1.Molecular Mechanism of Programmed Cell Death in Chronic Obstructive Pulmonary Disease and Traditional Chinese Medicine Intervention: A Review
Xin PENG ; Yunhui LI ; Lei LIANG ; Zheyu LUAN ; Hanxiao WANG ; Haotian XU ; Ziming DANG ; Jihong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):304-313
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that poses a significant threat to global health, exhibiting high morbidity, disability and mortality rate, with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex, and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death (PCD) is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine (TCM) is characterized by holistic regulation. In recent years, extensive research has been conducted in the TCM field focusing on modulating apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis for the treatment of COPD, yielding remarkable achievements. Therefore, this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD, aiming to provide insights and references for the clinical prevention, treatment and in-depth research of COPD.
2.Molecular Mechanism of Programmed Cell Death in Chronic Obstructive Pulmonary Disease and Traditional Chinese Medicine Intervention: A Review
Xin PENG ; Yunhui LI ; Lei LIANG ; Zheyu LUAN ; Hanxiao WANG ; Haotian XU ; Ziming DANG ; Jihong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):304-313
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that poses a significant threat to global health, exhibiting high morbidity, disability and mortality rate, with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex, and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death (PCD) is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine (TCM) is characterized by holistic regulation. In recent years, extensive research has been conducted in the TCM field focusing on modulating apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis for the treatment of COPD, yielding remarkable achievements. Therefore, this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD, aiming to provide insights and references for the clinical prevention, treatment and in-depth research of COPD.
3.The disease spectrum and laboratory characteristics of HIV and CMV co-infection
Yuan CHEN ; Yunhui LI ; Jing LIANG ; Li WANG ; Renlong ZHU ; Jiayue MA ; Yajie WANG
Chinese Journal of Laboratory Medicine 2025;48(4):498-504
Objective:To investigate the epidemiological characteristics, disease spectrum, and laboratory characteristics of human immunodeficiency virus/cytomegalovirus (HIV/CMV) co-infection, to provide references for clinical diagnosis and treatment.Methods:A cross-sectional study was conducted. Clinical information of 544 HIV/acquired immune deficiency syndrome (AIDS) patients who underwent CMV-DNA tests in Beijing Ditan Hospital in 2023 was collected. Participants were categorized into CMV-infection group (126 cases) and non-CMV-infection group (418 cases). The prevalence of CMV infection was analyzed. Univariate and multivariate logistic regression analysis were performed to identify risk factors for CMV/AIDS co-infection. The disease spectrum, laboratory characteristics, serum CMV-DNA load changes, treatment prognosis and outcomes in the CMV-infected group were evaluated. SPSS 27.0 was used for statistical analysis including the χ 2 test, Mann-Whitney U test, and Kruskal-Wallis H test. Results:The CMV infection rate among HIV/AIDS patients was 23.16% (126/544). Multivariate analysis identified low CD4 +T-lymphocyte count [<50 cells/μl; OR=27.962, 95% confidence interval( CI) 11.957-65.389] and high HIV RNA load (>1×10 5 copies/ml; OR=2.057, 95% CI 1.237-3.420) as independent risk factors for CMV co-infection in HIV/AIDS patients. Among the 126 HIV/CMV co-infected patients, CMV viremia was the most common manifestation (38.10%, 48/126), followed by CMV pneumonia (33.33%, 42/126) and CMV retinitis (11.90%, 15/126), which were mainly observed in patients with CD4 +T-lymphocyte counts <50 cells/μl. Of the patients receiving anti-CMV therapy, 80.70% (46/57) exhibited reduced CMV-DNA loads compared with baseline. Totally 29.82% (17/57) of those patients initiating antiretroviral therapy alone achieved CMV-DNA reduction compared with baseline. Overall, 80.16% (101/126) of patients achieved favorable prognosis. Conclusion:CMV co-infection is high in HIV/AIDS patients. Disease spectrum of HIV/CMV co-infection are dominated by CMV viremia and CMV pneumonia. Timely anti-CMV therapy is pivotal for reducing CMV-DNA loads and improving prognosis.
