1.Mechanisms of Fufang Biejia Ruangan Pills Against Alcoholic Liver Disease via Regulating Liver-brain Dialogue Mediated by HMGB1-BDNF Axis
Yudong LIU ; Xiangying YAN ; Tao LI ; Chu ZHANG ; Bingbing CAI ; Zhaochen MA ; Na LIN ; Yanqiong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):214-223
ObjectiveTo systematically and objectively characterize the pharmacological effects of Fufang Biejia Ruangan pills (FBRP) in the intervention of alcoholic liver disease (ALD) using acute and chronic ALD mouse models and to elucidate its molecular mechanisms. MethodFifty SPF-grade male BALB/c mice were randomly divided into the normal group, model group, and FBRP low-, medium-, and high-dose groups (9.6, 19.2, 38.4 mg·kg-1). Except for the normal group, the remaining groups were given 56° white wine by gavage to establish the acute ALD model, with samples collected after 4 weeks. Thirty SPF-grade male C57BL/6N mice were randomly divided into the normal group, model group, and FBRP medium-dose group (19.2 mg·kg-1). The chronic ALD mouse model was established using the Lieber-DeCarli method over a 10-week period. Inflammatory markers in liver tissues were assessed using hematoxylin-eosin (HE), Sirius Red, oil red O staining, and enzyme-linked immunosorbent assay (ELISA). Intoxication behaviors of each group were objectively evaluated through sobering-up time, net-catching, and pole-climbing tests. Further bioinformatics analyses based on clinical transcriptomic data were conducted to identify key targets and molecular mechanisms of FBRP in alleviating ALD through liver-brain dialogue, with experimental validation by ELISA, Western blot, and immunohistochemical staining. ResultCompared with the normal group, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in liver tissues of mice in the acute and chronic ALD model groups were significantly increased (P<0.05). Compared with the model group, the levels of AST and ALT in liver tissue of mice in FBRP groups were significantly decreased (P<0.05). Compared with the normal group, the time of grasping the net and climbing the pole in the acute ALD model group was significantly decreased within 4 weeks (P<0.01). Compared with the model group, the grasping and climbing time of FBRP high dose groups increased significantly within 4 weeks (P<0.05). Compared with the normal group, the expression of high mobility group protein B1 (HMGB1) protein in liver tissue and prefrontal lobe tissue of mice in the chronic ALD model group was significantly increased (P<0.01). Compared with the model group, the expression of HMGB1 protein in FBRP medium dose group was significantly decreased (P<0.05,P<0.01). Compared with the normal group, the expression of brain-derived neurotrophic factor (BDNF) protein and the release of γ-aminobutyric acid (GABA) in the prefrontal cortex of the model group were significantly decreased (P<0.01). Compared with the model group, the expression of BDNF protein and the release of GABA in the FBRP medium dose group were significantly increased (P<0.05). ConclusionThis study revealed that FBRP improved key pathological changes in ALD by modulating liver-brain dialogue mediated by the HMGB1-BDNF axis. These findings provide experimental evidence for the clinical use of FBRP in treating ALD and offer new insights for the development of ALD therapeutic agents.
2.Identification of Pharmacodynamic Material Basis of Ruyi Zhenbaowan by Multidimensional Correlation Model of "Pharmacodynamic-target-component-pharmacokinetic"
Mingzhu XU ; Huaiping LI ; Zhaochen MA ; Tao LI ; Yudong LIU ; Ziqing XIAO ; Chu ZHANG ; Kedian CHEN ; Weihua MA ; Feng HUANG ; Na LIN ; Yanqiong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):68-77
ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2, and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them, and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that, plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points, and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry(UPLC-Q-TRAP/MS), and drug concentration-time curves were plotted, then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network, a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes, such as estrogen receptor 1(ESR1), cyclic adenosine monophosphate(cAMP)-dependent protein kinase catalytic subunit alpha(PRKACA) and protein kinase B1 (Akt1), and 10 corresponding potential effect components, such as glycyrrhizic acid and betulinic acid, were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components, gallic acid, apigenin-7-O-glucuronide, glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid, with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic, this study analyzes the main effective materials of Ruyi Zhenbaowan, such as glycyrrhizic acid, gallic acid, apigenin-7-O-glucuronide and apigenin, which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.
