1.Exploration on the Potential Mechanism of Guben Zhike Pingchuan Granules in the Treatment of Cough-variant Asthma Based on Network Pharmacology and Experimental Validation
Yaqiao GONG ; Xingshi HUA ; Li MENG ; Xiaonan FANG ; Yu GAN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(9):31-39
Objective To explore the molecular mechanism of Guben Zhike Pingchuan Granules in treating cough variant asthma(CVA)through network pharmacology and molecular docking technology;To use CVA model rats for validation;To provide a basis for the basic research and clinical application of Guben Zhike Pingchuan Granules.Methods TCMSP and BATMAN-TCM databases were used to retrieve the active components and corresponding targets of Guben Zhike Pingchuan Granules,and CVA disease targets were screened using OMIM,GeneCards,DrugBank,PharmGKB databases to obtain drug disease intersection targets.Cytoscape 3.10.1 software was used to construct the drug-component-target network and screen the key components;STRING database was used to construct protein-protein interaction(PPI)network and screen core targets;GO and KEGG enrichment analysis was conducted using DAVID platform;AutoDock Vina software was used to conduct molecular docking on the core targets and key components with high degree value respectively.CVA rat model was established by smoking combined with intraperitoneal and subcutaneous multi-point injection of ovalbumin.The rats were randomly divided into blank group,model group,montelukast sodium tablets group,Guben Zhike Pingchuan Granules low-and high-dosage groups.The groups received corresponding medicine for 15 d.HE staining was used to observe the morphology of lung tissue;ELISA was used to detect the contents of serum interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α);immunohistochemistry was used to detect the positive expressions of AKT,EGFR and NFKB1 in lung tissue.Results A total of 9 996 active components and 1 119 potential targets of Guben Zhike Pingchuan Granules,2 740 CVA targets,467 drug and disease intersection targets were screened out;PPI network topology analysis showed that AKT1,STAT3,EGFR,NFKB1 and MTOR were the core targets;the results of enrichment analysis showed that Guben Zhike Pingchuan Granules played an anti-inflammatory role in the treatment of CVA mainly through the interaction of EGFR/PI3K-Akt/NF-κB signaling pathway;molecular docking showed good binding ability between the core targets and key components,with a binding energy of<-7.0 kcal/mol for EGFR and Quercetin.Animal experiment results showed that after intervention with Guben Zhike Pingchuan Granules,the alveolar walls of the lung tissue in the model rats narrowed,the size of the alveoli became uniform,lymphocyte infiltration improved significantly,bronchioles contracted,and mucus in the lumen decreased;compared with the model group,the serum contents of IL-1β and TNF-α decreased in Guben Zhike Pingchuan Granules low-and high-dosage groups and montelukast sodium tablets group,and the positive expressions of AKT,EGFR and NFKB1 in lung tissue decreased(P<0.05,P<0.01).Conclusion Guben Zhike Pingchuan Granules may mediate the inflammatory response through the EGFR/PI3K-Akt/NF-κB signaling pathway,significantly improve the structural damage of CVA lung tissue,inhibit inflammatory cell infiltration,down-regulate the expressions of inflammatory factors,and thus exert therapeutic effects on CVA.
2.Exploring schizophrenia pathogenesis and treatment from the perspective of spirit,soul,and inferior spirit
Yuling WANG ; Xiaonan XU ; Ting FANG ; Han XU ; Shuran ZHOU ; Xiangning CUI ; Jian WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1352-1357
Schizophrenia is a prevalent mental-behavioral disorder characterized by perceptual disturbances,affective dysregulation,and behavioral abnormalities.In traditional Chinese medicine,it is classified under"manic depressive psychosis"according to its symptomatology.The concepts of"spirit,soul,and inferior spirit"originate from Lingshu·Benshen.Drawing on the concept of"spirit governs the soul and inferior spirit"from Lei Jing,this study explored schizophrenia pathogenesis and treatment from the perspective of the three-level regulation of spirit,soul,and inferior spirit.The core pathogenesis involves failure of spirit to govern as the root cause,disruption of soul homing as the pathodynamic process,and the loss of inferior spirit's somatic functional expression as the manifestation.The pathological locations are the heart,liver,and lungs.Therapeutic strategies are developed according to the pathological transmission pattern"spirit derangement,soul floating,inferior spirit dissipation,"forming a treatment system that emphasizes"calming the heart and tranquillization,restoring its control to solidify the root;suppressing the liver soul and regulating the central mechanism to pacify excess to stop mania;purifying the lungs and calming the inferior spirit to restore its clarity and regulate sensory perception and restore cognition."The treatment emphasizes the synergistic use of"calming the spirit,stabilizing the soul,and soothing the inferior spirit,"and combines acupuncture and repetitive transcranial magnetic stimulation and other treatments to treat both the manifestation and root cause of schizophrenia.Exploring the syndrome differentiation and treatment of schizophrenia from the perspective of spirit,soul,and inferior spirit,aiming to provide a theoretical basis for the treatment of schizophrenia with traditional Chinese medicine.