4.Effects of Dahuang Tangluo Pills on Intestinal Inflammatory Injury in Type 2 Diabetes Rats Based on TLR4/NF-κB Signaling Pathway
Zhongtang LIU ; Yonglin LIANG ; Xiangdong ZHU ; Dong AN ; Yankui GAO ; Min BAI ; Sichen ZHAO ; Yunhui ZHAO ; Xiaoli PEI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(2):91-98
Objective To explore the effects and mechanism of Dahuang Tangluo Pills on intestinal inflammatory injury in type 2 diabetes mellitus(T2DM)rats based on TLR4/NF-κB signaling pathway.Methods Eight ZDF(fa/+)rats were used as the blank group,and 40 ZDF(fa/fa)rats were fed with high-fat diet and then randomly divided into model group,metformin group(0.18 g/kg metformin)and TCM high-,medium-and low-dosage groups(2.16,1.08,0.54 g/kg Dahuang Tangluo Pills),respectively.The medication groups were gavaged with corresponding dosages for 12 consecutive weeks.The body mass and fasting blood glucose(FBG)of rats before and after intervention were detected.After the intervention,an oral glucose tolerance test(OGTT)was performed,the serum glucose(GLU),glycosylated serum protein(GSP),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)contents were detected.ELISA was used to detect serum fasting insulin(FINS),free fatty acids(FFA)and tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-22,lipopolysaccharide(LPS),secreted immunoglobulin A(SIgA)contents in colonic tissue.HE staining was used to observe the morphology of colonic tissue,and Western blot was used to detect the expressions of Toll like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,NF-κB inhibitor α(IκBα),p-IκBα,myeloid differentiation factor 88(MyD88)and zona pellucida protein-1(ZO-1)in colonic tissue.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.01),blood glucose significantly increased at all time points of OGTT(P<0.01),serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly increased,serum HDL-C and colonic tissue SIgA contents significantly decreased(P<0.01),with colonic tissue nuclear condensation,cytoplasmic dissolution,inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly increased,while the protein expressions of IκBα and ZO-1 significantly decreased(P<0.01).Compared with the model group,the body mass and FBG significantly decreased in metformin group,TCM high-and medium-dosage groups(P<0.01),blood glucose decreased at different time points of OGTT,and serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly decreased,serum HDL-C and colonic tissue SIgA contents significantly increased(P<0.05,P<0.01),with significant improvement in colonic tissue structure and reduction in inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly decreased,while the proteins expression of IκBα and ZO-1 significantly increased(P<0.05,P<0.01).Conclusion Dahuang Tangluo Pills may inhibit the activation of the TLR4/NF-κB signaling pathway,reduce the release of inflammatory factors,improve intestinal inflammatory injury,restore intestinal homeostasis,thereby improving glucose and lipid metabolism and exerting therapeutic effects on T2DM.
