ABSTRACT
Objective To investigate the effects of 5-hydroxy-1-methylhydantoin (HMH) on kidney injury induced by paraquat (PQ). Methods Fifteen SPF healthy Kunming mice were randomly divided into normal saline (NS) control group, PQ poisoning model group and HMH intervention group, with 5 mice in each group. PQ poisoning model was challenged by one-time gavage of 30 mg/kg PQ solution. The NS group received the same amount of NS by gavage. The HMH group was given 100 mg/kg of HMH immediately after the model was made and continued to be gavaged. Mice in each group were sacrificed 1 day after HMH gavage and heart blood and renal tissue were harvested for examination. The morphological changes of renal tissue were observed under light microscope by hematoxylin-eosin (HE) staining. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in renal tissue were detected according to the instructions of the kit. The expression of heme oxygenase-1 (HO-1) and interleukin-1β (IL-1β) in renal tissues were detected by Western Blot. The serum metabolites were detected by gas chromatography time-of-flight mass spectrometry (GC-TOF-MS), the overall distribution of each sample was observed by principal component analysis (PCA), the accuracy of the model was evaluated by multidimensional analysis orthogonal partial least squares-discriminant analysis (OPLS-DA), and the difference metabolites were screened by variable importance in the projection (VIP) value > 1. Results Light microscopic observation showed that: glomerular structure in NS group was clear, there was no hyperemia and inflammatory cell infiltration in renal interstitium and blood vessels. In PQ group, some glomeruli atrophy and necrosis, capillary congestion in glomeruli, infiltration of inflammatory cells around glomeruli, swelling of renal tubular epithelial cells, slight stenosis of lumen, and occasional necrosis and exfoliation of epithelial cells occurred. The degree of kidney injury in HMH group was significantly less than that in PQ group. Compared with the NS group, the content of MDA in the PQ group was significantly increased (nmol/g: 6.70±0.84 vs. 2.70±0.43, P < 0.01) and the activity of SOD was significantly decreased (kU/L: 33.30±4.66 vs. 50.20±3.23, P < 0.05), the protein expression of HO-1 and IL-1β were significantly increased (HO-1/β-actin: 1.11±0.12 vs. 0.61±0.13, IL-1β/β-actin: 0.93±0.13 vs. 0.32±0.06, both P < 0.05). Compared with the PQ group, the content of MDA in the HMH group was significantly decreased (nmol/g: 5.10±0.93 vs. 6.70±0.84, P < 0.05) and the activity of SOD was significantly increased (kU/L:61.00±9.02 vs. 33.30±4.66, P < 0.05), the protein expression of HO-1 was significantly decreased (HO-1/β-actin:0.77±0.07 vs. 1.11±0.12, P < 0.05), however, there was no significant difference in the protein expression of IL-1β (IL-1β/β-actin: 0.87±0.13 vs. 0.93±0.13, P > 0.05). Metabolite detection results showed that: compared with NS group, the levels of creatinine, glycine, succinic acid, fumaric acid and citric acid were significantly increased in the PQ group (VIP value was 1.50, 1.58, 1.64, 1.74 and 1.95 respectively, all P < 0.05), while the levels of palmitic acid, α-tocopherol and 6-phosphogluconic acid were significantly decreased (VIP value was 1.10, 1.55 and 1.56 respectively, all P < 0.05). Compared with the PQ group, the levels of creatinine and citric acid were significantly decreased in the HMH group (VIP value was 1.50 and 1.86, both P < 0.05), while trans-4-hydroxy-proline, D-glyceric acid, 2, 6-fructose phosphate, 6-phosphate gluconic acid and aminomalonic acid were significantly increased (VIP value was 1.36, 1.55, 1.63, 1.68 and 1.76 respectively, all P < 0.05). Conclusions HMH protects kidney injury caused by PQ poisoning by correcting tricarboxylic acids cycle disturbance, lipid peroxidation and energy metabolism disturbance, and its mechanism is related to the regulation of HO-1 protein expression through Nrf2 pathway.
