RESUMO
ObjectiveTo investigate the protective effect of Zhuangtongyin on the Middle Cerebral Artery Occlusion （MCAO） model by modulating ferroptosis through the Nrf2-SCL7A11/xCT-Gpx4 pathway and its underlying mechanism. MethodsC57BL/6J mice were randomly divided into Sham operation group （Sham）， model group （MCAO）， low-dose Zhuangtongyin group （ZTY-L）， high-dose Zhuangtongyin group（ZTY-H）， with 5 mice in each group. The MCAO group was modelled by silica gel embolization， the middle cerebral artery of mice was embolized for 1h， then the silica gel was pulled out and reperfusion was performed after 72 h； and the other operations in the Sham group were the same as those in the MCAO group except that the thread plug was not inserted. The neural function of mice was evaluated by Zea-Longa method. TTC staining was used to evaluate the volume of cerebral infarction. The level of brain injury was evaluated by HE staining and Nissl staining. Prussian blue staining and the expression of iron transport-related carrier receptors TfR1 and DMT1 on mRNA level was detected by qPCR to evaluate the iron ion deposition level in mice brain. The expression of lipid peroxidation-related gene ACSL4 on mRNA level was detected by qPCR， and the content of 4-HNE was detected by ELISA kit to evaluate the lipid peroxidation level of mice brain. The expressions of ferroptosis marker PTGS2 mRNA level was detected by qPCR. The expressions of Nrf2， SCL7A11/xCT， Gpx4 in mice brain tissue were detected by Western-blot and immunofluorescence. ResultsZhuangtongyin improved the nerve function of mice after MCAO （P＜0.05） and the cerebral infarction volume of mice （P＜0.05） and alleviate the pathological injury of cerebral cortex cells after MCAO operation. Zhuangtongyin attenuated the accumulation of trivalent iron ions in the brain tissue of mice following MCAO. Additionally， Zhuangtongyin downregulated the expression of TfR1 and DMT1 mRNA （P＜0.001）， a transporter associated with cellular iron ion uptake， in the brains of post-MCAO mice. Furthermore， Zhuangtongyin reduced levels of lipid peroxidation product 4-HNE （P＜0.001） and suppressed ACSL4 mRNA expression in brain tissue post-MCAO （P＜0.001）. Besides， Zhuangtongyin downregulated the expression of PTGS2 mRNA （P＜0.001）， in the brains of post-MCAO mice. Zhuangtongyin increased the expression of nrf2 into the nucleus （P＜0.001）， and increased the expression of xCT and Gpx4 in neurons after MCAO （P＜0.001）. ConclusionZhuangtongyin can enhance the nerve function and reduce cerebral infarction volume in MCAO/R mice， alleviate the pathological damage of cerebral cortex cells， and modulate the expression of key signaling molecules in the Nrf2-SCL7A11/xCT-Gpx4 pathway. Therefore， it is suggested that the mechanism by which Zhuangtongyin improves MCAO/R injury in mice may involve regulating ferroptosis through the Nrf2-SCL7A11/xCT-GPX4 pathway.
RESUMO
Objective To observe the clinical effect of Yi'naokang Capsules combined with Donepezil Hydrochloride Tablets in treating post-stroke cognitive impairment(PSCI).Methods 110 patients who met the diagnostic criteria of PSCI in the outpatient department were included.According to the random number table method,the patients were divided into trial group and control group,with 55 cases in each group.Patients in control group were treated with routine western medicine,including the treatment of Donepezil Hydrochloride Tablets and secondary prevention of stroke such as lowering blood pressure,lowering blood lipid,lowering blood glucose and anti-platelet aggregation.The trial group was treated with Yi'naokang Capsules on the basis of the treatment in control group,and both groups were treated for 6 months.Before and after 6 months of treatment,the cognitive function of patients was evaluated by the Montreal Cognitive Assessment(MoCA)scale.The activity of daily living(ADL)scale was used to evaluate the ability of daily living,and the severity of cerebral white matter lesions was evaluated by Fazekas scale,and the adverse reactions were also observed.Results After 6 months of treatment,the total score of the MoCA,the scores of visual space and executive function,attention,delayed recall and the ADL of the two groups were all improved(P＜0.05),and the improvement degree of the trial group was better than that of the control group(P＜0.05).The Fazekas score of the trial group after treatment was no significant difference when compared with that before treatment(P＞0.05),but it increased in the control group after treatment(P＜0.05),and the effect of delaying white matter lesion in the trial group was better than that in the control group(P＜0.05).Conclusion Yi'naokang Capsules combined with Donepezil Hydrochloride Tablets are superior to Donepezil alone in the treatment of PSCI,which can safely and effectively improve the cognitive function and daily living ability of patients,as well as prolong the progress of white matter lesions.
