1.Investigating Effect of Xianglian Huazhuo Prescription on Cell Cycle and Proliferation in Rats with Chronic Atrophic Gastritis Through TGF-β1/Smads Signaling Pathway
Yican WANG ; Jie WANG ; Yirui CHENG ; Xiaojing LI ; Yibin MA ; Qiuhua LIU ; Ziwei LIU ; Yuxi GUO ; Pengli DU ; Yanru CAI ; Yao DU ; Zheng ZHI ; Bolin LI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):128-136
ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription (XLHZ) in treating chronic atrophic gastritis (CAG) by regulating cell cycle and inhibiting proliferation, using bioinformatics technology and animal experiments. MethodsDifferential expressed genes (DEGs) related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis (WGCNA) was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction (PPI) analysis of genes was conducted using the Protein Interaction Platform (STRING) database to search the super hub gene (hub 2.0), and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group, and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine (MNNG) + sodium salicylate". The successfully modeled rats were randomly divided into the model group, XLHZ-H, XLHZ-M, and XLHZ-L groups (36, 18, 9 g·kg-1, respectively), and Morodan group (1.4 g·kg-1). Each group was given corresponding intervention for 60 days. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β1, Smad2 and Smad3 proteins, S/G2/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue, and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified, including TGF-β1, suggesting the involvement of the TGF-β1 signaling pathway in the CAG pathogenesis. Compared with the normal group, the expressions of TGF-β1, Smad2, geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased (P<0.05), and the expression of Smad3 protein was decreased (P<0.05). Compared with the model group, the expressions of TGF-β1 and geminin in the gastric mucosa were decreased in the drug groups (P<0.05). The XLHZ-M group, XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 (P<0.05). The protein expression of Smad3 was significantly increased in XLHZ-M, XLHZ-H, and Morodan groups (P<0.05). Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators, and positively correlated with other indicators (P<0.01). ConclusionXLHZ may inhibit TGF-β1/Smads signaling pathway, regulate cell cycle, and inhibit proliferation in the treatment of CAG.
2.Investigating Effect of Xianglian Huazhuo Prescription on Cell Cycle and Proliferation in Rats with Chronic Atrophic Gastritis Through TGF-β1/Smads Signaling Pathway
Yican WANG ; Jie WANG ; Yirui CHENG ; Xiaojing LI ; Yibin MA ; Qiuhua LIU ; Ziwei LIU ; Yuxi GUO ; Pengli DU ; Yanru CAI ; Yao DU ; Zheng ZHI ; Bolin LI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):128-136
ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription (XLHZ) in treating chronic atrophic gastritis (CAG) by regulating cell cycle and inhibiting proliferation, using bioinformatics technology and animal experiments. MethodsDifferential expressed genes (DEGs) related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis (WGCNA) was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction (PPI) analysis of genes was conducted using the Protein Interaction Platform (STRING) database to search the super hub gene (hub 2.0), and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group, and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine (MNNG) + sodium salicylate". The successfully modeled rats were randomly divided into the model group, XLHZ-H, XLHZ-M, and XLHZ-L groups (36, 18, 9 g·kg-1, respectively), and Morodan group (1.4 g·kg-1). Each group was given corresponding intervention for 60 days. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β1, Smad2 and Smad3 proteins, S/G2/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue, and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified, including TGF-β1, suggesting the involvement of the TGF-β1 signaling pathway in the CAG pathogenesis. Compared with the normal group, the expressions of TGF-β1, Smad2, geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased (P<0.05), and the expression of Smad3 protein was decreased (P<0.05). Compared with the model group, the expressions of TGF-β1 and geminin in the gastric mucosa were decreased in the drug groups (P<0.05). The XLHZ-M group, XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 (P<0.05). The protein expression of Smad3 was significantly increased in XLHZ-M, XLHZ-H, and Morodan groups (P<0.05). Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators, and positively correlated with other indicators (P<0.01). ConclusionXLHZ may inhibit TGF-β1/Smads signaling pathway, regulate cell cycle, and inhibit proliferation in the treatment of CAG.