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Objective T o observe the expression changes of hypoxia inducible factor-1α (H IF-1α) and vascular endothelial grow th factor-A (V E G F-A ) in rats w ith arrhythm ias, and to explore the differences of the expression pattern in the tw o indicators of acute m yocardial ischem ia caused by arrhythm ias and coronary insufficiency. Methods T he arrhythm ia w as induced by C aC l2, and the expression changes of H IF-1α and V E G F-A w ere detected by im m unohistochem istry, W estern blotting and real-tim e PC R w ithin 6 h after the arrhythm ia in rats. Results T he expression of H IF-1α and V E G F-A show ed diffuse in the m yocardial tissue of rats died from arrhythm ias. B oth of them increased in the early arrhythm ia, then decreased. E xtensive m yocardial ischem ia happened at the beginning of arrhythm ia occurrence and its range didn't expand w ith tim e. Conclusion T he expressions of H IF-1α and V E G F-A in m yocardium of the rats w ith arrhythm ia can provide evidence for the differential diagnosis of acute m yocardial is-chem ia caused by fatal arrhythm ia and coronary insufficiency.
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Brain natriuretic peptide (BNP), a natriuretic peptide hormone, is mainly secreted by cardiomyocytes when they are pulled by mechanical force. BNP acts to increase natriuresis and decrease vascular resistance, thereby decreasing blood volume, systemic blood pressure and afterload. It is not only the main indicators of cardiac function which is widely used in clinical, recent studies have also shown that it has a very important value in identifying sudden cardiac death(SCD). However, the exact expression of the regulation mechanism is still unknown. This paper reviewed the structure, expression of the regulation mechanism of BNP, and the application progress in clinical and forensic.
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MicroRNA (miRNA or miR) is a class of highly conserved endogenous non-coding RNA of 21~25nt, which is widely existed in organisms. Currently, miRNA has been proven to be associated with cardiovascular diseases in clinical research, but it has not been reported in the field of forensic medicine. This paper highlights recent findings about miRNA and its application in cardiovascular diseases, and the application aspect of miRNA in sudden cardiac death in forensic science.
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Objective To explore the changes of serum IgE and tryptase caused by anaphylactic shock rats and discuss the relation to PMI and preservative environm ent of corpse and specim en. Methods Rats were used for establishing anaphylactic shock m odels and random ly divided into room tem perature group, refrigeration group, frozen group, manual hem olysis group, specim en preservation group. And the control group was also established. The blood sam ples were collected after rats were sacrificed. The de-gree of hem olysis was graded according to the color of the upper layer of the serum . The mass concen-tration of IgE and tryptase in each group was detected by ELISA. Results The levels of serum IgE and tryptase in anaphylactic shock dead rats were higher than that of the control group. Room tem perature and frozen m ade obviously differences on the levels of serum IgE and tryptase with various PMI. The levels of serum IgE and tryptase in refrigeration group show ed relatively stable. The levels of serum tryptase and IgE were elevated with differently increasing hem olysis. The levels of serum IgE and tryptase show ed no obvious changes during the specim en kept under different tem perature conditions for 25 days. Conclusion Serum IgE and tryptase obviously increased in anaphylactic shock rats. H ow ever, the levels were influenced by PMI and environm ental tem perature, especially under the conditions of room tem perature and frozen.
ABSTRACT
Fatal anaphylactic shock is common in forensic practice. However, it is difficult to diagnose for lacking specific pathological and morphologic changes in forensic autopsy. The application of some biochemical indicators is of great significance. This paper reviews the biological characteristics of some biochemical indicators and detection methods. The forensic application, problems and prospects of these indicators are also introduced in details. The stable biochemical indicators, IgE, tryptase and chymase, show great potential and advantages in the identification of fatal anaphylactic shock in forensic medicine.