3.Identification of in Vitro and in vivo Chemical Constituents of Ruyi Zhenbaowan Based on UHPLC-Q Exactive Orbitrap HRMS
Kedian CHEN ; Zhaochen MA ; Bingbing CAI ; Ying LIU ; Yudong LIU ; Tao LI ; Mingzhu XU ; Haiping WANG ; Na LIN ; Yanqiong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):78-84
ObjectiveTo identify the chemical constituents of Ruyi Zhenbaowan in vitro and in vivo. MethodThe chemical constituents of Ruyi Zhenbaowan were identified based on UHPLC-Q Exactive Orbitrap HRMS. A total of 12 male SD rats were randomized into two groups: control (pure water) and Ruyi Zhenbaowan (1.8 g·kg-1). The rats were administrated with the suspension of Ruyi Zhenbaowan or pure water by gavage. After 1.5 h, the plasma and cerebrospinal fluid were collected. Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 150 mm, 1.7 μm) with a mixture of 0.1% formic acid aqueous solution (A) and acetonitrile (B) as the mobile phase. Gradient elution was carried out according to the procedure of 0~15 min,97%~80%A;15~30 min ,80%~60%A;30~40 min,60%~30%A;40~45 min,30%~5%A. The ion source was electrospray ionization, and scan range was m/z 100-1 500. The prototype components and the components in the plasma and cerebrospinal fluid were analyzed qualitatively by scanning in positive and negative ion modes and identified by comparison with the data in published literature and the information of standard substances. ResultA total of 126 chemical constituents were identified from the 80% methanol solution of Ruyi Zhenbaowan, and 14 and 7 prototype constituents were detected in the plasma and the cerebrospinal fluid, respectively. In addition, the fragmentation rules of apigenin, apigenin-7-O-glucuronide, galangin, liquiritin, piperine, glycyrrhizic acid, eugenol, gallic acid, and cholic acid were deduced. ConclusionThis study achieved rapid multicomponent characterization and identification of Ruyi Zhenbaowan in vitro and in vivo, providing theoretical support for exploring active substances and performing quality control.l.
4.Establishment and evaluation of the comorbidity animal model of knee osteoarthritis and hypertension with pattern of liver and kidney deficiency
Zhaochen MA ; Chu ZHANG ; Mingzhu XU ; Yudong LIU ; Weiheng CHEN ; Yanqiong ZHANG ; Na LIN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(5):652-661
Objective To establish the animal model of comorbidity of knee osteoarthritis(KOA)and hypertension with pattern of liver and kidney deficiency and evaluate its characteristics of comorbidity and pattern.Methods Wistar-Kyoto(WKY)rats and spontaneously hypertensive rats(SHR)were assigned to the WKY control group(control group),hypertension combined with KOA sham-operation group(sham-operation group),hypertension combined with KOA group(model group),hypertension combined with KOA and liver-kidney deficiency pattern group(LKD group).The animal model of KOA combined with hypertension was prepared by anterior cruciate ligament transection(ACLT)in spontaneously hypertensive rats.ACLT combined with intramuscular injection of hydrocortisone was performed to prepare an animal model of KOA with liver-kidney deficiency(LKD)pattern type,combined with hypertension.Then,the related indexes of LKD syndrome were detected in turn,including the contents of thyroid stimulating hormone(TSH),testosterone(T),corticosterone(CORT),adrenocorticotropic hormone(ACTH)in serum,and enzyme activities of alanine transaminase(ALT),aspartate transaminase(AST),and alkaline phosphatase(ALP)in serum,the mass ratio of liver,kidney,spleen,thymus to the brain,body weight,anal temperature,activity situation,and emotion.Systolic blood pressure,diastolic blood pressure,and other blood pressure-related indices were also detected.The levels of serum tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),plantar mechanical pain sensitivity threshold,weight difference score of both hind limbs,hind limb joint swelling,and quadruped gait parameters were also measured.Furthermore,hematoxylin-eosin,safranine-fast green,and Masson staining were performed to observe pathological changes,cartilage degeneration,and bone destruction of the knee joint,and the microstructure parameters of