3.Analysis of factors influencing visual prognosis after glucocorticoid pulse therapy in first-onset demyelinating optic neuritis
Bei HE ; Li MA ; Yang ZHANG ; Xiaomei WEI ; Yibin XI ; Xiaowei KANG
Chinese Journal of Ocular Fundus Diseases 2025;41(6):444-450
Objective:To observe and analyze the subtype-specific prognostic factors for visual recovery in patients with demyelinating optic neuritis (DON) after glucocorticoid pulse therapy.Methods:A retrospective cohort study. A total of 195 patients (249 eyes) with DON diagnosed by ophthalmology examination at Department of Ophthalmology, Xi'an People's Hospital (Xi'an Fourth Hospital) from January 2021 to December 2024 were included in the study. According to the results of serum antibody detection and clinical diagnostic criteria, the patients were divided into the neuromyelitis optica spectrum disorder (NMOSD)-associated optic neuritis (ON) (NMOSD-ON) group, the myelin oligodendrocyte glycoprotein antitide-associated ON (MOG-ON) group, and the double antibody negative ON group. They were 51 cases (58 eyes), 72 cases (103 eyes), and 72 cases (88 eyes) respectively. Baseline clinical data, imaging characteristics, and treatment protocols were collected. The primary endpoints were complete visual recovery [best-corrected visual acuity (BCVA) ≥ 1.0] and moderate recovery (BCVA ≥0.5) at 3 months post-onset. Multivariate logistic regression was used to identify independent prognostic factors for visual outcomes within each subtype.Results:At 3 months post-onset, complete recovery rates were 9 (15.5%, 9/58) in the NMOSD-ON group, 64 (62.1%, 64/103) in the MOG-ON group, and 31 (35.2%, 31/88) in the double-seronegative ON group. The results of multivariate regression analysis showed that age [odds ratio ( OR) =0.901, 95% confidence interval ( CI) 0.854-0.950, P<0.001] and peak visual acuity ( OR=0.311, 95% CI 0.147-0.660, P=0.002) and the involvement of optic nerve length ≥1/2 ( OR=3.849, 95% CI 1.083-13.682, P=0.037) were the influencing factors for the complete recovery of visual acuity in the affected eyes of the double antibody negative ON group. Age ( OR=0.958, 95% CI 0.933-0.983, P=0.001) was the only influencing factor for the complete recovery of visual acuity in the affected eyes of the MOG-ON group. Peak visual acuity ( OR=0.288, 95% CI 0.090-0.927, P=0.037) and optic nerve involvement length ≥1/2 ( OR=19.974, 95% CI 1.905-209.559, P=0.013) were the influencing factors for the complete recovery of visual acuity in the affected eyes of the NMOSD-ON group. Age ( OR=0.936, 95% CI 0.890-0.983, P=0.009), time from onset to intravenous infusion of methylprednisolone sodium succinate intervention ( OR=0.854, 95% CI 0.759-0.961, P=0.009), optic disc edema ( OR=4.405, 95% CI 1.108-17.512, P=0.035) and peak visual acuity ( OR=0.13, 95% CI 0.046-0.365, P<0.001) were the influencing factors for the moderate recovery of visual acuity in the affected eyes of the double antibody negative ON group. Peak visual acuity was the only influencing factor for the moderate recovery of visual acuity in the MOG-ON group ( OR=0.060, 95% CI 0.010-0.352, P=0.002) and the NMOSD-ON group ( OR=0.163, 95% CI 0.053-0.500, P=0.001). Conclusions:The prognostic factors for visual recovery in patients with DON after glucocorticoid pulse therapy are subtype-specific. Peak visual acuity is a common predictor for all subtypes. For NMOSD-ON and double antibody-negative ON, attention should be paid to the length of optic nerve lesions. MOG-ON is age-related. Early intravenous infusion of methylprednisolone sodium succinate for double antiantibody negative ON is more likely to achieve moderate vision recovery.
