OBJECTIVE: To compare the effects of different chest compression rates (60-140 times/min) on hemodynamic parameters, return of spontaneous circulation (ROSC), resuscitation success, and survival in a porcine model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). METHODS: Forty healthy male domestic pigs were randomly divided into five groups based on chest compression rate: 60, 80, 100, 120, and 140 times/min (n = 8). All animals underwent standard anesthesia and tracheal intubation. A catheter was inserted via the left femoral artery into the thoracic aorta to monitor aortic pressure (AOP), and another via the right external jugular vein into the right atrium to monitor right atrial pressure (RAP). In each group, animals were implanted with a stimulating electrode via the right external jugular vein to the endocardium, and ventricular fibrillation (VF) was induced by delivering alternating current stimulation, resulting in CA. After a 1-minute, manual chest compressions were performed at the assigned rate with a compression depth of 5 cm. The first defibrillation was delivered after 2 minutes of CPR. No epinephrine or other pharmacologic agents were administered during the entire resuscitation process. From 1 minute before VF induction to 10 minutes after ROSC, dynamic monitoring of AOP, coronary perfusion pressure (CPP), and partial pressure of end-tidal carbon dioxide (P_ETCO₂). Cortical ultrastructure was examined 24 hours post-ROSC using transmission electron microscopy. RESULTS: With increasing compression rates, both the total number of defibrillations and cumulative defibrillation energy significantly decreased, reaching their lowest levels in the 120 times/min group. The number of defibrillations decreased from (4.88±0.83) times in the 60 times/min group to (2.25±0.71) times in the 120 compressions/min group, and energy from (975.00±166.90)J to (450.00±141.42)J. However, both parameters increased again in the 140 times/min group [(4.75±1.04)times, (950.00±207.02)J], the differences among the groups were statistically significant (both P < 0.01). As compression frequency increased, P_ETCO₂, pre-defibrillation AOP and CPP significantly improved, peaking in the 120 times/min group [compared with the 60 times/min group, P_ETCO₂ (mmHg, 1 mmHg≈0.133 kPa): 18.69±1.98 vs. 8.67±1.30, AOP (mmHg): 95.13±7.06 vs. 71.00±6.41, CPP (mmHg): 14.88±6.92 vs. 8.57±3.42]. However, in the 140 times/min group, these values declined significantly again [P_ETCO₂, AOP, and CPP were (10.59±1.40), (72.38±11.49), and (10.36±4.57) mmHg, respectively], the differences among the groups were statistically significant (all P < 0.01). The number of animals achieving ROSC, successful resuscitation, and 24-hour survival increased with higher compression rates, reaching a peak in the 120 times/min group (compared with the 60 times/min group, ROSC: 7 vs. 2, successful resuscitation: 7 vs. 2, 24-hour survival: 7 vs.1), then decreased again in the 140 times/min group (the animals that ROSC, successfully recovered and survived for 24 hours were 3, 3, and 2, respectively). Transmission electron microscopy revealed that in the 60, 80, and 140 times/min groups, nuclear membranes in cerebral tissue were irregular and incomplete, nucleoli were indistinct, and mitochondria were swollen with reduced cristae and abnormal morphology. In contrast, the 100 times/min and 120 times/min groups exhibited significantly attenuated ultrastructural damage. CONCLUSIONS Among the tested chest compression rates of 60-140 times/min, a chest compressions frequency of 120 times/min is the most favorable hemodynamic profile and outcomes during CPR in a porcine CA model. However, due to the wide spacing between groups, further investigation is needed to determine the optimal compression rate range more precisely.
Animals ; Cardiopulmonary Resuscitation/methods* ; Swine ; Male ; Heart Arrest/therapy* ; Heart Massage/methods* ; Hemodynamics

