ABSTRACT
Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.
ABSTRACT
Drug-associated reward memories are conducive to intense craving and often trigger relapse. Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive. Here, we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm. We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference (CPP) without affecting CPP acquisition. Specifically, only simvastatin administered during extinction prevented cocaine-primed reinstatement. Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin. The metabolism of fatty-acids, phospholipids, and triacylglycerol was profoundly affected. Simvastatin reversed most of the effects on phospholipids induced by cocaine. The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions. Furthermore, simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine. In summary, pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.
Subject(s)
Animals , Male , Mice , Brain , Cocaine , Conditioning, Operant , Extinction, Psychological , Lipidomics , Simvastatin/therapeutic useABSTRACT
Objective To study the expression of vascular endothelial cell growth factor (VEGF) and its receptor 2 (VEGFR2) and apoptosis in the epididymis of rats with chronic arsenic poisoning.Methods Forty male Sprague-Dawley rats,weighting 160-200 g,were selected and randomly divided into four groups:high dose [60.0 mg/L sodium arsenite (NaAsO2)],medium dose (12.0 mg/L NaAsO2),low dose arsenic infected groups (2.4 mg/L NaAsO2),and control group (distilled water).The rats were treated with arsenic through drinking water for 6 consecutive months.At the end of the experiment,all rats were killed and epididymis was separated rapidly,apoptosis cells of rat epididymis were determined via the TUNEL method,the expressions of VEGF and VEGFR2 were observed through immunohistochemistry.Results The apoptosis of the epididymis tubules epithelial cells were compared in control,low,medium,and high dose groups (124.68 ± 6.59,138.96 ± 8.48,152.59 ± 10.79,170.69 ±16.60),the differences were statistically significant (F =10.562,P ＜ 0.05),with increased exposure doses of arsenic,apoptosis cells were increased.VEGF expression levels of the body,head and tail in epididymis were compared in control,low,medium,and high dose groups (148.50 ± 0.60,134.20 ± 0.85,98.23 ± 0.80;136.70 ± 0.95,128.20 ±0.72,90.30 ± 0.12;127.80 ± 0.62,117.60 ± 0.72,84.51 ± 0.60;120.26 ± 0.46,90.12 ± 0.36,66.43 ± 0.90),the differences were statistically significant (F =46.445,45.867,41.381,P ＜ 0.05),and VEGF expression levels in arsenic infected groups were lower than that in control group (P ＜ 0.05);VEGFR2 expression levels of the head and tail (130.70 ± 0.89,128.80 ± 0.70;126.30 ± 0.65,121.42 ± 0.62;120.26 ± 0.12,117.84 ± 0.55;102.60 ±0.78,104.92 ± 1.15) were compared,the differences were statistically significant (F =3.452,2.701,P ＜ 0.05),and VEGFR2 expression levels in arsenic infected groups were lower than that in control group (P ＜ 0.05).Conclusion Arsenism has inhibitory effect on the expression of VEGF and VEGFR2 in the epididymis,leading to epididymis epithelial cell apoptosis,which indicates it may play an important role in male infertility.
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Objective@#To analyze the clinical effect of standardized endoscopic esophageal variceal ligation alone or in combination with tissue adhesive injection for gastric varices (GV) after the first cirrhotic esophageal variceal bleeding.@*Methods@#A total of 97 patients who underwent a successful endoscopic therapy in our hospital due to the first cirrhotic esophageal variceal bleeding were enrolled, and according to the subsequent therapeutic regimen, they were divided into control group (48 patients) and treatment group (49 patients). The patients in the control group were given conservative treatment alone, and those in the treatment group were given endoscopic therapy regularly. The therapeutic regimen, changes in varices, complications, and death caused by rebleeding were compared between the two groups. The t-test was used for comparison of continuous data between groups, and the chi-square test or Fisher’s exact test was used for comparison of categorical data between groups.@*Results@#The treatment group achieved a remission rate of esophageal varices (EV) of 100% and a GV elimination rate of 93.75% after 2-3 times of endoscopic therapy; the EV recurrence, rebleeding, and mortality rates were 2.04%, 0, and 0, respectively, within 1 month, 16.33%, 4.08%, and 0, respectively, within 12 months, and 20.40%, 14.29%, and 4.08%, respectively, within 20 months; the incidence rate of gastric variceal bleeding (GVB) was 0. In the control group, the EV recurrence, rebleeding, and mortality rates were 4.17%, 2.08%, and 2.08%, respectively, within 1 month, 41.67%, 33.33%, and 8.33%, respectively, within 12 months, and 72.92%, 56.25%, and 20.83%, respectively, within 20 months; the incidence rate of GVB was 18.75%. There were significant differences between the two groups in the incidence rate of GVB (χ 2 = 13.605, P = 0.001) and EV long-term recurrence, rebleeding, and mortality rates (12 months: χ 2 = 16.326, P < 0.01; 20 months: χ 2 = 27.144, P < 0.01).@*Conclusion@#Gastroscopy and continuous endoscopic therapy for 2-3 times should be performed regularly after the first cirrhotic esophageal variceal bleeding to alleviate EV, eliminate GV, and reduce rebleeding and mortality rates.