the tibia were detected by Micro-CT imaging.Results Compared to the model group,the contents of serum TSH,ACTH,T,CORT and the mass ratio of the kidney,spleen,and thymus to the brain in the LKD group decreased(P<0.05).Compared to the control group,the systolic blood pressure and diastolic blood pressure of the other three groups increased significantly(P<0.05).Compared to the sham-operation group,serum TNF-α and IL-1β levels increased,plantar mechanical pain threshold decreased,weight difference score of both hind limbs and joint swelling of the affected limb increased(P<0.05),and gait parameters(e.g.,gait length and standing time of the affected limbs)became abnormal in the model and LKD groups.Simultaneously,the cartilage surface defect of the rat knee joint was severe,the arrangement of the surface chondrocytes was altered,the cartilage layer became thinner,the muscle fibers increased,and the cartilage ossification was severe.Furthermore,the relative volume,thickness,and number of trabeculae of the knee joint decreased significantly(P<0.05).Conclusion The rat model established in this study is consistent with the clinical characteristics of integrated traditional Chinese and Western medicine in patients with comorbidities of hypertension and KOA with liver and kidney deficiency pattern.This rat model can characterize the typical symptoms of liver and kidney deficiency pattern.It has typical pathological changes in knee cartilage and subchondral bone tissues and can maintain a stable range of high systolic and diastolic blood pressure.It also explore the scientific connotation of simultaneous treatment of different diseases in traditional Chinese medicine,revealing the therapeutic mechanism and developing new drugs.
5.Analysis of risk factors of short-term prognosis in patients with severe Budd-Chiari syndrome
Zedong WANG ; Shuaibo LING ; Suxin LI ; Luhao LI ; Zhaochen LIU ; Dingyang LI ; Lin LI ; Yang YANG ; Shengyan LIU ; Xiaowei DANG
Chinese Journal of Surgery 2024;62(6):606-612
Objective:To explore the risk factors of short-term prognosis of severe Budd-Chiari syndrome (BCS) patients,established and verified the nomogram prediction model for these BCS patients and evaluated its clinical application value.Methods:This study is a retrospective cohort study. The clinical data of 171 patients with severe BCS diagnosed were retrospectively analyzed in the Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023. There were 105 males and 66 females, aged (52.1±12.8) years (range: 18 to 79 years). The patients were divided into two groups based on whether they died within 28 days: the death group ( n=38) and the survival group ( n=133). The risk factors for short-term death of patients were analyzed,and independent risk factors were screened by univariate and multivariate analysis. Furthermore,these factors were used to establish the nomogram prediction model. The area under the curve(AUC),the Bootstrap Resampling,the Hosmer-Lemeshow test and the Decision Curve Analysis(DCA) were used to verify the model′s differentiation,internal verification,calibration degree and clinical effectiveness,respectively. Results:Univariate and multivariate Logistics regression analysis showed that the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time were independent risk factors ( P<0.05). The above factors were used to successfully establish the prediction model with 0.908 of AUC and 0.895 of the internal verification of AUC,indicating that the predictive model was valuable. The 0.663 P-values in the Hosmer-Lemeshow test indicated the high calibration degree of the model. The clinical effectiveness of the model was proved by the 18% clinical benefit population using the DCA curve with the 17% probability threshold. Conclusions:The independent risk factors are the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time. An adequate basis was acquired by establishing a nomogram prediction model of the short-term prognosis of severe BCS,which was helpful for early clinical screening and identification of high-risk patients with severe BCS who could die in the short term and timely providing timely intervention measures for improving the prognosis.
