1.Regulation of NLRP3 Inflammasome by Traditional Chinese Medicine in Treatment of Atopic Dermatitis: A Review
Minmin HU ; Aimin LIU ; Mengying MA ; Changyu WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):315-321
Atopic dermatitis (AD) is an atopic disease with a complex etiology and pathogenesis resulting from the interaction of multiple factors. The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is an important component of innate immunity and is involved in the onset and progression of AD, encompassing multiple processes such as inflammation, pyroptosis, and autophagy. Traditional Chinese medicine (TCM) has shown significant clinical efficacy in the treatment of AD and also offers advantages including flexible compatibility, multi-target effects, and low drug resistance. A large number of studies have shown that single Chinese medicinal components and compound prescriptions can treat atopic diseases by modulating the NLRP3 inflammasome. This article elaborates on the activation of the NLRP3 inflammasome and its influence on the pathogenesis and progression of AD, and summarizes recent studies on the mechanisms by which active constituents, extracts, and compound formulations of Chinese medicine treat AD through regulation of the NLRP3 inflammasome and related signaling pathways, with the aim of providing a reference for the clinical treatment of AD and the development of TCM.
2.Research on integrating the red doctor spirit into the training system of military medical cadets under the “five arts” concept
Xiaojuan WU ; Yan WU ; Changyong MA ; Qiuju ZHANG
Chinese Medical Ethics 2026;39(2):263-267
The new synergistic education model integrating the “five arts” medical talent cultivation philosophy and the red doctor spirit could form a virtuous cycle of “spiritual guidance-technological breakthrough-spiritual reshaping” in the field of military medical education. Addressing the existing challenges in the process of military medical cadets’ training, such as mission awareness, humanistic care, battlefield rescue, and emergency response, this study proposed integrating the red doctor spirit, characterized by political steadfastness, healing the wounded and rescuing the dying, selfless devotion, relentless pursuit of excellence, and seeking truth and innovation, into the training system under the guidance of the “five arts” philosophy, including establishing a foundation through Daoist arts, forging the soul with benevolence, empowering through academia, tempering through technology, and nurturing the mind through artistry. A cultivation model was constructed featuring “moral education as the priority and cultivating through soul-forging; military spirit as the root and medical professionalism as the foundation and training for warfare; mastery in medicine for battlefield success and cultivating talent through rigorous scholarship.” Furthermore, through pathways including the optimization and implementation of the curriculum system, the enhancement and innovation of practical teaching, the development and training of the faculty team, and the improvement and innovation of the evaluation system, this model assisted in achieve the goal of cultivating compound talents with “the red medicine essence plus the five arts foundation.” These talents also built their foundation on the “five arts” philosophy, forge their spirit with the red doctor spirit, and was tempered with battlefield adaptability.
3.Comparison of clinical efficacy of evolocumab and probucol after PCI in patients with ultra-high-risk atherosclerotic cardiovascular disease
Yi YUAN ; Na LI ; Haiying SUN ; Jing SUN ; Yongqiang MA ; Yan WU ; Guohong YANG ; Junxiang LIU
China Pharmacy 2026;37(5):645-649
OBJECTIVE To compare the efficacy and safety of evolocumab and probucol in patients with ultra-high-risk atherosclerotic cardiovascular disease (ASCVD) following percutaneous coronary intervention (PCI). METHODS A retrospective analysis was conducted on 156 ultra-high-risk ASCVD patients who underwent PCI in our institution between January 1, 2023 and December 31, 2024. According to the lipid-lowering regimen, the patients were categorized into evolocumab group ( n =86) and probucol group ( n =70). Changes in lipid parameters [total cholesterol (TC), low-density lipoprot ein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, lipoprotein (a), and lipid goal achievement rate ] , inflammatory markers [interleukin-6 (IL-6) and C-reactive protein (CRP) ] , and cardiac function indices (left ventricular ejection fraction, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, and N-terminal pro-B-type natriuretic peptide) were compared between two groups at baseline and after 6 months of treatment. The incidence of adverse clinical events during treatment, including acute myocardial infarction, in-stent restenosis, acute heart failure, cerebral hemorrhage, and stroke, was also evaluated. RESULTS No statistically significant differences were observed between the two groups at baseline ( P >0.05). After 6 months of treatment, both groups demonstrated significant improvements in lipid profiles (except HDL-C) and inflammatory markers compared to those at baseline ( P <0.05). The evolocumab group exhibited greater reductions in TC, LDL-C, IL-6, and CRP, along with a higher lipid target achievement rate, compared with the probucol group ( P <0.05). There were no statistically significant differences in the cardiac function-related indicators before and after treatment between the two groups, nor in the incidence of adverse events during the treatment ( P >0.05). CONCLUSIONS For ultra-high-risk ASCVD patients after PCI, both of the above treatment options are associated with improvements in blood lipid and inflammatory response, with good safety during short-term follow-up. Evolocumab shows superior efficacy in TC, LDL-C and inflammatory markers reduction and lipid target achievement, compared to probucol.