RESUMO
Objective:To evaluate the relationship between hippocampal miR-3065-5p and insulin-like growth factor-1/phosphatidylinositol 3-kinase/protein kinase B(IGF-1/PI3K/Akt)signaling pathway in a mouse model of perioperative neurocognitive disorder (PND).Methods:Eighty clean-grade healthy male C75BL/6 mice, aged 12-14 weeks, weighing 20-30 g, were divided them into 4 groups ( n=20 each) using the random number table method: control group (C group), PND group, miR-3065-5p agonist group (Ag group) and miR-3065-5p agonist negative control group (Ag-NC group). PND model was prepared by internal fixation of tibial fracture under anesthesia with 1.5% isoflurane. Two days before developing the model, miR-3065-5p agomir 2 μl was injected into the lateral ventricle in Ag group, miR-3065-5p agomir negative control 2 μl was injected into the lateral ventricle in Ag-NC group. Morris water maze test and open field test were performed at 7 days after surgery. The mice were sacrificed after the end of test, and hippocampal tissues were obtained for determination of the expression of miR-3065-5p, IGF-1 mRNA and Bcl-2 mRNA (by quantitative real-time polymerase chain reaction) and expression of IGF-1, phosphorylated Akt (p-Akt), phosphorylated glycogen synthase kinase-3β (p-GSK3β) and Bcl-2 (by Western blot). Results:There was no significant difference in each parameter in the open field test among the four groups ( P>0.05). Compared with group C, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in the other three groups ( P<0.05). Compared with PND group and Ag-NC group, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in Ag group ( P<0.05). Conclusions:Up-regulation of miR-3065-5p can inhibit the activation of IGF-1/PI3K/Akt signaling pathway, which might be one of the mechanisms of PND developed in mice.
RESUMO
Primary angle-closure glaucoma (PACG) is still one of the common blinding eye diseases in China.Because of the irreversibility of the vision loss it caused, the factors affecting the early development of glaucoma are of great concern.The understanding of static anatomic structure of high-risk anterior segment, such as shallow anterior chamber, short axial length, thick iris and large anterior lens cannot fully explain the transformation process of PACG, so the specific role of dynamic changes in the development of glaucoma should be further considered.This article expounded the differences in iris volume and dynamic process of elasticity between normal people and patients with PACG, the incoordination between lens and intraocular structure during eyeball development, the dynamic block and expansion of ciliary body, vitreous and choroid, and the latest research on the relationship between the abnormal ocular nerve and vascular system adjustment and change with the onset of PACG, in order to provide guidance for understanding the pathogenesis of PACG, accurate clinical diagnosis and formulation of treatment strategies.