3.Exploring schizophrenia pathogenesis and treatment from the perspective of spirit,soul,and inferior spirit
Yuling WANG ; Xiaonan XU ; Ting FANG ; Han XU ; Shuran ZHOU ; Xiangning CUI ; Jian WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1352-1357
Schizophrenia is a prevalent mental-behavioral disorder characterized by perceptual disturbances,affective dysregulation,and behavioral abnormalities.In traditional Chinese medicine,it is classified under"manic depressive psychosis"according to its symptomatology.The concepts of"spirit,soul,and inferior spirit"originate from Lingshu·Benshen.Drawing on the concept of"spirit governs the soul and inferior spirit"from Lei Jing,this study explored schizophrenia pathogenesis and treatment from the perspective of the three-level regulation of spirit,soul,and inferior spirit.The core pathogenesis involves failure of spirit to govern as the root cause,disruption of soul homing as the pathodynamic process,and the loss of inferior spirit's somatic functional expression as the manifestation.The pathological locations are the heart,liver,and lungs.Therapeutic strategies are developed according to the pathological transmission pattern"spirit derangement,soul floating,inferior spirit dissipation,"forming a treatment system that emphasizes"calming the heart and tranquillization,restoring its control to solidify the root;suppressing the liver soul and regulating the central mechanism to pacify excess to stop mania;purifying the lungs and calming the inferior spirit to restore its clarity and regulate sensory perception and restore cognition."The treatment emphasizes the synergistic use of"calming the spirit,stabilizing the soul,and soothing the inferior spirit,"and combines acupuncture and repetitive transcranial magnetic stimulation and other treatments to treat both the manifestation and root cause of schizophrenia.Exploring the syndrome differentiation and treatment of schizophrenia from the perspective of spirit,soul,and inferior spirit,aiming to provide a theoretical basis for the treatment of schizophrenia with traditional Chinese medicine.
4.Exploration on the Potential Mechanism of Guben Zhike Pingchuan Granules in the Treatment of Cough-variant Asthma Based on Network Pharmacology and Experimental Validation
Yaqiao GONG ; Xingshi HUA ; Li MENG ; Xiaonan FANG ; Yu GAN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(9):31-39
Objective To explore the molecular mechanism of Guben Zhike Pingchuan Granules in treating cough variant asthma(CVA)through network pharmacology and molecular docking technology;To use CVA model rats for validation;To provide a basis for the basic research and clinical application of Guben Zhike Pingchuan Granules.Methods TCMSP and BATMAN-TCM databases were used to retrieve the active components and corresponding targets of Guben Zhike Pingchuan Granules,and CVA disease targets were screened using OMIM,GeneCards,DrugBank,PharmGKB databases to obtain drug disease intersection targets.Cytoscape 3.10.1 software was used to construct the drug-component-target network and screen the key components;STRING database was used to construct protein-protein interaction(PPI)network and screen core targets;GO and KEGG enrichment analysis was conducted using DAVID platform;AutoDock Vina software was used to conduct molecular docking on the core targets and key components with high degree value respectively.CVA rat model was established by smoking combined with intraperitoneal and subcutaneous multi-point injection of ovalbumin.The rats were randomly divided into blank group,model group,montelukast sodium tablets group,Guben Zhike Pingchuan Granules low-and high-dosage groups.The groups received corresponding medicine for 15 d.HE staining was used to observe the morphology of lung tissue;ELISA was used to detect the contents of serum interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α);immunohistochemistry was used to detect the positive expressions of AKT,EGFR and NFKB1 in lung tissue.Results A total of 9 996 active components and 1 119 potential targets of Guben Zhike Pingchuan Granules,2 740 CVA targets,467 drug and disease intersection targets were screened out;PPI network topology analysis showed that AKT1,STAT3,EGFR,NFKB1 and MTOR were the core targets;the results of enrichment analysis showed that Guben Zhike Pingchuan Granules played an anti-inflammatory role in the treatment of CVA mainly through the interaction of EGFR/PI3K-Akt/NF-κB signaling pathway;molecular docking showed good binding ability between the core targets and key components,with a binding energy of<-7.0 kcal/mol for EGFR and Quercetin.Animal experiment results showed that after intervention with Guben Zhike Pingchuan Granules,the alveolar walls of the lung tissue in the model rats narrowed,the size of the alveoli became uniform,lymphocyte infiltration improved significantly,bronchioles contracted,and mucus in the lumen decreased;compared with the model group,the serum contents of IL-1β and TNF-α decreased in Guben Zhike Pingchuan Granules low-and high-dosage groups and montelukast sodium tablets group,and the positive expressions of AKT,EGFR and NFKB1 in lung tissue decreased(P<0.05,P<0.01).Conclusion Guben Zhike Pingchuan Granules may mediate the inflammatory response through the EGFR/PI3K-Akt/NF-κB signaling pathway,significantly improve the structural damage of CVA lung tissue,inhibit inflammatory cell infiltration,down-regulate the expressions of inflammatory factors,and thus exert therapeutic effects on CVA.