4.Analysis of diagnosis and treatment of Epstein-Barr virus-negative diffuse large B-cell lymphoma (GCB type) after kidney transplantation
Yan LI ; Xiaoyan ZHANG ; Xiang REN ; Tong XU ; Guohui WANG ; Ruochen QI ; Dongjuan WU ; Kepu LIU ; Weijun QIN ; Shuaijun MA
Organ Transplantation 2026;17(2):257-265
Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.
5.Mechanism of Yangjing Zhongyutang in Regulating SIRT1/PGC-1α Signaling Pathway to Promote Mitochondrial Function and Alleviate Oxidative Stress Damage in Rats with Diminished Ovarian Reserve
Ping ZHANG ; Lijuan YANG ; Shenghui CHEN ; Wenliang YAO ; Yuliang ZHOU ; Ling MA ; Huiying WU ; Yanwen XU ; Ziyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):46-55
ObjectiveTo observe the effects of Yangjing Zhongyutang (YJZYT) on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) signaling pathway in cyclophosphamide (CTX)-induced rats with diminished ovarian reserve (DOR), and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group (n=7) and a model group (n=35). Rats in the model group received a single intraperitoneal injection of CTX (90 mg·kg-1) to establish the DOR model. After modeling, estrous cycles were monitored for 7 consecutive days, and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling, rats were divided into groups for intervention: estradiol valerate group (0.09 mg·kg-1), and YJZYT high-, medium-, and low-dose groups (19.98, 9.99, 5.00 g·kg-1). The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state, body weight, and ovarian wet weight of rats were observed and recorded, and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Hematoxylin-eosin (HE) staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species (ROS) expression levels. Colorimetric assays were employed to measure adenosine triphosphate (ATP) and malondialdehyde (MDA) content in ovarian tissues. Quantitative Real-time polymerase chain reaction (Real-time PCR) was used to detect mitochondrial DNA (mtDNA) copy number and the mRNA expression levels of key genes including SIRT1, PGC-1α, nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). Western blot was performed to detect the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM. ResultsCompared with the blank group, rats in the model group exhibited disrupted estrous cycles, obviously reduced body weight, and decreased ovarian index (P<0.05). Ovarian histopathology revealed cortical thinning, loose structure, and a significant reduction in both primordial and growing follicles (P<0.01). Serum FSH and LH levels were significantly elevated (P<0.01), while E2 and AMH levels were obviously reduced (P<0.05, P<0.01). ATP content and mtDNA copy number decreased in ovarian tissue (P<0.01), ROS expression increased, MDA levels rose, while SOD and GSH-Px activities obviously decreased (P<0.05, P<0.01), mRNA and protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM were obviously downregulated (P<0.05, P<0.01). After treatment, compared with the model group, body weight and ovarian index obviously recovered in rats administered various doses of YJZYT (P<0.05), serum E2 and AMH levels increased, while FSH and LH levels obviously decreased (P<0.05, P<0.01), ovarian tissue ATP content and mtDNA copy number were up-regulated, ROS and MDA levels decreased, and antioxidant enzymes SOD and GSH-Px activity obviously increased (P<0.05, P<0.01), Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group (P<0.05, P<0.01), HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups, with a obviously increase in the number of primordial and growing follicles (P<0.05, P<0.01). Granulosa cells were neatly arranged, indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway, promoting mitochondrial biogenesis, enhancing mitochondrial function, and alleviating oxidative stress damage.
