Astragaloside IV Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway / 中国结合医学杂志

OBJECTIVE@#To evaluate the protective effects of Astragaloside IV (AST) in a rat model of myocardial injury induced by cecal ligation and puncture (CLP).@*METHODS@#The model of sepsis-induced cardiac dysfunction was induced by CLP. Using a random number table, 50 specific pathogen free grade of Sprague Dawley rats were randomized into 5 groups: the sham group (sham), the model group (CLP, 18 h/72 h) and AST group (18 h/72 h). Except the sham group, the rats in other groups received CLP surgery to induce sepsis. CLP groups received intragastric administration with normal saline after CLP. AST groups received intragastric administration with AST solution (40 mg/kg) once a day. The levels of inflammatory mediators and oxidative stress markers in the serum of the septic rats were determined via enzyme-linked immunosorbent assay (ELISA) at different time point, such as interleukin 6 (IL-6), IL-10, high mobility group box-1 protein B1 (HMGB-1), superoxide dismutase (SOD), and malondialdehyde (MDA). Cardiac function was determined by echocardiography. Moreover, changes in myocardial pathology were evaluated using hematoxylin and eosin staining. The levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were analysed to determine the status of CLP-induced myocardium. In addition, the apotosis of myocardial cells was analysed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), IκB kinase α (IKKα), nuclear factor kappa B p65 (NF-κB p65) were detected by Western blot analysis. Moreover, survival rate was investigated.@*RESULTS@#AST improved the survival rate of CLP-induced rats by up to 33.3% (P<0.05). The cardioprotective effect of AST was observed by increased ejection fraction, fractional shortening and left ventricular internal diameter in diastole respectively (P<0.01 or P<0.05). Subsequently, AST attenuated CLP-induced myocardial apoptosis and the ratio of Bcl-2/Bax in the myocardium, as well as the histological alterations of myocardium (P<0.01 or P<0.05); the generation of inflammatory cytokines (IL-6, IL-10, HMGB-1) and oxidative stress markers (SOD, MDA) in the serum was significantly alleviated (P<0.01 or P<0.05). On the other hand, AST markedly suppressed CLP-induced accumulation of IKK-α and NF-κB p65 subunit phosphorylation (P<0.01 or P<0.05).@*CONCLUSIONS@#AST plays a significant protective role in sepsis-induced cardiac dysfunction and survival outcome. The possible mechanism of cardioprotection is dependent on the activation of the IKK/NF-κB pathway in cardiomyocytes.

Intervention Effect of Dachuanxiong Fang Multi-component Preparation on Acute Migraine Rat Model by Urine Metabolomics / 中国实验方剂学杂志

Objective: To investigate the intervention effect of Dachuanxiong Fang multi-component preparation on acute migraine rats, in order to explore the possible mechanism by using urine metabolomics technology. Method: The forty SD rats were randomly divided into 5 groups (n=8), control group, model group, low-dose Dachuanxiong Fang multi-component preparation (DCXF) group (0.19 g·kg-1), medium-dose DCXF group (0.37 g·kg-1), and high-dose DCXF group (0.74 g·kg-1). Rats were subcutaneously injected with 10 mg·kg-1 nitroglycerin for modeling, and Dachuanxiong Fang multi-component preparation was administered through intragastric administration. After half an hour of administration, blood was collected from the abdominal aorta, and the content of 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), nitric oxide (NO), nitric oxide synthase (NOS), calcitonlin gene related peplide (CGRP), dopamine(DA) in plasma were determined by enzyme-linked immuno sorbent assay (ELISA) kits. The contents of 5-HT and NOS in the hypothalamus and brainstem of the control group and the model group were analyzed, and the average optical density value was used for statistical analysis. UPLC-TOF/MS combined with principal component analysis (PCA) analysis was used to analyze different groups of rats and discover differential metabolites. Differential metabolites were analyzed by MetaboAnalyst 3.0 software for possible metabolic pathways. Result: After modeling, compared with the control group, the content of neurotransmitters in the model group was significantly increased (PPPβ-hydroxybutyrate showed an upward trend. According to the metabolic pathway prediction study, metabolic pathways with a higher correlation were found to be alanine, aspartic acid and glutamate metabolism, propionic acid metabolism, nitrogen metabolism and tryptophan metabolism. Conclusion: The possible metabolism pathway of Dachuanxiong Fang multi-component preparation is mainly amino acid metabolism in urine, and kynurenine is also the product of tryptophan metabolism pathway. The kynurenine metabolic pathway is also one of the main pathways of tryptophan metabolism.

Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor β1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1 / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effect of curcumin on fibroblasts in rats with cardiac fibrosis.</p><p><b>METHODS</b>The rats were randomly divided into 4 groups (n=12 in each group): the normal control, isoproterenol (ISO), ISO combined with low-dose curcumin (ISO+Cur-L), and ISO combined with high-dose curcumin (ISO+Cur-H) groups. ISO+Cur-L and ISO+Cur-H groups were treated with curcumin (150 or 300 mg•kg•day) for 28 days. The primary culture of rat cardiac fibroblast was processed by trypsin digestion method in vitro. The 3rd to 5th generation were used for experiment. Western blot method was used to test the expression of collagen type I/III, α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to test the proliferation of fibroblast.</p><p><b>RESULT</b>Curcumin significantly decreased interstitial and perivascular myocardial collagen deposition and cardiac weight index with reducing protein expression of collagen type I/III in hearts (P<0.05). In addition, curcumin directly inhibited angiotensin (Ang) II-induced fibroblast proliferation and collagen type I/III expression in cardiac fibroblasts (P<0.05). Curcumin also inhibited fibrosis by inhibiting myofibroblast differentiation, decreased TGF-β1, MMP-9 and TIMP-1 expression (P<0.05) but had no effects on Smad3 in Ang II incubated cardiac fibroblasts.</p><p><b>CONCLUSIONS</b>Curcumin reduces cardiac fibrosis in rats and Ang II-induced fibroblast proliferation by inhibiting myofibroblast differentiation, decreasing collagen synthesis and accelerating collagen degradation through reduction of TGF-β1, MMPs/TIMPs. The present findings also provided novel insights into the role of curcumin as an antifibrotic agent for the treatment of cardiac fibrosis.</p>

Research Progress of the Relationship between the Expression of TAR DNA-binding Domain Protein 43 and Brain Injury / 法医学杂志

TAR DNA-binding domain protein 43 （TDP-43） is a highly conserved and widely expressed nuclear protein. Nowadays, the expression of TDP-43 can be found in most neurodegenerative diseases such as Alzheimer's disease, which makes it become a neurodegenerative disease associated marker protein. From the current research status at homeland and abroad, and around the relationship between the expression of TDP-43 and brain injury, this article emphatically probes into the specific expression and function of TDP-43 in acute and chronic brain injury based on the knowledge of its biological characteristics, which aims to explore the feasibility for determining the cause of death and the injury and disability situations by TDP-43 in forensic pathology.

Construction of Research-Oriented State Key Clinical Department by Highlighting the Characteris- tics and Advantages of Chinese Medicine / 中国中西医结合杂志

As the largest research-oriented specialty department in national traditional Chinese medicine hospitals, the Department of Critical Care Medicine in Guangdong Provincial Hospital of Chinese Medicine insists on the development mode combined with clinical medicine and scientific research. By taking clinical and basic researches for integrative medicine preventing and treating acute myocardial in-farction and sepsis as a breakthrough, authors explored key problems of Chinese medicine in improving the prognosis related diseases and patients' quality of life. In recent 3 years our department has successively become the principal unit of the national key specialties cooperative group of critical care medicine (awarded by State Administration of Traditional Chinese Medicine), the key clinical specialties (awarded by National Health and Family Planning Commission), and Guangzhou key laboratory construction unit, and achieved overall lap in clinical medical treatment, personnel training, scientific research, and social service.

Progress on Correlation between the Expression of CDK5 and Brain Injury Time / 法医学杂志

Cyclin-dependent kinase 5 (CDK5) is a member of cyclin-dependent kinase family, which does not directly regulate cell cycle. Through phosphorylation of target protein, CDK5 plays an irreplaceable role in the development, reparation and degeneration of neurons. Brain injury refers to the organic injury of brain tissue caused by external force hit on the head. Owing to the stress and repair system activated by our body itself after injury, various proteins and enzymes of the brain tissues are changed quantitatively, which can be used as indicators for estimating the time of injury. This review summarizes the progress on the distribution, the activity mechanism and the physiological effects of CDK5 after brain injury and its corresponding potential served as a marker for brain injury determination.