5.Characteristics, outcomes and its relative risk factors in elderly recipients of heart transplantation: a single-center experience
Shanshan ZHENG ; Zhe ZHENG ; Jie HUANG ; Zhongkai LIAO ; Lin ZHANG ; Xiaonan FANG ; Sheng LIU
Chinese Journal of Organ Transplantation 2024;45(3):167-174
Objective:To explore the trends and outcomes for heart transplantation (HT) in elderly recipients and further examine the related risk factors.Methods:Between June 2004 and December 2021, retrospective review was conducted for the relevant clinical data and age distribution of 1044 HT recipients aged ≥18 year at Fuwai Hospital. The study population was assigned into two groups of elder (≥60 year, n=877) and non-elder (<60 year, n=157). Subgroup analysis was made between recipients aged <65 year (n=107) and those aged ≥ 65 year (n=50) in elder group. Baseline demographic profiles, clinical data, in-hospital and one-year post-transplant mortality and long-term survival were compared between two groups. Then a further comparison of long-term survival was conducted among the groups of non-elder, elder aged <65 year and elder aged ≥65 year. Cox proportional risk regression and multivariate Logistic regression models were utilized for examining the relevant risk factors for cumulative survival rate and short-term mortality. Kaplan-Meier analysis was employed for plotting survival curves and Log-rank test for comparison. Multivariate Cox proportional risk regression model was utilized for examining the relevant risk factors for cumulative survival rate and multivariate Logistic regression model for analyzing the relevant risk factors for short-term mortality. After adjusting for other confounding factors, the impact of recipient age on survival post-HT was determined.Results:The number of elderly HT recipients spiked annually at our center while average age of adult recipients and average age of elderly recipients have remained relatively constant. The median follow-up period was 6.5 years. Regarding baseline data, statistically significant differences existed in ratio of males [84.7%(113/157) vs 77.5%(687/877)], hypertension history [20.4%(32/157) vs 8.9%(79/877)], smoking history [47.1%(74/157) vs 36.1%(320/877)], diabetic history [33.8%(53/157) vs 14.7%(130/877)], preoperative ICD/CRT/CRT-D implantation [28.0%(44/157) vs 18.0%(160/877)], value of creatinine [(105.3±25.3) vs (96.8±35.0) μmol/L], IMPACT score [(6.9±2.4) vs (4.2±2.9) point], serum total bilirubin [19.7(13.6, 30.3) vs 23.7(15.8, 36.8) μmol/L], mean pulmonary arterial pressure [(26.0±10.3) vs (29.7±11.0) mmHg (1 mmHg=0.133 kPa)] and ischemic duration [(274.7±105.6) vs (296.0±120.4) min] (all P<0.05). No significant inter-group difference existed in in-hospital mortality [4.5%(7/157) vs 4.7%(42/887)] or 1-year mortality [5.7%(9/157) vs 6.5%(58/887)] ( P=0.88, P=0.70); in-hospital mortality and 1-year postoperative mortality of recipients aged ≥65 years 10.0%(5/50) and 14.0%(7/50) were both higher than those aged <65 year [1.9%(2/107), 1.9%(2/107)]. The differences were both statistically significant ( P=0.02, P<0.01). Kaplan-Meier survival analysis indicated that long-term survival rate was lower in elder group than that in non-elder group and the difference was statistically significant ( P=0.046). Long-term survival rate of elders aged ≥65 year was lower than that of non-elders aged <65 year and the difference was statistically significant ( P<0.01). Regression analysis indicated that age of recipient ≥65 year, preoperative creatinine ≥133 μmol/L, preoperative total bilirubin ≥25.65 μmol/L and preoperative support of extracorporeal membrane oxygenation (ECMO) were independent risk factors for short/long-term mortality post-HT. Conclusion:Although long-term prognosis of elderly recipients is slightly worse than that of non-elderly ones, in-hospital mortality and one-year postoperative mortality are similar between two groups. For elderly recipients with fewer comorbidities and better preoperative status, they should not be excluded from HT based solely upon age. The long-term prognosis of recipients aged ≥65 year remains poor and HT decisions should be made carefully.
