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Objective:To explore the potential mechanisms of anterior cingulate cortex (ACC) in modulating pain behavior and anxiety-like behavior of rats with chronic non-specific low back pain induced by nerve growth factor (NGF).Methods:Ninety-six male SPF grade SD rats aged 8 weeks were randomly divided into four groups according the random number table method: control group, model group, control+ D-2-amino-5-phosphonopentanoate (D-AP5) group (control+ D-AP5 group) and model+ D-AP5 group, with 24 rats in each group.Low back pain model of rat was established by injection of NGF into multifidus muscle (left side) of the low backs of rats(two times with a five-day interval). Five days after modeling, rats in model+ D-AP5 group and control+ D-AP5 group were injected with the N-methyl-D-aspartate (NMDA) receptor antagonist D-AP5(2 μg, 0.3 μL) at the right side of the ACC once a day for consecutive 3 days, and rats in control group and model group were injected with the same amount of 0.9% sodium chloride solution. Seven days after modeling, the pain threshold of rats was evaluated by mechanical stimulation test and hot and cold plate test.The anxiety-like behavior was tested by open field test.The density of glial fibrillary acidic protein (GFAP) positive cells and c-Fos(a kind of immediate early gene) positive cells of the spinal cord were observed by immunofluorescence. The expression of GFAP, c-Fos, phosphorylated-c-Jun N-terminal kinases (p-JNK), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-X-C motif) ligand 1 (CXCL-1) proteins in the L2 segment of the spinal cord were detected by Western blot. SPSS 23.0 software was used for statistical analysis. One-way ANOVA was used to analyze normal distribution measurement data for comparison among multiple groups, and Tukey test was used for further pairwise comparisons. The Kruakal-Wallis H test was used for non-normal distribution measurement data, and Mann-Whitney U test was used for further pairwise comparisons with Bonferroni-corrected P-values. Results:In the experiments measuring pressure pain threshold (PPT) and paw withdrawal threshold (PWT), there were statistically significant differences in the PPT and PWT of rats among the four groups ( F=53.498, 41.939, both P<0.001). Seven days after modeling, PPT ((418.5±46.9) g) and PWT ( (55.6±7.1) g) in the ipsilateral side of the rats in model+ D-AP5 group were higher than those in model group ((290.0±32.0) g, (30.5±7.5) g) (both P<0.001). In the open field test, there were statistically significant differences in percentage of the inner zone distance ( H=11.922, P<0.01) and the percentage of inner zone time ( H=21.614, P<0.001) of rats among the four groups. The percentage of inner zone time in model+ D-AP5 group was higher than that in model group (5.6(4.3, 7.9) %, 3.1(2.1, 3.8) %) ( P<0.01). The results of immunofluorescence showed that there were statistically significant differences in the density of GFAP positive cells and c-Fos positive cells at the ipsilateral side of the superficial laminae of rats among the four groups ( H=49.085, F=18.120, both P<0.001). The density of GFAP positive cells (34.3(21.1, 47.5) cells/mm 2) and c-Fos positive cells ((52.7±39.4) cells/mm 2) at the ipsilateral side of the superficial laminae in model+ D-AP5 group were less than those in model group (76.5(68.6, 94.9) cells/mm 2, (112.4±63.7) cells/mm 2) (both P<0.001). The Western blot results showed that there were statistically significant differences in the protein expression of GFAP, c-Fos, p-JNK, MCP-1 and CXCL-1 in the L2 segment of rats among the four groups ( F=49.413, 38.437, 41.867, 36.735, 130.951, all P<0.001). The protein expression of GFAP (1.7±0.5), c-Fos (1.1±0.1), p-JNK (1.7±0.3), MCP-1 (1.0±0.4) and CXCL-1 (0.8±0.1) in the L2 segment in model+ D-AP5 group were lower than those in model group ((4.3±0.7), (2.6±0.5), (2.8±0.4), (2.9±0.4), (3.5±0.4)) (all P<0.01). Conclusion:ACC modulates mechanical hyperalgesia and anxiety-like behavior in chronic non-specific low back pain rats, which might be associated with the involvement of spinal astrocytes, p-JNK signal pathway and chemokines such as MCP-1 and CXCL-1.