Progress on Hypoxic-ischemic Brain Damage Associated with CCR2 and CCL2 / 法医学杂志

Hypoxic-ischemic brain damage (HIBD) is referred to a common type of cerebral damage, which is caused by injury, leading to shallow bleeding in the cortex with intact cerebral pia mater. In recent years, studies show that a various kinds of immune cells and immune cellular factors are involved in the occurrence of HIBD. CC chemokine receptor 2 (CCR2) is a representative of CC chemokine receptor, and is widely distributed in cerebral neuron, astrocyte, and microglial cells, and is the main chemo-tactic factor receptor in brain tissue. CC chemokine ligand 2 (CCL2) is a kind of basophilic protein and the ligand of CCR2, and plays an important role in inflammation. In order to provide evidence for correlational studies in HIBD, this review will introduce the biological characteristics of CCR2 and CCL2, and illustrate the relationship between the immunoreactivity and HIBD.

Comparative study on mathematical set-based drug release kinetics method and Kalman filter method applied in evaluating drug release of multi-component traditional Chinese medicine preparations / 中国中药杂志

<p><b>OBJECTIVE</b>To provide a mathematical set-based method for evaluating drug release kinetics of multi-component traditional Chinese medicine preparations.</p><p><b>METHOD</b>With Fuzheng Huayu prescription as the study model, a mathematical set-based method for evaluating drug release kinetics was established to guide the preparation of drug release system of Fuzheng Huayu prescription, and a quantitative evaluation was made for its multi-component drug release characteristics. Its accuracy was verified by Kalman filtering method.</p><p><b>RESULT</b>The comparison between the two showed that the sample No. 4 of Fuzheng Huayu drug release system showed synchronized drug release with its reference preparation Fuzheng Huayu capsules.</p><p><b>CONCLUSION</b>The results verified the accuracy and rationality of the evaluation method based on mathematics set. Meanwhile, it displayed the release of target preparations according to asynchronous coefficient (k) and other parameters, and found the orientation of regulating and improving the unit drug release dosage from relevant error parameters of various characteristic peak information, in order to purposefully regulate relevant components, and enable target preparations to meet the synchronized drug release requirements of the reference preparation. Meanwhile, it provided an effective measure for evaluating the quantitative characterization and synchronized release behavior of multi-component traditional Chinese medicines.</p>

Endogenous nitric oxide mediates lipoteichoic acid induced preconditioning on reoxygenation injury of cultured human coronary artery endothelial cells / 药学学报

<p><b>AIM</b>To explore the effects of lipoteichoic acid (LTA) induced delayed preconditioning (PC) on hypoxia-reoxygenation (H/R) injury of cultured human coronary artery endothelial cells (HCAECs), and to investigate the potential role of endogenous nitric oxide (NO) participated in the protective mechanism.</p><p><b>METHODS</b>HCAECs were incubated for 2 h in a hypoxic atmosphere and reoxygenated for 4 h in a normoxic atmosphere. The delayed PC was induced by pretreatment with LTA (30 or 300 microg x L(-1)) for 4 h before 24 h recovery. The extent of cellular injury after reoxygenation was assessed by the percentage of cellular injury with Trypan blue exclusion and by the amount of lactate dehydrogenase (LDH) in culture media. The NO level of the culture media was measured spectrophotometrically. Furthermore, HCAECs were exposed to 300 microg x L(-1) of LTA for 4 h, and to detect the expression of eNOS mRNA by RT-PCR method after cells were recovered from different points.</p><p><b>RESULTS</b>LTA pretreatment significantly decreased the percentage of the killed cell and the concentration of LDH in media. Also, LTA pretreatment obviously raised the concentrations of NO in culture media. The protective effects of LTA were abrogated by pretreatment with N-monomethyl-L-arginine (L-NMMA). Moreover, the expression of eNOS mRNA was significantly upregulated after HCAECs exposure to LTA for 4 h following 2 h or 4 h recovery.</p><p><b>CONCLUSION</b>LTA could induce the delayed protection against H/R induced endothelial injury and dysfunction of cultured HCAECs. NO produced by eNOS acts initially as a trigger and subsequently as a mediator of delayed PC.</p>