6.Application of prone position in severe ARDS caused by pneumocystis jirovecii pneumonia after kidney transplantation
Li TIAN ; Xiaonan FANG ; Ling ZHANG ; Ke LI
Organ Transplantation 2023;14(6):847-854
Objective To investigate the improvement of oxygenation after the treatment of prone position in patients with severe acute respiratory distress syndrome (ARDS) caused by pneumocystis jirovecii pneumonia (PJP) after kidney transplantation. Methods Clinical data of 5 cases of moderate and severe ARDS caused by PJP after kidney transplantation were analyzed retrospectively, and clinical characteristics, treatment regimen and prognosis were summarized. Results Clinical manifestations of 5 patients were fever, dry cough, chest tightness, shortness ofbreath,sweating and fatigue, and body temperature fluctuated between 38 ℃ and 39 ℃, percutaneous arterial oxygen saturation(SpO2) was gradually decreased, and respiratory distress symptoms were worsened. Pulmonary CT scan showed diffuse ground-glass shadow. After transfer to intensive care unit (ICU), immunosuppressive drugs were terminated, and all patients were given with compound sulfamethoxazole, caspofungin, low-dose glucocorticoids against pneumocystis jirovecii (PJ), oxygen therapy and other symptomatic supportive treatments. Four patients diagnosed with severe ARDS upon admission to ICU were treated in a prone position. One patient with moderate ARDS was not kept in a prone position. At 1 d after treatment in a prone position, partial pressure of arterial oxygen (PaO2) and oxygenation index were increased, whereas alveolar-arterial oxygen difference (A-aDO2) was decreased compared with before treatment (allP<0.05). Compared with 1 d after treatment, SpO2, PaO2 and oxygenation index were all increased, while A-aDO2 was decreased at 4 d after treatment (all P<0.05). Box diagram showed that oxygenation index showed an overall upward trend after prone-position treatment, whereas A-aDO2 showed an overall downward trend. The length of ICU stay of 5 patients was 14 (8, 29) d. All patients in a prone position did not develop complications, such as skin pressure sore, tube detachment and tube displacement, etc. Among 5 patients, 4 patients were mitigated, and 1 patient died of septic shock and multiple organ failure. Conclusions For both conscious and intubated patients, a prone position may significantly improve oxygenation and prognosis of patients with severe ARDS caused by PJP after kidney transplantation. Early diagnosis and accurate and standardized treatment play a pivotal role in enhancing cure rate.