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Objective To observe the thyroid hormone (TH) changes in patients with acute cerebral infarction in acute phase and convalescence,and to explore its clinical value.Methods Fifty cases of acute cerebral infarction patients from March 2015 to May 2016 in Heilongjiang Provincial Hospital were selected as observation group,at the same time 30 cases of healthy check-up people as control group.Serum levels of triiodothyronine (T3),thyroxine (T4),free triiodothyronine (FT3),free thyroxine (FT4) and thyroid stimulating hormone (TSH) were measured in 50 cases of acute cerebral infarction patients on the 2nd day (acute phase) and the 14th day (recovery) after onset of the disease,by using chemiluminescence method,and 30 cases of people underwent healthy physical check-up were treated the same way.Neurological injury and recovery of patients with cerebral infarction were evaluated using NIHSS.According to the recovery level of FT3,patients with cerebral infarction were divided into low FT3 group (FT3 ＜ 3.10 pmol/L) and normal FT3 group (FT3 ≥ 3.10 pmol/L).Prognosis of the patients was judged according to the NIHSS scores 90 days after discharged from the hospital,and NIHSS score improving acuity of 2 was judged as good prognosis.Results The T3 and FT3 levels in patients with acute cerebral infarction were significantly lower than those of people underwent healthy physical examination,the differences were statistically significant [(0.68 ± 0.22) vs(1.82 ± 0.31) nmol/L,(2.08 ± 0.31) vs (4.19 ± 0.75) pmol/L,all P ＜ 0.05].The T4,FT4 and TSH levels in patients with acute cerebral infarction were increased significantly,the differences were statistically significant [(142.56 ± 20.78) vs (109.89 ± 12.37) nmol/L,(12.88 ± 1.15) vs (9.77 ± 0.96) pmol/L,(5.15 ± 1.16) vs (2.95 ± 1.31) mU/L,all P ＜ 0.05].Compared with the acute phase,convalescence of cerebral infarction patients' serum T3 and FT3 levels [(1.75 ± 0.19) nmol/L,(3.97 ± 0.61) pmol/L] increased significantly,the differences were statistically significant (all P ＜ 0.05),and T4,FT4 and TSH [(115.64 ± 14.38) nmol/L,(10.05 ± 1.02) pmol/L,(3.16 ± 0.98) mU/L] obviously decreased,the differences were statistically significant (all P ＜ 0.05).Compared with control group,convalescence of cerebral infarction patients' serum T3,T4,FT3,FT4 and TSH were not statistically different (all P ＞ 0.05).There was a negative correlation between FT3 levels and NIHSS scores on admission (r =-0.586,P ＜ 0.05).Ninety days after discharge,7 cases (38.89％) of the patients had a good prognosis in low FT3 group,and normal FT3 group had 22 cases (68.75％) of patients with good prognosis,and the difference was statistically significant (x2 =7.186,P ＜ 0.05).Conclusions The thyroid hormone has a protective stress reaction in patients with acute cerebral infarction.The thyroid hormone level has changed significantly in the acute phase,and returned to normal level with improvement of the patients.As a biochemical indicator thyroid hormone detection can be used to estimate the prognosis of patients with acute cerebral infarction.
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AIM:To investigate the effects of P34H gene silencing on the expression of P34H and activity of hyaluronidase (HYD) in mouse sperm.METHODS:The recombinant plasmid series of P34H targeted short hairpin RNA (shRNA) were constructed by GV248 plasmids vector.These recombinant plasmids were transformed into DH 5αcompetent cells, and the plasmids were taken from DNA sequencing analysis .The HEK293T cells were co-transfected with shRNA and lentiviral packaging plasmids .The 3 kinds of recombinant lentiviruses and negative control lentiviruses were used to in -ject into the mouse epididymis and the expression of P 34H at mRNA and protein levels was detected by real-time PCR and Western blot, respectively.The location of P34H protein on the mouse spermatozoa was determined by indirect immunofluo-rescent staining using P34H antibody.The positive rate and activity intensity of HYD was detected by modified sodium hya-luronate-gelatin membrane.RESULTS:DNA sequencing analysis confirmed that the 3 P34H-shRNA sequences were suc-cessfully inserted into the lentiviral vectors .P34H expression in epididymis tissue was significantly decreased at both mR-NA and protein levels compared with those of the non-transfected and normal control vectors (P<0.05).The GV-P34H-shRNA-1 played a significant role in reducing the percentage of P 34H positive rate and the activity of HYD in mouse sperm.The silencing effect did not significantly differ between the non-transfected and normal control vectors .CONCLU-SION:Silencing of P34H significantly inhibits the percentage of P 34H positive rate and the activity of hyaluronidase in mouse sperm.
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@#Objective To explore an effective pulmonary function training health education approach for patients after cardiothoracic surgery. Methods 100 patients after cardiothoracic surgery were randomly divided into experimental group (50 cases) and control group (50 cases). The patients in the control group were given conventional health education, while those in the experimental group were given standard pulmonary function training health education approach. Their incidence of complications, duration of chesttube and hospitalization were compared. Results The incidence of complications, duration of chesttube and hospitalization were all less in the experimental group than the controls （P<0.05）. Conclusion Standard pulmonary function training health education approach can accelerate the recovery of patients after cardiothoracic surgery.