4.Discussion on Traditional Chinese Medicine etiology and pathogenesis of bone metabolic damage after space flight
Space Medicine & Medical Engineering 2025;36(5):493-496
Bone damage in space medicine mainly refers to a series of pathological changes in bone tissue during space flight because the specific space environment affects the physiological state of astronauts.At present,the research on bone damage in aerospace medicine mainly focuses on abnormal bone metabolism and osteoporosis.With the continuous development of space medicine,more and more attention is paid to such problems,and the development of traditional Chinese medicine is even more icing on the cake.Traditional Chinese medicine has its own unique theory to elaborate.This paper focuses on the pathogenesis of bone metabolic damage in space medicine from three aspects:yin and yang,qi and blood,and viscera,as well as the prevention of astronauts'bodies and the later rehabilitation treatment.
5.Neferine alleviates intervertebral disc degeneration through KEAP1/NRF2/GPX4 and NF-κB signaling pathways
Hongjin WAN ; Yibin HU ; Xin WANG ; Kai ZHANG ; An QIN ; Peixiang MA ; Hui MA ; Jie ZHAO
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(3):261-270
Objective·To investigate the therapeutic effects of neferine(Nef)on intervertebral disc degeneration(IDD)and the underlying regulatory pathways.Methods·The effects of Nef on the viability and proliferation of nucleus pulposus cells were assessed using the cell counting kit-8(CCK-8)assay.Molecular docking software was employed to analyze the potential binding sites of Nef within the Kelch domain of kelch-like ECH-associated protein 1(KEAP1).Tumor necrosis factor-α(TNF-α)was used to induce ferroptosis and inflammation in nucleus pulposus cells.Western blotting was performed to detect the expression levels of nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(NRF2/GPX4)pathway-and nuclear factor-KB(NF-κB)pathway-related proteins under TNF-α stimulation with or without Nef.The effect of Nef on the metabolism of extracellular matrix in nucleus pulposus cells was evaluated using high-density cell culture.A needle puncture-induced IDD rat model was established,and 5 μL of 1.5 μmol/L Nef was injected twice into the intervertebral disc at the Co3/4 level(IDD+Nef group),while an equivalent volume of PBS was injected into the Co2/3 disc(IDD group).After 4 weeks,the intervertebral space height was detected by X-ray,disc degeneration was detected by magnetic resonance imaging,and disc structure was evaluated by histological staining.Results·The CCK-8 assay revealed that Nef at concentrations of 1.5 μmol/L and below did not inhibit the viability and proliferation of nucleus pulposus cells.Molecular docking results suggested that Nef might activate NRF2 by directly binding to the KEAP1 Kelch domain,thereby reducing the interaction between KEAP1 and NRF2.Western blotting indicated that Nef significantly increased the expression of the key ferroptosis-inhibiting proteins NRF2 and GPX4,while decreasing the expression of the phospho-P65 protein in the NF-κB pathway(all P<0.05).The high-density culture of nucleus pulposus cells demonstrated that Nef mitigated the TNF-α-induced degradation of the extracellular matrix(P<0.05).Animal study results showed that compared to the IDD group,the IDD+Nef group exhibited a greater intervertebral disc space height,a lower Pfirrmann grade(both P<0.05),and a reduced degree of histological degeneration.Conclusion·Nef may inhibit TNF-α-induced ferroptosis in nucleus pulposus cells by activating the KEAP1/NRF2/GPX4 pathway and reduce TNF-α-induced inflammation and extracellular matrix degradation by suppressing the NF-κB pathway,thereby alleviating IDD in rats.