6.Analysis of risk factors of short-term prognosis in patients with severe Budd-Chiari syndrome
Zedong WANG ; Shuaibo LING ; Suxin LI ; Luhao LI ; Zhaochen LIU ; Dingyang LI ; Lin LI ; Yang YANG ; Shengyan LIU ; Xiaowei DANG
Chinese Journal of Surgery 2024;62(6):606-612
Objective:To explore the risk factors of short-term prognosis of severe Budd-Chiari syndrome (BCS) patients,established and verified the nomogram prediction model for these BCS patients and evaluated its clinical application value.Methods:This study is a retrospective cohort study. The clinical data of 171 patients with severe BCS diagnosed were retrospectively analyzed in the Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023. There were 105 males and 66 females, aged (52.1±12.8) years (range: 18 to 79 years). The patients were divided into two groups based on whether they died within 28 days: the death group ( n=38) and the survival group ( n=133). The risk factors for short-term death of patients were analyzed,and independent risk factors were screened by univariate and multivariate analysis. Furthermore,these factors were used to establish the nomogram prediction model. The area under the curve(AUC),the Bootstrap Resampling,the Hosmer-Lemeshow test and the Decision Curve Analysis(DCA) were used to verify the model′s differentiation,internal verification,calibration degree and clinical effectiveness,respectively. Results:Univariate and multivariate Logistics regression analysis showed that the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time were independent risk factors ( P<0.05). The above factors were used to successfully establish the prediction model with 0.908 of AUC and 0.895 of the internal verification of AUC,indicating that the predictive model was valuable. The 0.663 P-values in the Hosmer-Lemeshow test indicated the high calibration degree of the model. The clinical effectiveness of the model was proved by the 18% clinical benefit population using the DCA curve with the 17% probability threshold. Conclusions:The independent risk factors are the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time. An adequate basis was acquired by establishing a nomogram prediction model of the short-term prognosis of severe BCS,which was helpful for early clinical screening and identification of high-risk patients with severe BCS who could die in the short term and timely providing timely intervention measures for improving the prognosis.
7.Predictive value of the Naples prognostic score for patients with intrahepatic cholangiocarcinoma after radical resection
Shuaibo LING ; Luhao LI ; Zhaochen LIU ; Suxin LI ; Lin LI ; Xiaowei DANG
Chinese Journal of Hepatobiliary Surgery 2024;30(8):586-591
Objective:To study the clinical value of the Naples prognostic score (NPS) in predicting the prognosis of patients with intrahepatic cholangiocarcinoma (ICC) after radical resection and establish a nomogram prediction model.Methods:Clinical data of 77 patients with ICC undergoing radical hepatectomy for the first time in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were retrospectively collected, including 46 males and 31 females, aged (58.9±11.0) years old. The area under the receiver operating characteristic curve for NPS to predict the death after radical hepatectomy in ICC patients was 0.673, and the optimal cut-off value for NPS based on the Youden's index was 2.5. According to the optimal cut-off value of NPS, patients were divided into two groups: the low NPS group (patients with NPS≤2.5, n=37) and high NPS group (patients with NPS>2.5, n=40). The clinicopathological data including resection extent, blood transfusion, tumor differentiation, lymphovascular invasion, lymph node metastasis and postoperative complications were compared between the groups. Follow-ups were conducted via outpatient or telephone reviews. Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival comparison. Cox proportional hazards regression was used to analyze the risk factors affecting postoperative survival. A prediction nomogram was established and evaluated. Results:Compared to the low NPS group, the proportion of patients with tumor length ≥5 cm, lymphovascular invasion, lymph node metastasis, tumor carbohydrate antigen 19-9 ≥37 U/ml and the level of neutrophil to lymphocyte ratio were increased in the high NPS group, while the proportion of patients with serum albumin ≥40 g/L was decreased (all P<0.05). The cumulative survival rate of patients in the high NPS group was lower than that of the low NPS group ( P=0.001). Multivariate Cox analysis showed that ICC patients with lymphovascular invasion, lymph node metastasis, and NPS>2.5 had a higher risk of short survival after surgery (all P<0.05). The nomogram model based on NPS has a good predictive capacity. Conclusion:High preoperative NPS score indicates poor postoperative prognosis, and NPS score is an independent risk factor affecting the prognosis of ICC patients.