7.Mechanism of interleukin-22 regulating insulin resistance in polycystic ovary syndrome rats
Xiaochen MA ; Yujuan QI ; Ying LIU ; Fang SUN ; Xiaonan YAN ; Bei ZHANG
Chinese Journal of Reproduction and Contraception 2023;43(2):184-190
Objective:To evaluate the mechanism of pancreatic interleukin-22 (IL-22) signaling pathway regulating insulin resistance (IR) in polycystic ovary syndrome (PCOS) rats.Methods:Postnatal 21 d SD rats were divided into control group and PCOS group with 10 rats in each group based on numbers randomly generated by computer. PCOS rats implanted with a silastic tube filled with dihydrotestosterone (DHT) at dosage of 7.5 mg. Their body weight was monitored weekly. At the end of the experiment, the intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin test (IPITT) were conducted, the serum IL-22 and fasting insulin (FINS) were monitored through the enzyme-linked immunosorbent assay (ELISA), and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The location and differential expression of the interleukin-22 receptor 1 (IL-22R1) in pancreatic β cells were observed by immunofluorescence staining, and the expressions of the IL-22, Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3) proteins were detected by Western blotting.Results:Compared with control group, the body weight was increased [(420.50±10.26) g vs. (314.40±6.54) g, P=0.003] and the serum level of IL-22 in PCOS group was decreased [(9.86±1.41) ng/L vs. (16.07±4.68) ng/L, P=0.038]. The levels of FINS and HOMA-IR were higher in PCOS group than in control group [(17.97±2.86) mU/L vs. (13.05±2.12) mU/L, P=0.001; 4.46±0.80 vs. 2.99±0.61, P=0.001]. The glucose levels in IPGTT test were significantly elevated in PCOS group in 30 min, 60 min and 90 min compared with control group [(15.58±1.86) mmol/L vs. (12.54±1.60) mmol/L, P=0.010;(10.71±2.07) mmol/L vs. (8.33±1.02) mmol/L, P=0.026; (7.47±1.36) mmol/L vs. (6.28±0.72) mmol/L, P=0.013], as well as the area under curve (AUC) [(1 248.71±164.23) mmol/(L·min) vs. (1 007.29±102.29) mmol/(L·min), P=0.010]. Following IPITT, compared with control group, PCOS group showed significantly higher 60 min [(3.12±0.28) mmol/L vs. (2.60±0.28) mmol/L, P=0.031], 90 min [(2.62±0.17) mmol/L vs. (2.10±0.33) mmol/L, P=0.026] and 120 min glucose level [(2.28±0.25) mmol/L vs. (1.90±0.24) mmol/L, P=0.033], as well as the AUC [(414.60±23.06) mmol/(L·min) vs. (359.40±39.95) mmol/(L·min), P=0.044]. The immunofluorescence results suggested that IL-22R1 and INS were colocalized in pancreatic β cells and the expression of IL-22R1 was lower in PCOS group than in control group (48.26±3.83 vs. 63.44±2.66, P=0.031). Further, the levels of pancreatic IL-22 and p-STAT3 protein were significantly lower in PCOS group than in control group (0.82±0.09 vs. 1.01±0.06, P=0.025; 0.77±0.09 vs. 1.01±0.07, P=0.015). Conclusion:Our results demonstrated that the abnormality of IL-22 may result in IR through attenuating the activation of STAT3 signaling pathway and decreasing the level of p-STAT3 in the pancreatic tissue of PCOS rats.
8.Mechanism of interleukin-22 regulating insulin resistance in polycystic ovary syndrome rats
Xiaochen MA ; Yujuan QI ; Ying LIU ; Fang SUN ; Xiaonan YAN ; Bei ZHANG
Chinese Journal of Reproduction and Contraception 2023;43(2):184-190
Objective:To evaluate the mechanism of pancreatic interleukin-22 (IL-22) signaling pathway regulating insulin resistance (IR) in polycystic ovary syndrome (PCOS) rats.Methods:Postnatal 21 d SD rats were divided into control group and PCOS group with 10 rats in each group based on numbers randomly generated by computer. PCOS rats implanted with a silastic tube filled with dihydrotestosterone (DHT) at dosage of 7.5 mg. Their body weight was monitored weekly. At the end of the experiment, the intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin test (IPITT) were conducted, the serum IL-22 and fasting insulin (FINS) were monitored through the enzyme-linked immunosorbent assay (ELISA), and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The location and differential expression of the interleukin-22 receptor 1 (IL-22R1) in pancreatic β cells were observed by immunofluorescence staining, and the expressions of the IL-22, Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3) proteins were detected by Western blotting.Results:Compared with control group, the body weight was increased [(420.50±10.26) g vs. (314.40±6.54) g, P=0.003] and the serum level of IL-22 in PCOS group was decreased [(9.86±1.41) ng/L vs. (16.07±4.68) ng/L, P=0.038]. The levels of FINS and HOMA-IR were higher in PCOS group than in control group [(17.97±2.86) mU/L vs. (13.05±2.12) mU/L, P=0.001; 4.46±0.80 vs. 2.99±0.61, P=0.001]. The glucose levels in IPGTT test were significantly elevated in PCOS group in 30 min, 60 min and 90 min compared with control group [(15.58±1.86) mmol/L vs. (12.54±1.60) mmol/L, P=0.010;(10.71±2.07) mmol/L vs. (8.33±1.02) mmol/L, P=0.026; (7.47±1.36) mmol/L vs. (6.28±0.72) mmol/L, P=0.013], as well as the area under curve (AUC) [(1 248.71±164.23) mmol/(L·min) vs. (1 007.29±102.29) mmol/(L·min), P=0.010]. Following IPITT, compared with control group, PCOS group showed significantly higher 60 min [(3.12±0.28) mmol/L vs. (2.60±0.28) mmol/L, P=0.031], 90 min [(2.62±0.17) mmol/L vs. (2.10±0.33) mmol/L, P=0.026] and 120 min glucose level [(2.28±0.25) mmol/L vs. (1.90±0.24) mmol/L, P=0.033], as well as the AUC [(414.60±23.06) mmol/(L·min) vs. (359.40±39.95) mmol/(L·min), P=0.044]. The immunofluorescence results suggested that IL-22R1 and INS were colocalized in pancreatic β cells and the expression of IL-22R1 was lower in PCOS group than in control group (48.26±3.83 vs. 63.44±2.66, P=0.031). Further, the levels of pancreatic IL-22 and p-STAT3 protein were significantly lower in PCOS group than in control group (0.82±0.09 vs. 1.01±0.06, P=0.025; 0.77±0.09 vs. 1.01±0.07, P=0.015). Conclusion:Our results demonstrated that the abnormality of IL-22 may result in IR through attenuating the activation of STAT3 signaling pathway and decreasing the level of p-STAT3 in the pancreatic tissue of PCOS rats.