5.Effects of Dahuang Tangluo Pills on Intestinal Inflammatory Injury in Type 2 Diabetes Rats Based on TLR4/NF-κB Signaling Pathway
Zhongtang LIU ; Yonglin LIANG ; Xiangdong ZHU ; Dong AN ; Yankui GAO ; Min BAI ; Sichen ZHAO ; Yunhui ZHAO ; Xiaoli PEI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(2):91-98
Objective To explore the effects and mechanism of Dahuang Tangluo Pills on intestinal inflammatory injury in type 2 diabetes mellitus(T2DM)rats based on TLR4/NF-κB signaling pathway.Methods Eight ZDF(fa/+)rats were used as the blank group,and 40 ZDF(fa/fa)rats were fed with high-fat diet and then randomly divided into model group,metformin group(0.18 g/kg metformin)and TCM high-,medium-and low-dosage groups(2.16,1.08,0.54 g/kg Dahuang Tangluo Pills),respectively.The medication groups were gavaged with corresponding dosages for 12 consecutive weeks.The body mass and fasting blood glucose(FBG)of rats before and after intervention were detected.After the intervention,an oral glucose tolerance test(OGTT)was performed,the serum glucose(GLU),glycosylated serum protein(GSP),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)contents were detected.ELISA was used to detect serum fasting insulin(FINS),free fatty acids(FFA)and tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-22,lipopolysaccharide(LPS),secreted immunoglobulin A(SIgA)contents in colonic tissue.HE staining was used to observe the morphology of colonic tissue,and Western blot was used to detect the expressions of Toll like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65),p-NF-κB p65,NF-κB inhibitor α(IκBα),p-IκBα,myeloid differentiation factor 88(MyD88)and zona pellucida protein-1(ZO-1)in colonic tissue.Results Compared with the blank group,the body mass and FBG significantly increased in the model group(P<0.01),blood glucose significantly increased at all time points of OGTT(P<0.01),serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly increased,serum HDL-C and colonic tissue SIgA contents significantly decreased(P<0.01),with colonic tissue nuclear condensation,cytoplasmic dissolution,inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly increased,while the protein expressions of IκBα and ZO-1 significantly decreased(P<0.01).Compared with the model group,the body mass and FBG significantly decreased in metformin group,TCM high-and medium-dosage groups(P<0.01),blood glucose decreased at different time points of OGTT,and serum GLU,GSP,TG,TC,LDL-C,FINS,FFA and TNF-α,IL-6,IL-22,LPS contents in colonic tissue significantly decreased,serum HDL-C and colonic tissue SIgA contents significantly increased(P<0.05,P<0.01),with significant improvement in colonic tissue structure and reduction in inflammatory cell infiltration.The protein expressions of TLR4,NF-κB p65,p-NF-κB p65,p-IκBα and MyD88 in colonic tissue significantly decreased,while the proteins expression of IκBα and ZO-1 significantly increased(P<0.05,P<0.01).Conclusion Dahuang Tangluo Pills may inhibit the activation of the TLR4/NF-κB signaling pathway,reduce the release of inflammatory factors,improve intestinal inflammatory injury,restore intestinal homeostasis,thereby improving glucose and lipid metabolism and exerting therapeutic effects on T2DM.
6.The disease spectrum and laboratory characteristics of HIV and CMV co-infection
Yuan CHEN ; Yunhui LI ; Jing LIANG ; Li WANG ; Renlong ZHU ; Jiayue MA ; Yajie WANG
Chinese Journal of Laboratory Medicine 2025;48(4):498-504
Objective:To investigate the epidemiological characteristics, disease spectrum, and laboratory characteristics of human immunodeficiency virus/cytomegalovirus (HIV/CMV) co-infection, to provide references for clinical diagnosis and treatment.Methods:A cross-sectional study was conducted. Clinical information of 544 HIV/acquired immune deficiency syndrome (AIDS) patients who underwent CMV-DNA tests in Beijing Ditan Hospital in 2023 was collected. Participants were categorized into CMV-infection group (126 cases) and non-CMV-infection group (418 cases). The prevalence of CMV infection was analyzed. Univariate and multivariate logistic regression analysis were performed to identify risk factors for CMV/AIDS co-infection. The disease spectrum, laboratory characteristics, serum CMV-DNA load changes, treatment prognosis and outcomes in the CMV-infected group were evaluated. SPSS 27.0 was used for statistical analysis including the χ 2 test, Mann-Whitney U test, and Kruskal-Wallis H test. Results:The CMV infection rate among HIV/AIDS patients was 23.16% (126/544). Multivariate analysis identified low CD4 +T-lymphocyte count [<50 cells/μl; OR=27.962, 95% confidence interval( CI) 11.957-65.389] and high HIV RNA load (>1×10 5 copies/ml; OR=2.057, 95% CI 1.237-3.420) as independent risk factors for CMV co-infection in HIV/AIDS patients. Among the 126 HIV/CMV co-infected patients, CMV viremia was the most common manifestation (38.10%, 48/126), followed by CMV pneumonia (33.33%, 42/126) and CMV retinitis (11.90%, 15/126), which were mainly observed in patients with CD4 +T-lymphocyte counts <50 cells/μl. Of the patients receiving anti-CMV therapy, 80.70% (46/57) exhibited reduced CMV-DNA loads compared with baseline. Totally 29.82% (17/57) of those patients initiating antiretroviral therapy alone achieved CMV-DNA reduction compared with baseline. Overall, 80.16% (101/126) of patients achieved favorable prognosis. Conclusion:CMV co-infection is high in HIV/AIDS patients. Disease spectrum of HIV/CMV co-infection are dominated by CMV viremia and CMV pneumonia. Timely anti-CMV therapy is pivotal for reducing CMV-DNA loads and improving prognosis.