RESUMO
Objective To evaluate the effect of electro-acupuncture preconditioning on the expression of protein kinase R-like endoplasmic reticulum kinase (PERK) in the hippocampus of mice following cerebral ischemia-reperfusion (I/R).Methods A total of 120 healthy male C56BL/6 mice,aged 7 weeks,weighing 20-30 g,were divided into 3 groups (n=40 each) using a random number table method:sham operation group (group S),cerebral I/R group (group I/R) and electro-acupuncture preconditioning group (group EA).Cerebral I/R was induced by clamping bilateral common carotid arteries for 15min followed by restoring cerebral blood flow in anesthetized mice.Dazhui and Baihui acupoints were stimulated with disperse-dense waves of 1 mA for 30 min once a day,lasting for 5 consecutive days,and cerebral I/R model was established at 24 h after the last stimulation in group EA.Animals were sacrificed at 24and 48 h of reperfusion,brains were removed,and hippocampi were isolated for determination of apoptotic neurons in hippocampal CAl region (by TUNEL) and expression of PERK (by Western blot).Results Compared with group S,the neurological deficit score and the number of apoptotic neurons in hippocampal CAl region were significantly increased at each time point of reperfusion in I/R and EA groups (P＜0.05).Compared with group I/R,the neurological deficit score and the number of apoptotic neurons in hippocampal CAl region were significantly decreased at each time point of reperfusion in group EA (P＜0.05).Conclusion The mechanism by which electro-acupuncture preconditioning mitigates endoplasmic reticulum stress during cerebral I/R may be related to inhibiting PERK activity in mice.
RESUMO
OBJECTIVE@#To investigate the expression of the cell division- associated gene NUF2 in breast cancer and its clinical significance.@*METHODS@#The expression of NUF2 in breast cancer tissues was analyzed using Oncomine database. The relationship between the expression of NUF2 and the prognosis of breast cancer was analyzed using the Kaplan-Meier Plotter database. Gene set enrichment analysis (GSEA) and GEO database were used to investigate the effect of NUF2 on gene enrichment. The String database was utilized to analyze the proteins associated with NUF2. The TIMER database was analyzed to assess the correlations of NUF2 with BUB1, MAD2L1 and MYC. The expressions of NUF2 mRNA in 8 pairs of breast cancer tissues and adjacent tissues were verified by q-PCR.@*RESULTS@#Compared with that in normal breast tissue, NUF2 was significantly overexpressed in breast cancer ( < 0.001). The overall survival time (HR = 1.52, = 0.015) and the recurrence-free survival time (HR = 1.85, = 3.2e-14) of the patients with high NUF2 expression were significantly shorter than those of patients with low NUF2 expression. In patients with high NUF2 expression, the enriched genes were involved mainly in cell cycle, P53, G2/M, DNA repair, MYC, and PI3K-AKT-MTOR signaling pathways, which were associated with tumor proliferation, invasion, metastasis and stemness. Combination of the results of String database, gene enrichment and TIMER database analyses suggested that NUF2 interacted directly with BUB1, MAD2L1, and MYC, which could promote the progression of breast cancer. The results of q-PCR showed that NUF2 expression was up-regulated in 6 cancer tissues and down-regulated in 2 cancer tissues.@*CONCLUSIONS@#NUF2 gene is overexpressed in breast cancer, and its expression level is important in predicting the prognosis of breast cancer.
Assuntos
Humanos , Neoplasias da Mama , Metabolismo , Proteínas de Ciclo Celular , Metabolismo , Regulação Neoplásica da Expressão Gênica , Fosfatidilinositol 3-Quinases , PrognósticoRESUMO
Objective:To observe the protective effect of deproteinized extract of calf blood (DECB)on the ethanol-induced liver injury of the mice,and to preliminaryly discuss its mechanism. Methods:Sixty healthy ICR mice were divided into control group,model group,positive drug group,low,medium and high doses of DECB groups (n=10).By intragastric administration,the mice in control group were given 20 mL·kg-1 saline solution, the mice in low,medium and high doses of DECB groups were administrated with 0.125,0.250,0.500 g·kg -1 DECB,and the mice in positive drug group were administrated with 0.63 g·kg -1 Hugan Tablets;once a day for 30 d. 1 h after the last administration,except control group,the mice in other groups were administrated with one-time grant of 50% ethanol 14 mL·kg -1 ,and fasted for 16 h to establish the models of acute alcohol liver injury.The endurance alcohol time and drunk time of the mice were determined,the activities of aspartate aminotransferase (ALT)and alanine transaminase (AST)activity in serum of the mice were detected,the levels of triglyceride (TG),glutathione (GSH)and malonic dialdehyde (MDA)in liver tissue were determined,and the pathological changes of liver tissue were detected.Results:Compared with model group,the drunk symptoms of the mice in different doses of DECB groups were obviously reduced,the endurance time of the mice in high dose of DECB group and positive drug group was prolonged (P <0.05),and the drinking time was shortened (P <0.05);the ALT and AST activities in serum in mediun and high doses of DECB groups were significantly lower than those in model group (P <0.05).Compared with model group,the MDA and TG levels in liver tissue of the mice in medium and high doses of DECB groups and positive drug group were obviously reduced,and the GSH levels were increased (P <0.05);compared with model group,the pathological damages of liver tissue of the mice in high dose of DECB group caused by ethanol were significantly reduced.Conclusion:DECB can improve ethanol-induced liver injury which may be related to the inhibition of hepatic oxidative stress response.
