009, 65 patients with sustained complete acrominoclavicular dislocation were treated with clavicular hook plate fixation, coracoid transplantation,and clavicular hook plate fixation combined with modified dynamic muscle transfer. All the patients were divided into three groups: 22 patients in group A were treated with clavicular hook plate fixation, including 17 males and 5 females, with an average age of (31.0 +/- 10.0) years; 21 patient in group B were treated with coracoid transplantation, including 16 males and 5 females,with an average age of (33.0 +/- 6.4) years; 22 patients in group C were treated with clavicular hook plate fixation combined with modified dynamic muscle transfer,including 18 males and 4 females, with an average age of (30.0 +/- 5.3) years. Postoperative functional recovery was evaluated by Karlsson criteria.</p><p><b>RESULTS</b>All the patients were followed up, and the duration ranged from half to three years (averaged 1.5 years). In group A, 8 patients got half re-dislocation, 2 patients got complete re-dislocation and arthritis of acromioclavicular joint after internal fixations removal, 1 patient had clavicular hook plate broken after operation. In group B, 7 patients got half re-dislocation, 1 patient got complete re-dislocation,and 5 patients had arthritis of acromioclavicular joint with acute pain and limited shoulder function after internal fixations removal. In group C,2 patients got half re-dislocation, no complete re-dislocation and arthritis of acromioclavicular joint occurred after internal fixations removal. According to Karlsson evaluation, in group A, 12 patients obtained an excellent result, 8 good and 2 poor; in group B, the data were 9, 7 and 5 respectively; in group C, they were 20, 2 and 0 respectively. There were remarkable differences of therapeutic effects between the clavicular hook plate fixation combined with modified dynamic muscle transfer and that with either of the former two treatment methods (P < 0.05).</p><p><b>CONCLUSION</b>Clavicular hook plate combined with modified dynamic muscle transfer is a reliable and good treatment for the complete acrominoclavicular dislocation, with advantages such as easy to handle,stable fixation and early exercise.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Acromioclavicular Joint , Diagnostic Imaging , Wounds and Injuries , General Surgery , Joint Dislocations , Diagnostic Imaging , General Surgery , Postoperative Complications , Tomography, X-Ray Computed , Treatment Outcome
8.
China Journal of Chinese Materia Medica ; (24): 2653-2657, 2008.
Article in Chinese | WPRIM | ID: wpr-324831

ABSTRACT

<p><b>OBJECTIVE</b>: To profile urinary metabolite variations from 1, 2-dimethylhydrazine (DMH)-induced precancerous colon rats, Jinfu Kang treated rats and healthy controls.</p><p><b>METHOD</b>We used ethyl chloroformate derivatization and gas chromatography-mass spectrometry (GC-MS) based metabonomic method to analyze rat urines.</p><p><b>RESULT</b>The time-dependent variations of metabolite profile showed a progressive deviation of the metabolism in the model group from the initial pattern over time and a systemic recovery of the metabolism in the treatment group, which is consistent with the histological results. The in-depth analysis indicated that the disorder of tricarboxylic acid cycle (TCA), tryptophan metabolism, polyamine metabolism and gut flora structure were associated with DMH intervention.</p><p><b>CONCLUSION</b>Metabolic study revealed that Jinfu Kang can effectively reverse metabolic departures in DMH-induced precancerous colon rat, which is consistent with pathological results.</p>


Subject(s)
Animals , Male , Rats , Colonic Neoplasms , Pathology , Colonic Polyps , Drug Therapy , Urine , Dimethylhydrazines , Pharmacology , Drugs, Chinese Herbal , Pharmacology , Gas Chromatography-Mass Spectrometry , Rats, Wistar
9.
Chinese Journal of Cardiology ; (12): 232-235, 2008.
Article in Chinese | WPRIM | ID: wpr-243808

ABSTRACT

<p><b>OBJECTIVE</b>To observe serum adiponectin, free fatty acid (FFA) profile and other glucose and lipid metabolic parameters in essential hypertensive patients with metabolic syndrome (HPMS) or without metabolic syndrome (HP).</p><p><b>METHODS</b>The serum adiponectin was measured with the radioimmunoassay, FFA profile measured with the gas chromatography and mass spectrometer in 72 HPMS, 56 HP and 43 normal control subjects.</p><p><b>RESULTS</b>Serum adiponectin were significantly lower in HPMS group than those in the HP and control group (P < 0.05 or P < 0.01). Serum total free fatty acid (TFA), unsaturated fatty acid (UFA, linoleic acid, oleic acid, arachidonic acid, docosahexaenoic acid, eicosatrienoic acid), polyunsaturated fatty acid (PUFA) and n6PUFA were significantly higher in HPMS group than those in the HP and control groups (P < 0.05 or P < 0.01). Adiponectin was negatively correlated with body mass index, waist circumferences, waist hip ratio, triglycerides (r = -0.222, -0.235, -0.179, -0.194, P < 0.01 or P < 0.05, respectively) and positively correlated with high-density lipoprotein cholesterol (r = 0.336, P < 0.01); TFA and PUFA were positively correlated with body mass index, waist circumferences, fasting blood glucose, mean arterial pressure (r = 0.241 and 0.280, 0.198 and 0.188, 0.226 and 0.298, 0.274 and 0.334, P < 0.01 or P < 0.05, respectively) in all subjects.</p><p><b>CONCLUSION</b>Our data suggest that changes in serum adiponectin, FFA and n6PUFA might promote the development of metabolic syndrome in essential hypertensive patients.</p>