7.The prognostic value of serum Dnase1L3, CAR combined with MHR in decompensated hepatitis B cirrhosis patients
Yunhui WU ; Jingchao DONG ; Liang MIAO ; Jidong ZHANG
Journal of Chinese Physician 2024;26(1):76-81
Objective:To explore the prognostic value of serum deoxyribonuclease 1 like 3 (Dnase1L3), C-reactive protein/albumin ratio (CAR) combined with monocyte to high-density lipoprotein cholesterol ratio (MHR) in decompensated hepatitis B cirrhosis patients.Methods:A prospective selection was conducted on 236 decompensated hepatitis B cirrhosis patients (liver disease group) admitted to the Third Hospital of Qinhuangdao from January 2020 to December 2021, and 185 healthy volunteers (control group) who underwent outpatient physical examinations. The serum levels of Dnase1L3, CAR, MHR, and liver function were detected, and Pearson analysis was conducted to investigate the correlation between Dnase1L3, CAR, MHR, and liver function. Tracking the survival status of patients after 30 days of hospitalization, the risk factors affecting 30 day mortality in decompensated hepatitis B cirrhosis patients were analyzed using a multivariate logistic regression equation. The receiver operating characteristic (ROC) curve analysis was used to assess the value of Dnase1L3, CAR, and MHR in predicting 30 day in-hospital mortality in decompensated hepatitis B cirrhosis patients.Results:The serum levels of Dnase1L3, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBiL), CAR, and MHR in the liver disease group were higher than those in the control group (all P<0.05). The serum levels of Dnase1L3, CAR, and MHR in the liver disease group were positively correlated with AST, ALT, and TBiL (all P<0.05). Among 236 patients, 32 died within 30 days. Model for end-stage liver disease (MELD) scores>18, high Dnase1L3, high CAR, and high MHR were risk factors for 30 day mortality in decompensated hepatitis B cirrhosis patients (all P<0.05). The combined prediction of Dnase1L3, CAR, MHR, and MELD scores for 30 day mortality in decompensated patients with hepatitis B cirrhosis showed an area under the curve of 0.904, which was higher than the predicted values of 0.719, 0.678, 0.763, and 0.742 for individual indicators. Conclusions:The serum Dnase1L3 levels, CAR, and MHR are elevated in patients with decompensated hepatitis B cirrhosis, and are associated with the degree of liver function damage and mortality within 30 days of hospitalization. They have high value in predicting the prognosis of decompensated hepatitis B cirrhosis.