RESUMO
Objective To explore the effect of minimally invasive percutaneous plate osteosynthesis (MIPPO) operation in the treatment of Pilon type Ⅲ fractures.Methods 54 patients were randomly divided into 2 groups by visiting sequence with random number,odd into the observation group,even into the control group.The observation group(28 cases) received MIPPO operation treatment,the control group(26 cases) was treated with fixed operation.The efficacy was compared between the two groups.Results The excellent and good rate was 85.7％ in the observation group,which was 76.9％ in the control group,there was significant difference between the two groups (Ridit z =12.658,P =0.000).In the observation group,the callus time was (8.1 ± 1.6) w,fracture healing time was (6.5 ± 1.2) m,no refracture occurred; in control group,the callus time was (9.4 ± 2.1) w,the fracture healing time was (7.1 ± 1.1)m,1 case occurred refracture,the differences of callus and bone healing time between the two groups were statistically significant (t =7.865,8.632,all P ＜ 0.05).Conclusion MIPPO operation in the treatment of Pilon type Ⅲ fracture has good effect,MIPPO can be used and promoted in the Pilon type Ⅲ fracture.
RESUMO
Objective To observe the effect of metformin and exercise therapy for IGT. Methods 86 patients with IGT were given metformin and exercise therapy,the range of glucose,BMI and symptoms improvement were observed before and after the therapy. Results After 6 months therapy,the fasting blood glucose and 2 h after oral administration of 75 g glucose levels were significantly reduced(P＜0.01＝,BMI reduced(P＜0.05＝.72 cases (83.7%)were back to normal glucose tolerance,14 cases maintained IGT(those unable to adhere to exercise and no diet controlled),0 case became DM. Conclusion Metformin and exercise therapy had good efficacy in curing IGT.
RESUMO
Objective To observe the therapeutic effect of Qiliqiangxin capsule combined on refractory heart failure.Methods 60 patients with refractory heart failure were randomly recruited into a control group and a therapeutic group. The control group received the conventional treatment, and the therapeutic group took Qiliqiangxin capsule on the base of the conventional treatment (3 times a day, 4 granules/each time) combined with 120 mg cAMP meglumine. Treatment in both group lasted 14 days. Results: After the treatment, the therapeutic group showed improvement in the symptoms of heart failure. Comparing with the control group, the difference was significant (P＜0.05). Conclusion The therapeutic effect of Qiliqiangxin capsule combined on refractory heart failure is satisfied and can improve the quality obviously.
