ABSTRACT
Objective:To evaluate the role of histone deacetylase 6 (HDAC6) in the maintanence of neuropathic pain (NP) and the relationship with myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway in the rats.Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-260 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), sham operation group (group S), NP group and NP plus HDAC6 inhibitor ACY-1215 group (group NP+ ACY). The rat model of NP was established by ligating the L 5 spinal nerve in anesthetized rats.The L 5 spinal nerve was only exposed without ligation in group S. In NP+ ACY group, ACY-1215 25 mg/kg was intraperitoneally injected daily for 21 days after the end of model establishing.The equal volume of solvent was intraperitoneally injected in S and NP groups, and group C was reared normally.The mechanical paw withdrawal threshold (MWT) was measured on 3 days before establishing the model (T 0), the day before establishing the model (T 1) and 1, 3, 7, 10, 14 and 21 days after establishing the model (T 2-7). The rats were sacrificed after measurement of MWT on day 21 after ligation, and the spinal dorsal horn tissues of L 4-6 were removed for determination of the expression of MyD88, NF-κB and phosphorylated NF-κB (p-NF-κB) (by Western blot) and expression of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) mRNA (by real-time polymerase chain reaction). Results:Compared with C and S groups, the MWT was significantly decreased at T 2-7, and the expression of MyD88, NF-κB, p-NF-κB, TNF-α mRNA and IL-1β mRNA was up-regulated in NP and NP+ ACY groups ( P<0.05). Compared with group NP, the MWT was significantly increased at T 5-7, and the expression of MyD88, NF-κB, p-NF-κB, TNF-α mRNA and IL-1β mRNA was down-regulated in group SNL+ ACY ( P<0.05). Conclusion:HDAC6 activation is involved in the maintanence of NP, which is related to activating MyD88/NF-κB signaling pathway in the rats.
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Objective:To evaluate the effect of valproic acid on the expression of M1/M2 microglia in the prefrontal cortex of rats with neuropathic pain (NP).Methods:Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 6-7 weeks, weighing 200-230 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (group S), group NP, and valproic acid group (group V). The NP model was established by ligation of the L 5 spinal nerve (SNL) of anesthetized rats.Valproic acid 300 mg/kg was intraperitoneally injected immediately after SNL and every day after ligation, once a day, for 3 consecutive days in group V, while the equal volume of normal saline was given instead of valproic acid in S and NP groups.The mechanical paw withdrawal threshold (MWT) was measured before ligation and at 1, 3, 7, 14, 21 and 28 days after ligation.Sucrose preference test and forced-swim test were performed on day 28 after ligation.After the end of the behavior test, the prefrontal cortex was removed for determination of the expression of cluster of differentiation (CD) 16 and CD206 by Western blot.The ratio of CD206/CD16 was calculated. Results:Compared with group S, the MWT at each time point after ligation and rate of preference for sucrose were significantly decreased, the duration of immobility in forced-swim test was prolonged, the expression of CD16 and CD206 was up-regulated, and the ratio of CD206/CD16 was decreased in group NP ( P<0.05). Compared with group NP, the MWT at each time point after ligation and rate of preference for sucrose were significantly increased, the duration of immobility in forced-swim test was shortened, the expression of CD16 was down-regulated, the expression of CD206 was up-regulated, and the ratio of CD206/CD16 was increased in group V ( P<0.05). Conclusion:The mechanism by which valproic acid improves depression may be related to promoting the expression of M2 microglia and inhibiting the expression of M1 microglia in the prefrontal cortex of rats with NP.
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Objective To evaluate the effect of activating adenosine A2A receptors on myocardial is-chemia-reperfusion ( I∕R) injury in diabetic rats and the relationship with autophagy. Methods Clean-grade healthy male Sprague-Dawley rats, aged 6 weeks, weighing 200-250 g, were studied. The diabetic rat model was established by intraperitoneal injection of 1％ streptozotocin 60 mg∕kg. Forty diabetic rats were divided into 4 groups ( n=10 each ) using a random number table method: sham operation group ( group Sham) , I∕R group ( group I∕R) , I∕R plus adenosine A2A receptor agonist CGS21680 group ( group CGS) , and I∕R plus CGS21680 plus adenosine A2A receptor antagonist ZM241385 group ( group CGS+ZM) . Myocardial I∕R was produced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120-min reperfusion. Adenosine A2A receptor agonist CGS2168010μg∕100g was in-travenously injected at 10 min before reperfusion in group CGS. CGS2168010 ug∕100g and ZM2413850. 2 mg∕kg were intravenously injected sequentially at 10 min before reperfusion in group CGS+ZM. Blood sam-ples were obtained at the end of reperfusion for determination of concentrations of creatine kinase-MB ( CK-MB), lactate dehydrogenase (LDH) and cardiac troponin I (cTnI) in serum (by enzyme-linked immu-nosorbent assay). The animals were sacrificed, and myocardial tissues were obtained for measurement of the percentage of myocardial infarct volume ( by TTC staining) and for determination of the expression of mi-crotubule-associated protein 1 light chain 3 Ⅰ ( LC3Ⅰ) , LC3 Ⅱ, p62 and Beclin-1 ( by Western blot) . LC3 Ⅱ∕LC3 Ⅰ ratio was calculated. Results Compared with group Sham, the serum CK-MB, LDH and cTnI concentrations and percentage of myocardial infarct volume were significantly increased, the expression of p62 and Beclin-1 was up-regulated, and the LC3Ⅱ∕LC3Ⅰratio was increased in group I∕R ( P<0. 05) . Compared with group I∕R, the concentrations of serum CK-MB, LDH and cTnI and percentage of myocardial infarct volume were significantly decreased, the expression of p62 and Beclin-1 was down-regulated, and the ratio of LC3Ⅱ∕LC3Ⅰwas increased in group CGS ( P<0. 05) , and no significant change was found in the pa-rameters mentioned above in group CGS+ZM (P>0. 05). Compared with group CGS, the concentrations of serum CK-MB, LDH and cTnI and percentage of myocardial infarct volume were significantly increased, the expression of p62 and Beclin-1 was down-regulated, and the ratio of LC3Ⅱ∕LC3Ⅰwas decreased in group CGS+ZM ( P<0. 05) . Conclusion Activating adenosine A2A receptors can mitigate myocardial I∕R injury, and the mechanism may be related to enhancing autophagy in diabetic rats.
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The paper quantizes symptom data through binary coding,divides 8 syndromes summed up by experts into excess and de-ficiency syndromes,values and quantizes them,and establishes the model for classification of excess and deficiency syndromes of colorec-tal cancer based on BP neural network and decision tree.The result shows that BP neural network classification model is more applicablefor the handling of the nonlinear mapping relation compared with decision tree classification model.