8.Predictive value of controlled nutritional status score for overt hepatic encephalopathy after transjugular intrahepatic portosystemic stent-shunt of Budd-Chiari syndrome
Shengyan LIU ; Luhao LI ; Suxin LI ; Zhaochen LIU ; Dingyang LI ; Lin LI ; Jingju WANG ; Chengshuo RUAN ; Xiaowei DANG
Chinese Journal of Digestive Surgery 2023;22(2):260-267
Objective:To investigate the predictive value of controlled nutritional status (CONUT) score for overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosys-temic stent-shunt (TIPSS) in Budd-Chiari syndrome patients.Method:The retrospective case-control study was conducted. The clinicopathological data of 48 Budd-Chiari syndrome patients who underwent TIPSS in the First Affiliated Hospital of Zhengzhou University from August 2014 to March 2021 were collected. There were 26 males and 22 females, aged (46±13)years. Observation indicators: (1) surgical situations and follow-up; (2) analysis of influencing factors of OHE after TIPSS; (3) predic-tion of OHE after TIPSS. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was performed using the t test. Measurement data with skewed distribution were represented by M( Q1, Q3), and comparison between groups was performed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or Fisher exact probability. Multivariate analysis was performed using the Logistic regression model with forward method. The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to evaluate the efficacy. Comparison among AUC was performed using the Delong test. Results:(1) Surgical situations and follow-up. All 48 patients underwent TIPSS successfully, and the operation time of the 48 patients was (131±29)minutes. All patients were implanted with 8 mm covered stent. All 48 patients were followed up for 46(25,71)months, and there were 14 cases with OHE and 34 cases without OHE after TIPSS. Of the 14 cases with OHE, 12 cases were evaluated as West-Haven Ⅱ grade and 2 cases were evaluated as West-Haven Ⅲ grade. (2) Analysis of influencing factors of OHE after TIPSS. Results of multivariate analysis showed that history of hepatic encephalo-pathy and CONUT score were independent factors influencing the incidence of OHE of Budd-Chiari syndrome patients who underwent TIPSS ( odds ratio=8.36, 1.74, 95% confidence interval as 1.02?68.75, 1.12?2.69, P<0.05). (3) Prediction of OHE after TIPSS. Results of ROC curve showed that the AUC of the CONUT score, the Child-Pugh score of liver function and the integrated model of end-stage liver disease (iMELD) score in predicting the incidence of OHE after TIPSS was 0.77(95% confidence interval as 0.64?0.91, P<0.05), 0.71(95% confidence interval as 0.56?0.87, P<0.05) and 0.71(95% confidence interval as 0.53?0.88, P<0.05), respectively, and there was no significant difference between the AUC of the CONUT score and the Child-Pugh score of liver function or the iMELD score ( Z=0.84, 0.59, P>0.05). The optimal cutoff value of CONUT score in predicting the incidence of OHE after TIPSS was 7, with the sensitivity, specificity and Yodon index as 78.6%, 61.8% and 0.40, respectively. Conclusion:The CONUT score can be used to predict the incidence of OHE in Budd-Chiari syndrome patients who underwent TIPSS, and the discrimination of CONUT score is equivalent to the Child-Pugh score of liver function and the iMELD score.