RESUMO
Objective: To observe the protective effects of Yougui drink(右归饮) on chronic renal failure rats with insufficiency of kidney-Yang(肾阳虚) and investigate its mechanisms.Methods: Chronic(renal) failure model with insufficiency of kidney-Yang was replicated by nephrectomy(5/6 renal cortex) and(propylthiouracil)(PTU) infused into the stomach.The model rats were randomly divided into three(groups:)(model) group,Yougui drink group and sham-operated group.Yougui drink group was given Yougui drink(infused) into stomach daily,while the other two groups were given equivalent water daily for 28 days.The(pathological) study of the kidney tissue was performed and the serum blood urea nitrogen(BUN),creatinine(Cr) and lipid levels were determined after the experiment.Results: Yougui drink significantly decreased serum BUN and Cr levels and increased the reduced triglycerides(TG) in the rats compared to model group(BUN:(13.65?1.37)mmol/L vs.(15.88?1.16) mmol/L,P
RESUMO
BACKGROUND: Growth-associated protein-43, a kind of protein relatedto axonal growth, plays a key role in promoting neural development, axonalregeneration, synaptic growth and structural and functional reconstructionand so on. In the study, we find that cyclovirobuxine D can protect braininjury in rats with experimental cerebral ischemia reperfusion.OBJECTIVE: To observe the effect of cyclovirobuxine D on the expression of growth-associated protein-43 mRNA in hypertensive rats with cerebral ischemia reperfusion.DESIGN: A randomized controlled animal experiment.SETTING: Foshan Hospital of Traditional Chinese Medicine of Guangdong Province; Central Laboratory of Guangdong Hospital of Traditional Chinese Medicine.MATERIALS: Cyclovirobuxine D is alkaloid monomer extracted from Chinese herb buxine. Cyclovirobuxine D powder with national protected traditional medicine number of ZYB20796057 was provided by Nanjing Xiaoyingyao Pharmaceutical Factory. Totally 120 two-to-three-month-old healthy male SD rats, of either gender, with body mass of 90 to 120 g, were used in this experiment.METHODS: This experiment was carried out in Foshan Hospital of Tra ditional Chinese Medicine of Guangdong Province and at the Central Laboratory of Guangdong Hospital of Traditional Chinese Medicine between June 2005 and March 2006. ①Stroke-prone-renovascular-hypertensive-rats models (RHRSP)were created by bilaterally narrowing the renal artery with silk loop clips. Totally 120 rats were randomly divided into blank group (n=20,renovascular hypertensive rats were given no treatments), sham operation group (n=20, rats were given only surgical trauma), model group (n=40, rats were given treatment of cerebral ischemia reperfusion) and cyclovirobuxine D-treated group (n=40, rats were given cyclovirobuxine D).② Unilateral occlusion of the middle cerebral artery ischemia reperfusion models were made with suture-occluded method. 6.48 mg/kg cyclovirobuxine D diluted by 1.5 mL normal saline was intraperitoneally injected into the rats of cyclovirobuxine D-treated group, twice per day; Normal saline was isochronously intraperitoneally injected into the rats of each subgroup of control group, 2 mL once, the method was the same as that of the cyclovirobuxine D-treated group; interval of injection time was 7 hours in each group. Rats in each group were executed on days 1, 7, 14 and 30after ischemia reperfusion. ③ Brain slice was prepared. The expression of growth-associated protein-43 mRNA of rats in each group was detected with in situ hybridization.MAIN OUTCOME MEASURES: ① The expression of growth-associated protein-43 mRNA around ischemia are following ischemia reperfusion for 2 hours. ②The expression of growth-associated protein-43 mRNA in hippocampus following ischemia reperfusion for 2 hours RESULTS: All the 120 rats entered the stage of result analysis. ① Immune in situ hybridization of growth-associated protein-43 mRNA: In situhybridization showed that expression of growth-associated protein-43 mRNA and expression of growth-associated protein-43 mRNA could be detected respectively in the hippocampus and marginal area of hematoma after ischemia and reperfusion.②The expression of growth-associated protein-43RNA around haematoma following cerebral ischemia reperfusion group as not found in blank group and sham-operation group; The expression of growth-associated protein-43 mRNA was found in the marginal zones around haematoma of rats in the model group on the 1st day following ischemia reperfusion and it was significantly increased on the 7th day, gradually reduced on the 14th day and still expressed on the 30th day but less,with significant difference at each time point (P ＜ 0.01); Expression of growth-associated protein-43 mRNA around haematoma at each time point was more in the cyclovirobuxine D-treated group than in the model group ,with significant difference (P ＜ 0.05). ③There was no significant difference of the expression of growth-associated protein-43 mRNA in hippocampus of rats following cerebral ischemia reperfusion between blank group and sham-operation group; Expression of growth-associated protein-43 mRNA was found in hippocampus of rats in the model group on the 1st day after modeling, and it reached the peak on the 7th day, gradually decreased on the 14th day and significantly decreased on the 30th day, but significantly more than that of sham-operation group; The expression of growth-associated protein-43 mRNA in hippocampus was significantly more at each time point in cyclovirobuxine D-treated group than in model group, with significant difference (P ＜ 0.01).CONCLUSION: Cyclovirobuxine D up-regulates the expression of growthassociated protein-43 mRNA after reperfusion and promotes axonal regeneration of rats with experimental cerebral ischemia.