8.Activation of Nrf2/HO-1/NQO1 Signaling Pathway by Shenqi Tangluo Pill Improves Oxidative Stress Injury of Skeletal Muscle of Type 2 Diabetes Mellitus Mice
Xiaoli PEI ; Yonglin LIANG ; ⁎ ; Yongqiang DUAN ; ⁎ ; Xiangdong ZHU ; Bing SONG ; Min BAI ; Yunhui ZHAO ; Sichen ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):131-139
ObjectiveTo investigate the effect and mechanism of Shenqi Tangluo pill (SQTLP) on oxidative stress injury of skeletal muscle of type 2 diabetes mellitus (T2DM) mice based on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) pathway. MethodA total of 60 7-week-old male db/db mice [specific pathogen-free (SPF) grade] were selected and fed for one week for adaption. They were divided into the model control group, SQTLP low-, medium- and high-dose (19, 38, and 76 g·kg-1) groups and metformin group (0.26 g·kg-1) by gavage. Each group consisted of 12 mice. Twelve male db/m mice of the same age were selected as the blank group. The intervention was implemented continuously for 8 weeks. Fasting blood glucose (FBG) was detected. Fasting serum insulin (FINS) levels were detected by enzyme-linked immunosorbent assay (ELISA), and the homeostasis model assessment-insulin resistance (HOMA-IR) index and the homeostasis model assessment-insulin sensitivity index (HOMA-ISI) were calculated. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the contents of malondialdehyde (MDA) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) in skeletal muscle tissues were detected by biochemical kits. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in skeletal muscle tissues. The levels of reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE) in skeletal muscle tissue were detected by immunofluorescence (IF). The expression levels of Nrf2, HO-1, NQO1 and glutamate-cysteine ligase catalytic subunit (GCLC) proteins in skeletal muscle tissues were detected by Western blot. ResultCompared with those in the blank group, FBG, FINS and HOMA-IR in the model group were significantly increased (P<0.05), while HOMA-ISI was decreased (P<0.05). The results of OGTT and ITT showed that blood glucose was significantly increased at all time points (P<0.05), and glucose tolerance and insulin tolerance were significantly impaired. SOD and GSH-Px activities in skeletal muscle tissues were significantly decreased (P<0.05), and MDA and NADPH contents were significantly increased (P<0.05). In skeletal muscle tissues, the arrangement of muscle fibers was loose, the nucleus was disordered, and inflammatory cells were infiltrated. The expression levels of ROS and 4-HNE in skeletal muscle tissues were significantly increased (P<0.05). The protein expression levels of Nrf2, HO-1, NQO1 and GCLC in skeletal muscle tissues were significantly decreased (P<0.05). Compared with those in the model group, FBG, FINS and HOMA-IR in the metformin group were significantly decreased (P<0.05), while HOMA-ISI was increased (P<0.05). The results of OGTT and ITT showed that blood glucose in the metformin group was significantly decreased at all time points (P<0.05). The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased (P<0.05), while the contents of MDA and NADPH were significantly decreased (P<0.05). No obvious abnormality was found in the skeletal muscle tissue of the metformin group. The expressions of ROS and 4-HNE in skeletal muscle tissues were decreased (P<0.05). The protein expression levels of Nrf2, HO-1, NQO1 and GCLC in skeletal muscle tissues were significantly increased (P<0.05). Compared with those in the model group, FBG, FINS and HOMA-IR in the SQTLP medium- and high-dose groups were significantly decreased (P<0.05), while HOMA-ISI was increased (P<0.05). The results of OGTT and ITT showed that the glucose tolerance and insulin tolerance of mice were improved in each dose group of SQTLP. The GSH-Px activity in the SQTLP low-dose group was significantly increased (P<0.05), and the NADPH content was decreased (P<0.05). The activities of SOD and GSH-Px in the SQTLP medium- and high-dose groups were significantly increased (P<0.05), while the contents of MDA and NADPH were significantly decreased (P<0.05). The skeletal muscle tissue injury of mice in each dose group of SQTLP was ameliorated to different degrees. In the SQTLP medium- and high-dose groups, the expressions of ROS and 4-HNE were decreased (P<0.05), and the protein expression levels of Nrf2, HO-1, NQO1 and GCLC were significantly increased (P<0.05). Compared with those in the SQTLP low-dose group, FBG and HOMA-IR in the SQTLP high-dose group were significantly decreased (P<0.05), while HOMA-ISI was increased (P<0.05). The results of OGTT and ITT showed that the SQTLP high-dose group significantly improved the glucose tolerance and insulin tolerance of mice. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased (P<0.05), while the contents of MDA and NADPH were significantly decreased (P<0.05). No obvious abnormality was found in the skeletal muscle tissue, the expressions of ROS and 4-HNE were decreased (P<0.05), and the protein expression levels of Nrf2, HO-1, NQO1 and GCLC were significantly increased (P<0.05) in the skeletal muscle tissue of the SQTLP high-dose group. ConclusionSQTLP can significantly improve IR in T2DM mice, and the mechanism is related to SQTLP activating the Nrf2/HO-1/NQO1 signaling pathway, promoting the expression of antioxidant enzymes, and thus improving the oxidative stress injury in the skeletal muscle.