6.Neferine alleviates intervertebral disc degeneration through KEAP1/NRF2/GPX4 and NF-κB signaling pathways
Hongjin WAN ; Yibin HU ; Xin WANG ; Kai ZHANG ; An QIN ; Peixiang MA ; Hui MA ; Jie ZHAO
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(3):261-270
Objective·To investigate the therapeutic effects of neferine(Nef)on intervertebral disc degeneration(IDD)and the underlying regulatory pathways.Methods·The effects of Nef on the viability and proliferation of nucleus pulposus cells were assessed using the cell counting kit-8(CCK-8)assay.Molecular docking software was employed to analyze the potential binding sites of Nef within the Kelch domain of kelch-like ECH-associated protein 1(KEAP1).Tumor necrosis factor-α(TNF-α)was used to induce ferroptosis and inflammation in nucleus pulposus cells.Western blotting was performed to detect the expression levels of nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(NRF2/GPX4)pathway-and nuclear factor-KB(NF-κB)pathway-related proteins under TNF-α stimulation with or without Nef.The effect of Nef on the metabolism of extracellular matrix in nucleus pulposus cells was evaluated using high-density cell culture.A needle puncture-induced IDD rat model was established,and 5 μL of 1.5 μmol/L Nef was injected twice into the intervertebral disc at the Co3/4 level(IDD+Nef group),while an equivalent volume of PBS was injected into the Co2/3 disc(IDD group).After 4 weeks,the intervertebral space height was detected by X-ray,disc degeneration was detected by magnetic resonance imaging,and disc structure was evaluated by histological staining.Results·The CCK-8 assay revealed that Nef at concentrations of 1.5 μmol/L and below did not inhibit the viability and proliferation of nucleus pulposus cells.Molecular docking results suggested that Nef might activate NRF2 by directly binding to the KEAP1 Kelch domain,thereby reducing the interaction between KEAP1 and NRF2.Western blotting indicated that Nef significantly increased the expression of the key ferroptosis-inhibiting proteins NRF2 and GPX4,while decreasing the expression of the phospho-P65 protein in the NF-κB pathway(all P<0.05).The high-density culture of nucleus pulposus cells demonstrated that Nef mitigated the TNF-α-induced degradation of the extracellular matrix(P<0.05).Animal study results showed that compared to the IDD group,the IDD+Nef group exhibited a greater intervertebral disc space height,a lower Pfirrmann grade(both P<0.05),and a reduced degree of histological degeneration.Conclusion·Nef may inhibit TNF-α-induced ferroptosis in nucleus pulposus cells by activating the KEAP1/NRF2/GPX4 pathway and reduce TNF-α-induced inflammation and extracellular matrix degradation by suppressing the NF-κB pathway,thereby alleviating IDD in rats.
7.Analysis of factors influencing visual prognosis after glucocorticoid pulse therapy in first-onset demyelinating optic neuritis
Bei HE ; Li MA ; Yang ZHANG ; Xiaomei WEI ; Yibin XI ; Xiaowei KANG
Chinese Journal of Ocular Fundus Diseases 2025;41(6):444-450
Objective:To observe and analyze the subtype-specific prognostic factors for visual recovery in patients with demyelinating optic neuritis (DON) after glucocorticoid pulse therapy.Methods:A retrospective cohort study. A total of 195 patients (249 eyes) with DON diagnosed by ophthalmology examination at Department of Ophthalmology, Xi'an People's Hospital (Xi'an Fourth Hospital) from January 2021 to December 2024 were included in the study. According to the results of serum antibody detection and clinical diagnostic criteria, the patients were divided into the neuromyelitis optica spectrum disorder (NMOSD)-associated optic neuritis (ON) (NMOSD-ON) group, the myelin oligodendrocyte glycoprotein antitide-associated ON (MOG-ON) group, and the double antibody negative ON group. They were 51 cases (58 eyes), 72 cases (103 eyes), and 72 cases (88 eyes) respectively. Baseline clinical data, imaging characteristics, and treatment protocols were collected. The primary endpoints were complete visual