9.Inhibitory effect of astaxanthin on oxidative stress damage in lens epithelial cells and its mechanism
Yong LI ; Zhaochen LIU ; Huacong PENG
Chinese Journal of Experimental Ophthalmology 2023;41(5):428-435
Objective:To investigate the regulatory effect of astaxanthin on oxidative stress injury induced by hydrogen peroxide (H 2O 2) in lens epithelial cells and its possible mechanism. Methods:The HLEB-3 cells were cultured with different concentrations (0, 50, 100, 200, 500, 750 μmol/L) of H 2O 2.The cell inhibition rate was detected by the methyl thiazolyl tetrazolium (MTT) method, and the 50%inhibiting concentration (IC50) was calculated.HLEB-3 cells were cultured with different concentrations (0, 5, 10, 20, 50 μmol/L) of astaxanthin.The cell survival rate was detected by the MTT method.HLEB-3 cells were divided into four groups for 24-hour culture, namely normal control group cultured with complete medium, oxidative stress group cultured with 250 μmol/L H 2O 2, 10 μmol/L astaxanthin group cultured with 10 μmol/L astaxanthin and 250 μmol/L H 2O 2, and 20 μmol/L astaxanthin group cultured with 20 μmol/L astaxanthin and 250 μmol/L H 2O 2.The cell apoptosis rate was determined by flow cytometry.The nitric oxide (NO) concentration, superoxide dismutase (SOD) activity, glutathione (GSH) activity and malondialdehyde (MDA) content were detected by ELISA.The protein expressions of nuclear factor erythroid-2 related factor 2 (Nrf2) in nuclei, cytoplasmic Nrf2, heme oxygenase-1 (HO-1) and NAD (P) H, quinine oxidoreductase 1 (NQO1) were detected by Western bolt.The cells were divided into four groups, namely normal control-small interfering RNA (NC-siRNA) group, Nrf2-siRNA group, NC-siRNA+ astaxanthin group and Nrf2-siRNA+ astaxanthin group.The cells were transfected with NC-siRNA or Nrf2-siRNA accordingly.The cells were co-cultured for 24 hours with 0/10 μmol/L astaxanthin and 250 μmol/L H 2O 2 24 hours after transfection, respectively.The cell apoptosis rate was determined by flow cytometry.The NO concentration, SOD activity, GSH activity and MDA content were detected by ELISA. Results:With the increase of H 2O 2 concentration, the inhibition rate of HLEB-3 cells increased.There were significant differences in the inhibition rate of HLEB-3 cells treated with different concentrations of H 2O 2 ( F=12.358, P<0.05). The IC50 value of H 2O 2 on HLEB-3 cells was 264.20 μmol/L.The survival rates of HLEB-3 cells treated with 0, 5, 10, 20 and 50 μmol/L astaxanthin were (100.00±0.00)%, (102.20±1.34)%, (109.50±3.60)%, (115.40±4.13)%, (93.60±2.59)%, respectively.Then 10 μmol/L and 20 μmol/L were chosen as the experimental dose.The cell apoptosis rate of oxidative stress group was (38.50±2.38)%, which was higher than (9.20±0.24)% of normal control group, with a statistically significant difference ( P<0.05). The cell apoptosis rate of 10 μmol/L astaxanthin group was (27.60±4.33)%, which was lower than (38.50±2.38)% of oxidative stress group, but higher than (14.90±1.23)% of 20 μmol/L astaxanthin group and (9.20±0.24)% of normal control group, showing statistically significant differences (all at P<0.05). The NO and MDA contents were higher and the SOD and GSH concentrations were lower in oxidative stress group than in normal control group, 10 μmol/L astaxanthin group and 20 μmol/L astaxanthin group, and the differences were statistically significant (all at P<0.05). The NO and MDA contents were higher and the SOD and GSH concentrations were lower in 10 μmol/L astaxanthin group than in normal control group and 20 μmol/L astaxanthin groups, and the differences were statistically significant (all at P<0.05). There were significant differences in the relative expression levels of nuclear Nrf2, cytoplasmic Nrf2, HO-1 and NQO1 proteins among normal control group, oxidative stress group, 10 μmol/L astaxanthin group and 20 μmol/L astaxanthin