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Objective:To investigate the expression of serum uric acid and cystatin C in older adult patients with diastolic heart failure and their correlation with ventricular remodeling.Methods:The clinical data of 173 older adult patients with diastolic heart failure (patient group) and 144 older adult patients who had normal heart function (control group) who received treatment in Liaoning Jinqiu Hospital from January 2018 to January 2020 were retrospectively analyzed. Left ventricular end-diastolic diameter, left ventricular mass index, serum uric acid and cystatin C levels were compared between the two groups. These indices were also compared between patients with different classes of heart failure. Serum uric acid and cystatin C levels were correlated with left ventricular end-diastolic diameter and left ventricular mass index.Results:Left ventricular end-diastolic diameter, left ventricular mass index, and serum uric acid and cystatin C levels in the patient group were (46.82 ± 4.56) mm, (117.45 ± 24.51) g/m 2, (380.23 ± 115.85) μmol/L, (1.41 ± 0.51) mg/L, respectively, which were significantly higher than (45.8 ± 3.96) mm, (111.19 ± 19.30) g/m 2, (333.65 ± 89.02) μmol/L, (1.06 ± 0.34) mg/L, respectively in the control group ( t = 2.10, 2.48, 3.95, 7.02, all P < 0.05). Serum uric acid level in patients with class IV heart failure was (432.48 ± 157.64) μmol/L, which was significantly higher than (355.22 ± 106.56) μmol/L and (379.89 ± 93.43) μmol/L in patients with class II and class III heart failure ( F = 5.18, P < 0.05). Pearson correlation analysis showed that serum uric acid level was positively correlated with left ventricular end-diastolic diameter ( r = 0.17, P < 0.05) and left ventricular mass index ( r = 0.18, P < 0.05) in older adult patients with diastolic heart failure. Conclusion:Serum uric acid plays an important role in the occurrence and development of diastolic heart failure in older adults. Serum uric acid level can help measure the degree of ventricular remodeling to some extent.
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Objective:To investigate the changes of autonomic nervous active substances in myocardium of rats with acute high-level spinal cord injury.Methods:Twenty-four clean-level healthy adult male SD rats weighting 250-300 g for 8-10 weeks old were divided into control group ( n=6) and spinal cord injury group ( n=18) according to the random number table. The spinal cord injury group was subdivided at 4, 12 and 24 hours, with 6 rats at each time point. The high-level spinal cord injury model was established by the modified Allen′s weight-drop method, and the spinal cord was only exposed in control group. The postoperative performance and BBB score for limb movement were observed in each group. The myocardium of each group was resected and used to observe ultrastructure of myocardial cells under transmission electron microscope and detect protein and mRNA levels of tyrosine hydroxylase (TH), noradrenaline transporter (NET), acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) by Western blot and RT-PCR analysis. Results:Rats of control group showed normal limb motion after operation without significant change from the preoperation level, and mean BBB score was 21 points. Rats of spinal cord injury group showed significantly reduced activities and feeding, with flaccid paralysis of both lower limbs as well as no spontaneous excretion, and showed BBB score of 0 point at 4 hours and 12 hours after injury, which was increased slightly at 24 hours after injury, with the highest score for 1 point. The ultrastructure of myocardial cells showed no obvious abnormalities in control group, while different degrees of changes in spinal cord injury group. Compared with control group, Western blot analysis showed that protein levels of TH and NET were decreased, while AChE and ChAT were increased in spinal cord injury group ( P<0.05 or 0.01). Compared with control group, RT-PCR analysis showed that mRNA levels of TH and NET were decreased, while AChE and ChAT were increased in spinal cord injury group ( P<0.05 or 0.01). mRNA levels of TH and NET in spinal cord injury group at 24 hours after injury were significantly different from those at 4 hours and 12 hours after injury (all P<0.05). mRNA levels of ChAT in spinal cord injury group were statistically significant at 12 hours and 24 hours after injury from those at 4 hours after injury, with significant difference at 12 hours and 24 hours after injury (all P<0.05). Conclusion:Sympathetic nerve active substances TH and NET are down-regulated but vagal nerve active substances AChE and ChAT up-regulated in myocardium of rats with acute high-level spinal cord injury, which may be related to the relative excitation of the parasympathetic nerve blocking the sympathetic innervation of the higher center to the heart following high-level spinal cord injury.