9.Cardiac allograft vasculopathy after heart transplantation: summary of a single-center long-term follow-up experience in Fuwai Hospital
Shanshan ZHENG ; Zhe ZHENG ; Yunhu SONG ; Jie HUANG ; Zhongkai LIAO ; Xiaonan FANG ; Sheng LIU
Organ Transplantation 2022;13(2):206-
Objective To summarize the incidence of cardiac allograft vasculopathy (CAV) after heart transplantation and the effect on the long-term survival of recipients. Methods Clinical data of 1 006 heart transplant recipients were retrospectively analyzed. Of 48 CAV patients, 4 cases were not included in this analysis due to lack of imaging evidence. A total of 1 002 recipients were divided into the CAV group (
10.Improvement effects of Dianxianqing granule on blood-brain barrier injury in Alzheimer ’s disease model mice
Yue QI ; Zhao LI ; Xia HOU ; Peichi HUANG ; Dong JIA ; Caiyu YANG ; Xiaobo DONG ; Xiaonan FANG ; Cairong MING
China Pharmacy 2022;33(9):1062-1067
OBJECTIVE To study the impr ovement effects of Dianxianqing granule on blood-brain barrier (BBB)injury in Alzheimer’s disease (AD)model mice by regulating NLR family pyrin domain containing 3(NLRP3)inflammasome signaling pathway. METHODS Totally 125 mice were randomly divided into sham operation group (n=25)and modeling group (n=100) by body weight. AD model was induced by intracerebroventricular injection of β-amyloid 25-35 in model group. Sham operation group was given normal saline with same method. The 100 model mice were randomly divided into model group ,Donepezil hydrochloride tablets group (positive control 1,1.3 mg/kg,i.g.),MCC950 group [positive control 2(selective NLRP 3 inhibitor),10 mg/kg,i.p.] and Dianxianqing granule group (12.48 g/kg by crude drug ,i.g.)by body weight ,with 25 mice in each group. Second day after modeling ,administration groups were given relevant medicine ,once a day ,for consecutive 21 d. Sham operation group and model group were given intragastric administration of water and intraperitoneal injection of normal saline. At last administration,the learning and memory ability was determined by Y maze test ,and blood-brain barrier permeability was measured by Evans blue leakage assay. The expressions of NLRP 3,anti-ionized calcium-binding adapter molecule 1(IBA-1),nuclear factor kappa B (NF-κB)p65,p53 upregulated modulator of apoptosis (PUMA),occludin(ocln),zonula occluden- 1(ZO-1)and claudin-5 (cldn5) in cerebral tissue were determined. RESULTS Compared with model group , spontaneous alternate response rate ,protein expressions of ocln ,cldn5 lnzyxyqy2003@163.com and ZO- 1 in cerebral tissue were increased significantly in administration groups (P<0.05 or P<0.01);Evans blue E-mail:jiadg2003@126.com content and protein expressions of NLRP 3,IBA-1,PUMA and NF-κB p65 in cerebral tissue were decreased significantly (P<0.05 or P<0.01). CONCLUSIONS Dianxianqing granule can improve BBB injury of AD model m ice by inhibiting NLRP 3 inflammasome signaling pathway.

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