RESUMO
0.05). However, in the presence of 16.5 mmol/L glucose, PGF_ 2? increased significantly in insulin secretion (P
RESUMO
OBJECTIVE:To establish an HPLC method for content determination of isoniazid and isonicotinic acid in isoniazid tablets.METHODS:The determination was performed on SHIM-PACK VP-ODS C18 column.The mobile phase consisted of methanol-water(0.2% docusate sodium,40 :60) at a flow rate of 0.8 mL?min-1.The UV detection wavelength was set at 261 nm and the sample size was 5 ?L.RESULTS:The linear range was 10～1000 ?g?mL-1 for isoniazid(r=0.999 8) with average recovery of 99.57%(RSD=0.26%) and 2～24 ?g?mL-1 for isonicotinic acid(r=0.9994) with average recovery of 98.96%(RSD=0.96%).The limited quantities were 0.05 ?g?mL-1,0.16 ?g?mL-1,respectively.CONCLUSION:The established method is simple,rapid and accurate,and suitable for content determination of isoniazid tablets.
RESUMO
AIM: To study the preventive effects of Keningfang decoction on the experimental influenza virus pneumonia in mice and its mechanism. METHODS: Fifty NIH mice were divided into five groups randomly (ten mice in each group), normal control group, model group, virazole treatment group, Keningfang I treatment group, Keningfang II treatment group. The FM 1 virus strain that kept in frozen condition were revived and cultured in chick embryo. The mice in every group that were lightly anesthetized by aether, and infected by dropping FM 1 15 LD 50 into the nose, except for the normal control group, by equal volume distilled water. Mice were treated with drugs or distilled water two days before the model was made (0 3 mL, 2 times a day). The mice were treated with drug for six days, then was killed, the lungs were collected, and kept in -70 ℃. HSP70 was measured in the lung tissue by Western blot. Pathologic changes of the mice lungs were observed under microscope. RESULTS: Compared with the normal control group, HSP70 in the other groups were increased significantly (P
RESUMO
Objective To investigate the expression of nestin protein and insulin-like growth factor 1(IGF-1) mRNA in rat brain injured by ischemia-reperfusion(I/R),and observe the effects of Tongxinluo,one of Chinese herb drugs,on the expression.Methods The rat model of cerebral I/R injury,reproduced by middle cerebral artery occlusion(MCAO) and release,were divided into three groups: high-dose Tongxinluo group(given 1g/kg?d of Tongxinluo],low-dose Tongxinluo group(given 0.5g/kg?d of Tongxinluo) and control group(administration of saline).2ml of Tongxinluo or saline each time was administered to each rat and 2 times every day up to day 3,5,7,14,21 and 30 after the injury.The expression of nestin in the subventricular zone(SVZ) and hippocampal dentate gyrus zone(DG) was detected by immunohistochemistry,and the IGF-1 mRNA expression around ischemic area was detected by RT-PCR.Results Compared with the control group,the immunofluorescence magnitude of nestin-positive neurons in SVZ and DG was significantly higher in high-and low-dose Tongxinluo groups(P0.05).Conclusions Tongxinluo,a kind of Chinese herb drugs,may promote the proliferation of neural stem cells in SVZ and DG after cerebral I/R injury in rats,and the mechanism may be related to upregulation of IGF-1 mRNA induced by Tongxinluo.