6.Mechanisms of Anemarrhenae Rhizoma Water Extract in Ameliorating Neuroinflammation in Alzheimer's Disease Model Rats via SIRT1/HMGB1/NF-κB Signaling Pathway
Fei WU ; Yuexia LI ; Qi HUANG ; Tianshi LI ; Chuanshan JIN ; Kai MA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):230-240
ObjectiveTo investigate the therapeutic effects of the Anemarrhenae Rhizoma water extract (AR) on Alzheimer's disease (AD) model rats and to explore its potential underlying mechanisms. MethodsMale rats were intraperitoneally injected with D-galactose (100 mg·kg-1) for 42 days, and on day 14, 1 μL of β-amyloid (Aβ25-35, 2 g·L-1) solution was injected into the hippocampus. Rats were randomly divided into a model group, low-dose AR (0.6 g·kg-1), medium-dose AR (1.2 g·kg-1), high-dose AR (2.4 g·kg-1), and a positive control group (donepezil, 5 mg·kg-1). Healthy rats receiving only a hippocampal injection of 1 μL of sterile saline served as the sham-operated group. From day 21, rats in the treatment groups were administered the corresponding drugs by gavage once daily for 21 consecutive days, while the blank control and model groups received an equal volume of saline. Learning and memory abilities were assessed using the Morris water maze. Brain tissue damage was observed by hematoxylin and eosin (HE) staining, and neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) in brain tissues were measured by enzyme-linked immunosorbent assay (ELISA). BV2 microglial cells were co-cultured with Aβ25-35 (40 μmol·L-1) for 2 h, and cell viability was determined by the CCK-8 assay to screen the optimal concentration of AR-containing serum (S-AR). Cells were divided into blank control, Aβ25-35, S-AR, EX527 [silent information regulator 1 (SIRT1) inhibitor], and S-AR+EX527 groups. Immunofluorescence staining was used to detect the expression of CD16, CD206, and high-mobility group box 1 (HMGB1). Western blot analysis was performed to measure the protein expression of CD16, inducible nitric oxide synthase (iNOS), CD206, arginase (Arg), and proteins related to the SIRT1/HMGB1/nuclear factor-κB (NF-κB) signaling pathway. ResultsIn vivo experiments showed that, compared with the sham-operated group, the model group exhibited reduced platform crossings and time spent in the target quadrant (P<0.01), prolonged escape latency, increased hippocampal neuronal apoptosis (P<0.01), and obvious hippocampal damage. The expression levels of IL-6, TNF-α, IL-10, CD16, and iNOS in brain tissues were significantly elevated (P<0.01), while CD206 and Arg protein expression showed an increasing trend without statistical significance. Compared with the model group, all AR-treated groups significantly increased platform crossings and target quadrant time (P<0.05, P<0.01), alleviated hippocampal damage, reduced escape latency and neuronal apoptosis, downregulated the expression of TNF-α, IL-6, CD16, and iNOS (P<0.05, P<0.01), and upregulated the expression of IL-10, CD206 and Arg (P<0.05, P<0.01). In vitro experiments demonstrated that, compared with the blank control group, the Aβ25-35 group showed increased fluorescence intensity of CD206, CD16, and HMGB1, as well as elevated protein expression of iNOS and CD16 (P<0.01), while CD206 and Arg protein expression exhibited an increasing trend without statistical significance. After S-AR intervention, CD206 fluorescence intensity and the protein expression of Arg and CD206 were significantly increased (P<0.01), whereas the fluorescence intensity of CD16 and HMGB1 and the protein expression of iNOS and CD16 were significantly decreased (P<0.01). These effects were reversed by EX527 (P<0.05, P<0.01). Furthermore, compared with the blank control group, the Aβ25-35 group showed significantly increased cytoplasmic HMGB1 expression and p-p65/p65 ratio (P<0.01), along with significantly decreased SIRT1 and nuclear HMGB1 expression (P<0.01). In contrast, the S-AR group exhibited opposite trends compared with the Aβ25-35 group, and the regulatory effects of S-AR on these proteins were reversed by EX527 (P<0.01). ConclusionAR exerts neuroprotective effects in AD model rats by regulating microglial polarization and alleviating neuroinflammation, potentially through modulation of the SIRT1/HMGB1/NF-κB signaling pathway.