group ( F=43.512, 20.381, 31.014, 23.435; all at P<0.001). The relative expression of nuclear Nrf2 protein gradually decreased, and the relative expression of nuclear Nrf2, HO-1 and NQO1 proteins increased gradually in normal control group, oxidative stress group, 10 μmol/L astaxanthin group and 20 μmol/L astaxanthin group, and there were significant differences when compared in pairs (all at P<0.05). The apoptosis rates of Nrf2-siRNA group and Nrf2-siRNA+ astaxanthin group were higher than those of NC-siRNA group and NC-siRNA+ astaxanthin group, and the differences were statistically significant (all at P<0.05). The cell apoptosis rate was higher in NC-siRNA group than in NC-siRNA+ astaxanthin group, showing a statistically significant difference ( P<0.05). There was no significant difference in the apoptosis rate between Nrf2-siRNA+ astaxanthin group and Nrf2-siRNA group ( P>0.05). The NO and MDA concentrations were higher and the SOD and GSH activities were lower in Nrf2-siRNA group than in the NC-siRNA group, with statistically significant differences (all at P<0.05). The NO and MDA concentrations were lower and the SOD and GSH activities were higher in NC-siRNA+ astaxanthin group than in NC-siRNA group and Nrf2-siRNA+ astaxanthin group, and the differences were statistically significant (all at P<0.05). There was no significant difference in NO and MDA concentrations or the SOD and GSH activities between Nrf2-siRNA+ astaxanthin group and Nrf2-siRNA group (all at P>0.05). Conclusions:Astaxanthin enhances the resistance of lens epithelial cells to H 2O 2-induced oxidative stress damage, which may be achieved by activating the Nrf2-related signaling pathway.
10.The clinical effects of beprost sodium tablets combined with Epley repositioning maneuver in treatment of postrior semicircular canal benign paroxysmal positional vertigo
Wei JIA ; Xiaowei LIU ; Zhaochen LI
Journal of Apoplexy and Nervous Diseases 2022;39(9):813-817
To study the clinical effects of beprost sodium tablets combined with Epley manual reduction in treatment of benign paroxysmal positional vertigo(BPPV). Methods A total of 338 patients with posterior semicircular canal BPPV who were treated in the neurogy clinic of our hospital from January 2019 to December 2020 were enrolled in the study,who were randomly divided into the observation group,who were treated in Epley manual reduction combined with oral beprost sodium tablets,118 cases;control group 1,who were treated with only Epley manual reduction,114 cases and control group 2,who were treated with Epley manual reduction combined with oral betahistine mesilate tablets,106 cases. The clinical efficacy,vestibular symptom index(VSI),dizziness handicap inventory(DHI) and relapse rate were observed and compared between the three groups. Results The total effective rate in the observation group was 91.53%,which was significantly higher than that(73.68) in control group1 and(86.79%) in control group2,the difference was statistically significant(P<0.05). One week and one month After manual reduction,the vestibular symptom index(VSI) scores and the dizziness handicap inventory(DHI) scores in three group were significantly lower than pretreatment,moreover,the decrease degree in the observation group was more significant than the other two control groups,the difference was statistically significant(P<0.05). Within 3 months after treatment,the relapse rate in the observation group(18.64%)was lower than that in control group1(34.21%) and in control group2(27.36%),the difference was statistically significant(P<0.05). Conclusion The clinical effects of beprost sodium tablets combined with Epley manual reduction in treatment of posterior semicircular canal BPPV are superior to those by simple Epley manual reduction and by Epley manual reduction combined with betahistine mesilate.


Result Analysis
Print
Save
E-mail