9.Progress in the Regulation of Aquaporin-2 by Traditional Chinese Medicine for the Prevention and Treatment of Diabetic Nephropathy
Pu ZHANG ; Shangzu ZHANG ; Xiangdong ZHU ; Lihong TANG ; Yongqiang DUAN ; Min BAI ; Yunhui ZHAO ; Jianqing LIANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(11):2921-2927
Diabetic kidney disease(DKD)is one of the major complications of diabetes mellitus(DM),which significantly affects the survival and quality of life of DM patients.Currently,existing first-line treatment approaches for DKD are ineffective in effectively preventing the occurrence and progression of DKD.Traditional Chinese medicine(TCM)has the advantages of"ultiple pathways,multiple targets,and multiple mechanisms"in treating DKD,and has a broad prospect in the treatment of DKD.Aquaporin-2(AQP2)is a membrane channel protein widely expressed in the kidneys,and its physiological function is highly similar to the function of kidney filtration and reabsorption.Studies have found that various effective components and related formulae of Chinese medicine can improve symptoms in DKD patients by inhibiting the abnormal expression of AQP2.This article provides a review on the role of AQP2 in DKD and the research progress of TCM intervention,aiming to provide insights and references for the development of drugs related to the prevention and treatment of DKD.
10.Mechanism of Dahuang Tangluo Pills in Improving Renal Inflammatory Injury in Diabetic Kidkdey Disease by Regulating AGEs/RAGE/IKK/NF-κB Pathway
Pu ZHANG ; Jianqing LIANG ; Xia YANG ; Min BAI ; Xiangdong ZHU ; Chunxia XUE ; Beibei SU ; Yunhui ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):77-85
ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease (DKD) in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose (FBG). Mice with FBG ≥ 16.7 mmol·L-1, increased urine output, and persistent albuminuria were considered successful in model establishment. After successful modeling, they were randomly divided into a model group, a dapagliflozin group (1.5 mg·kg-1·d-1), and high, medium, and low dose groups of Dahuang Tangluo pills (3.6, 1.8, 0.9 g·kg-1·d-1, respectively), with eight mice in each group. All medication groups were administered orally, while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks, the survival status of the mice was observed, and their body weight, FBG, and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining, Masson staining, and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products (AGEs) and receptors for advanced glycation end products (RAGE) proteins. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were utilized to detect the gene and protein expression levels of AGEs, RAGE, inhibitor of nuclear factor-κB (NF-κB) kinase (IKK), and NF-κB in the renal tissues of mice in each group. ResultCompared with control group, the model group showed a significant increase in body weight, FBG, serum creatinine (SCr), urinary microalbumin/urine creatinine ratio (ACR), total cholesterol (TC), and triglycerides (TG) (P<0.05). The levels of intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in renal tissues were significantly elevated (P<0.05). Renal histopathological staining and electron microscopy revealed loose arrangement, gaps, structural disarray, mesangial proliferation, and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE, IKK, and NF-κB genes in renal tissues (P<0.05). Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues (P<0.05). Western blot results showed a significant increase in the expression of AGEs, RAGE, IKK, and NF-κB proteins in renal tissues (P<0.05). After drug intervention, compared with model group, the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight, FBG, SCr, and ACR (P<0.05), and a significant decrease in TC in mouse serum (P<0.05), while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum (P<0.05). All treatment groups showed a significant reduction in ICAM-1, IL-6, and TNF-α in renal tissues (P<0.05). Renal histopathological staining and electron microscopy showed improved kidney injury, decreased collagen fiber deposition, and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE, IKK, and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups (P<0.05). Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups (P<0.05). Western blot results showed a significant decrease in the expression of AGEs, RAGE, IKK, and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups (P<0.05). ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice, possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.

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