7.Colonization, drug resistance, and molecular epidemiological characteristics of methicillin-resistant Staphylococcus aureus among dairy farm workers in Xinjiang
Jiguo JIN ; Zhaojie WANG ; Yanggui CHEN ; Xixiao MA ; Wanting XU ; Xingyu WANG ; Xiangnan WEI ; Fan WU ; Xintao DANG ; Xueying XIANG ; Jianyong WU ; Fuye LI
Journal of Environmental and Occupational Medicine 2026;43(2):201-207
Background Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen for both human bloodstream infections and mastitis in cows. However, little attention has been paid to the cross-host transmission of MRSA from cows to high-risk groups in China. Objective To determine the MRSA colonization rates among dairy cows and dairy farm workers in Xinjiang, identify the antibiotic resistance profiles and molecular characteristics of the isolates, and provide scientific evidence for the formulation of targeted infection control strategies. Method A cross-sectional survey combined with laboratory pathogen analysis was conducted. From June to August 2024, large-scale dairy farms in Xinjiang region were selected as study sites. Nasal swabs (n=96) and skin swabs (n=39) were collected from workers, and bovine nasal swab samples (n=109) were collected simultaneously. All samples were subjected to MRSA isolation, cultivation, and identification, followed by antibiotic susceptibility testing to characterize resistance phenotypes. Staphylococcus aureus protein A (Spa) typing was performed to determine strain genotypes and elucidate MRSA colonization rates and molecular epidemiological patterns. Results A total of 35 MRSA strains was successfully isolated from 244 samples. The MRSA colonization rates among dairy farm workers and dairy cows were 20.83% (20/96) and 12.84% (14/109), respectively, with an overall isolation rate of 14.34% (35/244). Among the workers, the nasal colonization rate was 16.67% (16/96), and the skin colonization rate was 12.82% (5/39). One worker exhibited MRSA colonization at multiple body sites. All MRSA strains were resistant to cefoxitin (100%, 35/35). The resistance rates to erythromycin and clindamycin were 42.86% (15/35) and 34.29% (12/35), respectively. Thirteen strains showed a multidrug-resistant phenotype, whereas all strains were susceptible to vancomycin. The MRSA isolates exhibited high genetic diversity, with 13 Spa types identified, among which t441 was the most prevalent (8 strains). Both t441 and t034 types were detected in samples from both the dairy cows and their handlers. These two Spa types also carried and stably inherited specific resistance combinations, including erythromycin–clindamycin–cefoxitin and ciprofloxacin–erythromycin–clindamycin–gentamicin–cefoxitin–tetracycline, and a statistically significant association was also observed between the two resistance profiles and the bacterial types (P < 0.001). In addition, one novel Spa type strain was identified. Conclusion MRSA colonization rates among dairy cows and dairy farm workers in Xinjiang are relatively high, with evidence of multi-site colonization. The isolates exhibit high levels of multidrug resistance and genetic diversity, indicating a potential risk of cross-host transmission.
8.Forty Cases of Mid-Stage Diabetes Kidney Disease Patients of Blood Stasis Syndrome Treated with Huayu Tongluo Formula (化瘀通络方) as an Adjunct Therapy: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial
Yun MA ; Kaishuang WANG ; Shuang CAO ; Bingwu ZHAO ; Lu BAI ; Su WU ; Yuwei GAO ; Xinghua WANG ; Dong BIAN ; Zhiqiang CHEN
Journal of Traditional Chinese Medicine 2025;66(6):588-595
ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula (化瘀通络方, HTF) in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center, randomized, double-blind, placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment, the treatment group additionally taking HTF, while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein (24 h-UTP), serum albumin (Alb), glycated hemoglobin (HbA1c), and serum creatinine (Scr).The secondary outcomes included changes in levels of endothelin-1 (ET-1), nitric oxide (NO), vascular endothelial growth factor (VEGF), and traditional Chinese medicine (TCM) syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment, 24 h-UTP, ET-1, and VEGF levels significantly decreased (P<0.05), Alb and NO levels significantly increased (P<0.05); while the TCM syndrome scores for edema, lumbar pain, numbness of limbs, dark purple lips, dark purple tongue or purpura, and thin, rough pulse all significantly decreased (P<0.05). In the control group, no significant changes were observed in any of the indicators after treatment (P>0.05).Compared with the control group, the treatment group showed significant reductions in 24 h-UTP, ET-1, and VEGF levels, and increases in Alb and NO levels (P<0.05). The TCM syndrome scores for edema, lumbar pain, dark purple tongue or purpura, and thin, rough pulse were all lower in the treatment group than in the control group (P<0.05). The total effective rate of TCM syndrome in the treatment group was 59.09% (26/44), and the overall clinical effective rate was 45.45% (20/44). In the control group, these rates were 15.22% (7/46) and 8.7% (4/46), respectively, with the treatment group showing significantly better outcomes (P<0.05). A total of 7 adverse events occurred across both groups, with no significant difference (P>0.05). No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine, HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.
9.Effect and mechanism of BYL-719 on Mycobacterium tuberculosis-induced differentiation of abnormal osteoclasts
Jun ZHANG ; Jian GUO ; Qiyu JIA ; Lili TANG ; Xi WANG ; Abudusalamu·Alimujiang ; Tong WU ; Maihemuti·Yakufu ; Chuang MA
Chinese Journal of Tissue Engineering Research 2025;29(2):355-362
BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.
10.Wen-Shen-Tong-Du Decoction promoting spinal cord injury repair in mice
Ruihua ZHAO ; Sixian CHEN ; Yang GUO ; Lei SHI ; Chengjie WU ; Mao WU ; Guanglu YANG ; Haoheng ZHANG ; Yong MA
Chinese Journal of Tissue Engineering Research 2025;29(6):1118-1126
BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P<0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P<0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P<0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P<0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P<0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P<0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P<0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P<0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P<0.05),as well as a significant increase in Bax protein expression(P<0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P<0.05),as well as a significant decrease in Bax protein expression(P<0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.

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