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Adiponectin , Blood , Fatty Acids, Nonesterified , Blood , Hypertension , Blood , Epidemiology , Metabolic Syndrome , Blood , Epidemiology
10.
Chinese Journal of Integrated Traditional and Western Medicine ; (12): 901-904, 2007.
Article in Chinese | WPRIM | ID: wpr-245612

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect and mechanism of Kangxianling (KXL, a TCM herbal compound) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO).</p><p><b>METHODS</b>Eighteen male SD rats were randomly divided into 3 groups, 6 in each group, the sham operated group, the model group, and the KXL group. Renal interstitial fibrosis model was established in rats by UUO. After rats were raised for additional 14 days, their body weight, serum levels of creatinine (SCr) and blood urea nitrogen (BUN) were analyzed. Then rats were sacrificed, their renal pathology examined by HE staining and PASM staining; expressions of transforming growth factor-beta1 (TGF-beta1), hepatocyte growth factor (HGF) mRNA, and a-smooth muscle actin (alpha-SMA), TGF-beta1 receptor I (TbetaR I), TGF-beta1 receptor II (TbetaR II) and hepatocyte growth factor receptor (C-Met) protein in kidney tissue were determined by RT-PCR and Western blotting respectively.</p><p><b>RESULTS</b>SCr and BUN in the model group were significantly higher than those in the sham operated group (P <0.05). Expressions of TGF-beta1 mRNA and a-SMA, TbetaR I , TbetaR II and C-Met protein in kidney tissue in the model group significantly up-regulated and mRNA expression of HGF significantly down-regulated, and obvious hyperplasia of the base member of glomeruli was seen. After intervention with KXL, BUN content significantly lowered, alpha-SMA, TbetaR I and TbetaR II protein expression decreased and HGF mRNA expression up-regulated significantly in the treated group, with slight pathological changes only shown as mild hyperplasia of the base member of glomeruli and renal tubules.</p><p><b>CONCLUSION</b>KXL could inhibit the protein expressions of a-SMA, TbetaR I , TbetaR II and increase the mRNA expression of HGF, which is a protective factor against renal fibrosis. Therefore, it is effective in alleviating the renal interstitial fibrosis and improving the renal function in UUO rats.</p>


Subject(s)
Animals , Male , Rats , Blotting, Western , Drugs, Chinese Herbal , Therapeutic Uses , Fibrosis , Hepatocyte Growth Factor , Genetics , Kidney , Metabolism , Pathology , Nephritis, Interstitial , Pathology , Nephrosclerosis , Pathology , Phytotherapy , RNA, Messenger , Genetics , Random Allocation , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Ureteral Obstruction
11.
Chinese Journal of Integrated Traditional and Western Medicine ; (12): 205-208, 2004.
Article in Chinese | WPRIM | ID: wpr-320212

ABSTRACT

<p><b>OBJECTIVE</b>To study the therapeutic effect of Angelica Injection (AI) in treating acute cerebral infarction (ACI).</p><p><b>METHODS</b>One thousand four hundred and four patients, who were treated with AI (692 patients in Group A), compound salvia (390 patients in Group B) and low molecular dextran injection (322 patients in Group C) respectively. Indexes such as CT scanning on infarcted volume, scoring of clinical neuro-function deficit taking on the 1st, 3rd, 7th, 15th and 25th day, clinical therapeutic effectiveness evaluated by the end of the 2nd week and the improvement of Barthel index scores were observed.</p><p><b>RESULTS</b>The total effective rate in Group A, B and C was 78.7%, 63.6% and 59.3% respectively, that in Group A was significantly higher than in the other two groups (P < 0.05). The improvement of neuro-function deficit scores and Barthel scores in Group A were better than those in Group B and C (on the 25th day, P < 0.01), and the decrement of infarcted volume in Group A was larger than that in Group C (P < 0.01).</p><p><b>CONCLUSION</b>AI has evident therapeutic effect in treating ACI.</p>


Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Angelica sinensis , Chemistry , Cerebral Infarction , Drug Therapy , Drugs, Chinese Herbal , Infusions, Intravenous , Phytotherapy
12.
Chinese Journal of General Practitioners ; (6)2003.
Article in Chinese | WPRIM | ID: wpr-683074

ABSTRACT

Objective To explore the relationship between free fatty acid(FFA)composition and other glucose and lipid metabolic parameters in patients with metabolic syndrome(MS)in community. Methods Serum FFA profile was measured with gas chromatography and mass spectrometry in 158 patients with varied metabolic syndrome components(MSC),including 61 with MS and 97 at high-risk for MS,and 43 control subjects,with diagnostic criteria by the International Diabetes Federation(IDF).Results Patients with MS had higher parameters of polyunsaturated fatty acid(PUFA)and n6PUFA,as compared to the patients at high risk and normal subjects(P0.05). Among the high-risk group,those with diabetes had increased linoleic acid,n6PUFA and total fatty acid (TFA),and decreased saturated fatty acid(SFA)/TFA,as compared to those without diabetes(P

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