recovery [best-corrected visual acuity (BCVA) ≥ 1.0] and moderate recovery (BCVA ≥0.5) at 3 months post-onset. Multivariate logistic regression was used to identify independent prognostic factors for visual outcomes within each subtype.Results:At 3 months post-onset, complete recovery rates were 9 (15.5%, 9/58) in the NMOSD-ON group, 64 (62.1%, 64/103) in the MOG-ON group, and 31 (35.2%, 31/88) in the double-seronegative ON group. The results of multivariate regression analysis showed that age [odds ratio ( OR) =0.901, 95% confidence interval ( CI) 0.854-0.950, P<0.001] and peak visual acuity ( OR=0.311, 95% CI 0.147-0.660, P=0.002) and the involvement of optic nerve length ≥1/2 ( OR=3.849, 95% CI 1.083-13.682, P=0.037) were the influencing factors for the complete recovery of visual acuity in the affected eyes of the double antibody negative ON group. Age ( OR=0.958, 95% CI 0.933-0.983, P=0.001) was the only influencing factor for the complete recovery of visual acuity in the affected eyes of the MOG-ON group. Peak visual acuity ( OR=0.288, 95% CI 0.090-0.927, P=0.037) and optic nerve involvement length ≥1/2 ( OR=19.974, 95% CI 1.905-209.559, P=0.013) were the influencing factors for the complete recovery of visual acuity in the affected eyes of the NMOSD-ON group. Age ( OR=0.936, 95% CI 0.890-0.983, P=0.009), time from onset to intravenous infusion of methylprednisolone sodium succinate intervention ( OR=0.854, 95% CI 0.759-0.961, P=0.009), optic disc edema ( OR=4.405, 95% CI 1.108-17.512, P=0.035) and peak visual acuity ( OR=0.13, 95% CI 0.046-0.365, P<0.001) were the influencing factors for the moderate recovery of visual acuity in the affected eyes of the double antibody negative ON group. Peak visual acuity was the only influencing factor for the moderate recovery of visual acuity in the MOG-ON group ( OR=0.060, 95% CI 0.010-0.352, P=0.002) and the NMOSD-ON group ( OR=0.163, 95% CI 0.053-0.500, P=0.001). Conclusions:The prognostic factors for visual recovery in patients with DON after glucocorticoid pulse therapy are subtype-specific. Peak visual acuity is a common predictor for all subtypes. For NMOSD-ON and double antibody-negative ON, attention should be paid to the length of optic nerve lesions. MOG-ON is age-related. Early intravenous infusion of methylprednisolone sodium succinate for double antiantibody negative ON is more likely to achieve moderate vision recovery.
8.Clinical effect of anterolateral thigh flow-through chimeric perforator free flap transplantation in the treatment of upper limb complex tissue defects with main artery injury
Fei LIU ; Weiqi YAN ; Qiang MA ; Yibin LIU ; Zhibin YANG
Chinese Journal of Burns 2024;40(2):172-179
Objective:To investigate the clinical effect of anterolateral thigh flow-through chimeric perforator free flap transplantation in the treatment of upper limb complex tissue defects with main artery injury.Methods:The study was a retrospective observational study. From May 2019 to January 2022, 11 patients with upper limb complex tissue defects combined with main artery injury who met the inclusion criteria were admitted to the Department of Hand, Foot and Ankle Surgery of General Hospital of Ningxia Medical University, including 7 males and 4 females, aged from 18 to 56 years. After debridement, the area of skin and soft tissue defects was from 20 cm×6 cm to 32 cm×10 cm, and the exposed area of dead cavity or deep tissue was from 7 cm×4 cm to 10 cm×7 cm. Three patients had radial artery defects with a length of 4 to 7 cm; two patients had ulnar artery defects with a length of 5 to 8 cm; 4 patients had defects in both ulnar and radial arteries with a length of 3 to 7 cm; and in two patients, the ulnar, radial and brachial arteries were all defective with a length of 4 to 8 cm. The anterolateral thigh flow-through chimeric perforator flap was designed and cut. The skin flap area was from 22 cm×7 cm to 32 cm×11 cm, the chimeric muscle flap area was from 7 cm×4 cm to 10 cm×7 cm, and the length of the flow-through vessel in the "T" shaped vessel pedicle was from 4 to 8 cm. When transplanting the skin flap, the proximal end of the vascular pedicle was anastomosed with the proximal end of the recipient site, and the distal end of the vascular pedicle was anastomosed with the more normal blood vessel at the distal end of the forearm; the invalid cavity was filled with the muscle flap. The donor site wounds of tissue flap were closed directly or treated with skin grafting. After operation, the blood supply and survival of the flap, the survival of the distal limb, and the survival of the skin graft at the flap donor site were observed. Computed tomography angiography (CTA) was performed to observe the patency of the proximal and distal anastomotic arteries from 2 to 4 weeks after surgery. During follow-up, the texture of the flap, the survival of the grafted skin and the healing of the donor area were observed.Results:One patient (complete forearm disconnection) developed distal limb blood disorder on 5 days after surgery. CTA examination suggested embolization of the distal anastomosis of the flow-through artery. more muscle and skin and soft tissue necrosis of the distal limb showed in emergency exploration. So, amputation was performed ultimately. No vascular crisis occurred in the skin flaps of the remaining 10 patients, and all skin flaps, distal limbs and the skin grafts in flap donor sites survived well. Two to 4 weeks after surgery, the proximal and distal ends of the anastomosed arteries were good in the patency. Follow-up for 11-37 months, the flap texture was good, and all donor site wounds healed well.Conclusions:The use of anterolateral thigh flow-through chimeric perforator flap to repair upper limb complex tissue defects accompanied by main artery injury can improve the success rate of limb salvage, which can be promoted in clinical practice.
9.A review of studies on visual behavior analysis aided diagnosis of autism spectrum disorders.
Journal of Biomedical Engineering 2023;40(4):812-819
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviors. With the rapid development of computer vision, visual behavior analysis aided diagnosis of ASD has got more and more attention. This paper reviews the research on visual behavior analysis aided diagnosis of ASD. First, the core symptoms and clinical diagnostic criteria of ASD are introduced briefly. Secondly, according to clinical diagnostic criteria, the interaction scenes are classified and introduced. Then, the existing relevant datasets are discussed. Finally, we analyze and compare the advantages and disadvantages of visual behavior analysis aided diagnosis methods for ASD in different interactive scenarios. The challenges in this research field are summarized and the prospects of related research are presented to promote the clinical application of visual behavior analysis in ASD diagnosis.
Humans
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Autism Spectrum Disorder/diagnosis*
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Vision, Ocular
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Behavior
10.Effects of ginkgo biloba extract on oxidative stress and the balance of excitation/inhibition of pyramidal neurons in the medial prefrontal cortex of depressive model mice
Chuanan ZHU ; Xianhua ZHANG ; Jindong CHEN ; Yuping XIA ; Zhiyuan HUANG ; Zengming MA ; Bin XIE ; Yanying XIE ; Yibin XIE ; Guiwen LI
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(3):210-217
Objective:To investigate the effect of ginkgo biloba extract (GBE) on oxidative stress in medial prefrontal cortex and excitatory/inhibitory balance of pyramidal neurons in chronic unpredictable mild stress (CUMS)-induced depressive model mice.Methods:Totally 48 SPF grade 7-week-old male C57BL/6J mice were divided into 4 groups according to random number table method: control+ saline group (CTRL+ Veh), control+ GBE group (CTRL+ GBE), model+ saline group (CUMS+ Veh), model+ GBE group (CUMS+ GBE), with 12 mice in each group.Mice in CUMS+ Veh group and CUMS+ GBE group were established by CUMS method, and mice in CTRL+ GBE group and CUMS+ GBE group were intraperitoneally injected with GBE (70 mg/kg) once a day, and mice in CTRL+ Veh group and CUMS+ Veh group were injected intraperitoneally with 0.9% sodium chloride solution.Then, the sucrose preference test, forced swimming test (FST) and tail suspension test (TST) were performed to evaluate the depressive-like behavior of mice, and open field test (OFT) was performed to evaluate the autonomous locomotion and exploration ability and anxiety-like behavior.The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in mPFC were determined by ELISA.Spontaneous excitatory postsynaptic currents (sEPSC) and spontaneous inhibitory postsynaptic currents (sIPSC) were detected by whole-cell recording.SPSS 23.0 was used for data analysis and two-factor analysis of variance(whether to get GBE, whether to mold, show as GBE×CUMS) was used for statistical analysis.Results:(1) Behavioral results: the the time spent in center and total distance of OFT and sugar preference rate of the four groups of mice were compared, and the interaction of GBE×CUMS was significant( F=24.90, 4.82, 3.91, all P<0.05). The results of simple effect analysis showed that the time spent in center ((47.15±3.58) s), the total distance((19.33±0.86) m) and the sugar preference rate((59.11±8.79)%) of the mice in CUMS+ Veh group were lower than those in the CTRL+ Veh group((61.55±2.49) s, (23.24±1.21) m, (84.02±7.45) %) (all P<0.01), and the above indexes in CUMS+ GBE group ((56.51±3.53) s, (20.75±1.31) m, (70.80±11.79)%) were higher than those in CUMS+ Veh group (all P<0.05). In the immobility time of FST and TST of mice in the 4 groups, the interaction of GBE×CUMS were significant( F=85.53, 83.39, both P<0.01). The immobility time of FST and TST in CUMS+ Veh group were higher than those in CTRL+ Veh group (both P<0.01 ), and the above indexes in CUMS+ GBE group were lower than CUMS+ Veh group(both P<0.05). (2)The results of ELISA showed that the interaction of GBE×CUMS of SOD level of mice in the 4 groups was not significant ( F=3.52, P=0.07), but the main effects of GBE factor and CUMS factor were both significant ( F=4.69, 46.93, both P<0.05). The interaction of GBE×CUMS of MDA level was significant( F=16.61, P<0.01). The level of SOD in the CUMS+ Veh group was lower than that in the CTRL+ Veh group ( P<0.01), and the level of SOD in the CUMS+ GBE group was higher than that in the CUMS+ Veh group ( P<0.05). The level of MDA in the CUMS+ Veh group was higher than that of the CTRL+ Veh group ( P<0.01), and the level of MDA in CUMS+ GBE group was lower than that of the CUMS+ Veh group ( P<0.01). (3) The results of whole-cell recording showed that the interaction of GBE×CUMS of frequency and quantification of sEPSC in the four groups were significant ( F=5.45, 6.94, both P<0.05). The sEPSC frequency and quantification in the CUMS+ Veh group were lower than those in the CTRL+ Veh group (both P<0.01), and the sEPSC frequency and quantification in CUMS+ GBE group were higher than those of CUMS+ Veh group (both P<0.05). The interaction of GBE×CUMS of frequency and quantification of sIPSC in the four groups were significant ( F=7.78, 8.96, both P<0.01). The sIPSC frequency and quantification of the CUMS+ Veh group were higher than those of CTRL+ Veh group (both P<0.01), and the above indexes of CUMS+ GBE group were lower than those of CUMS+ Veh group (both P<0.01). As for the sEPSC/sIPSC ratio, GBE×CUMS interaction was significant ( F=5.45, P=0.02). The sEPSC/sIPSC ratio of CUMS+ Veh group (0.09±0.01) was lower than that of CTRL+ Veh group (0.28±0.04) ( P<0.01), and the sEPSC/sIPSC ratio of CUMS+ GBE group (0.14±0.03) was higher than that of CUMS+ Veh group ( P<0.05). Conclusion:Ginkgo biloba extract can improve the depression-like behavior of mice induced by CUMS, reduce the oxidative stress of mPFC and improve the excitation/inhibition balance of pyramidal neurons in depressive model mice.

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