OBJECTIVE: To investigate whether auraptene (AUR) exerts a protective effect on acute diquat (DQ)-induced liver injury in mice and explore its underlying mechanisms. METHODS: Forty SPF-grade healthy male C57BL/6 mice were randomly divided into normal control group (Control group), DQ poisoning model group (DQ group), AUR treatment group (DQ+AUR group), and AUR control group (AUR group), with 10 mice in each group. The DQ poisoning model was established via a single intraperitoneal injection of 40 mg/kg DQ aqueous solution (0.5 mL); Control group and AUR group received an equal volume of pure water intraperitoneally. Four hours post-modeling, DQ+AUR group and AUR group were administered 0.5 mg/kg AUR aqueous solution (0.2 mL) by gavage once daily for 7 consecutive days, while Control group and DQ group received pure water. Blood and liver tissues were collected after anesthesia on day 7. Liver ultrastructure was observed by transmission electron microscopy. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured via enzyme-linked immunosorbent assay (ELISA). Hepatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected using WST-1, thiobarbituric acid (TBA), and enzymatic reaction methods, respectively. Protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues was analyzed by Western blotting. RESULTS: Transmission electron microscopy revealed that mitochondria in the Control group exhibited mild swelling, uneven distribution of matrix, and a small number of cristae fractures. In the AUR group, mitochondria showed mild swelling, with no obvious disruption of cristae structure. In the DQ group, mitochondria demonstrated marked swelling and increased volume, matrix dissolution, loss and fragmentation of cristae, and extensive vacuolization. In contrast, the DQ+AUR group showed significantly reduced mitochondrial swelling, volume increase, matrix dissolution, cristae loss and fragmentation, and vacuolization compared to the DQ group. Compared with the DQ group, the DQ+AUR group exhibited significantly lower serum AST levels (U/L: 173.45±23.60 vs. 255.33±41.51), ALT levels (U/L: 51.77±21.63 vs. 100.70±32.35), and hepatic MDA levels (μmol/g: 12.40±2.76 vs. 19.74±4.10), along with higher hepatic GSH levels (mmol/g: 37.65±14.95 vs. 20.58±8.52) and SOD levels (kU/g: 124.10±33.77 vs. 82.81±22.00), the differences were statistically significant (all P < 0.05). Western blotting showed upregulated Nrf2 expression (Nrf2/β-actin: 0.87±0.37 vs. 0.53±0.22) and HO-1 expression (HO-1/β-actin: 1.06±0.22 vs. 0.49±0.08), and downregulated Keap1 expression (Keap1/β-actin: 0.82±0.12 vs. 1.52±0.76) and activated caspase-9 expression (activated caspase-9/β-actin: 1.16±0.28 vs. 1.71±0.30) in the DQ+AUR group compared to the DQ group (all P < 0.05). CONCLUSION AUR attenuates DQ-induced acute liver injury in mice by activating the Keap1/Nrf2 signaling pathway.
Animals ; Male ; Mice ; Mice, Inbred C57BL ; Liver/pathology* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Diquat/poisoning* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Apoptosis ; Coumarins

Acute carbon monoxide poisoning (ACMP) is a common harmful gas poisoning. Underwent systematic treatment and a 2-3 week pseudo-healing period, some ACMP patients may still develop delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). DEACMP is the most severe complication that could happen to ACMP patients and comes with an exceeding high disability rate. Early identification and adequate intervention measures of DEACMP are particularly crucial for preventing its occurrence in clinical practice. At present, multiple studies have found that after ACMP occurred, a series of biomarkers showed predictive value for detecting the occurrence and development of DEACMP. This paper reviews these biomarkers and their predictive effects on DEACMP, aiming to provide theoretical guidance for the prevention and intervention of DEACMP.

Acute carbon monoxide poisoning (ACMP) is a common harmful gas poisoning. Underwent systematic treatment and a 2-3 week pseudo-healing period, some ACMP patients may still develop delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). DEACMP is the most severe complication that could happen to ACMP patients and comes with an exceeding high disability rate. Early identification and adequate intervention measures of DEACMP are particularly crucial for preventing its occurrence in clinical practice. At present, multiple studies have found that after ACMP occurred, a series of biomarkers showed predictive value for detecting the occurrence and development of DEACMP. This paper reviews these biomarkers and their predictive effects on DEACMP, aiming to provide theoretical guidance for the prevention and intervention of DEACMP.

OBJECTIVE: To investigate the protective effect and mechanism of tumor necrosis factor receptor-associated factor 6 (TRAF6) inhibitor C25-140 on acute kidney injury (AKI) induced by acute diquat (DQ) poisoning in mice. METHODS: A total of 80 SPF grade healthy male C57BL/6 mice were randomly divided into the normal control group, DQ model group, C25-140 intervention group, and C25-140 control group, with 20 mice in each group. The DQ poisoning mouse model was established by using one-time intraperitoneal injection of 1 mL of 40 mg/kg DQ solution. The normal control group and C25-140 control group were injected with an equal amount of pure water into the peritoneal cavity. After 4 hours of model establishment, the C25-140 intervention group and C25-140 control group were given intraperitoneal injection of C25-140 5 mg/kg. The normal control group and DQ model group were given equal amounts of pure water, once a day for 7 consecutive days. After 7 days, the mice were anesthetized, eye blood was collected, and renal tissue was collected after sacrifice. The pathological changes of renal tissue were observed under a light microscope and renal tissue structure and mitochondrial changes were observed under transmission electron microscopy. The levels of serum creatinine (SCr) and blood urea nitrogen (BUN) were measured. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of serum interleukins (IL-6, IL-1β) and tumor necrosis factor-α (TNF-α). Western blotting was used to detect the protein expression levels of TRAF6, myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) in renal tissue. Chemical method was used to determine the content of serum malondialdehyde (MDA) and superoxide dismutase (SOD). RESULTS: During the observation period, there were no abnormal behaviors in the normal control group mice. The DQ model group mice gradually showed symptoms such as mental fatigue, fluffy fur, reduced activity, and low food intake after being exposed to the toxin, and severe cases resulted in death. The above symptoms were alleviated in the C25-140 intervention group compared to the DQ model group. Under light microscopy, HE staining showed infiltration of inflammatory cells, glomerulosclerosis, proximal tubular dilation, and vacuolization in the DQ model group, while the inflammatory response was reduced in the C25-140 intervention group compared to the DQ model group. Under transmission electron microscopy, the DQ model group showed relatively high levels of mitochondrial damage, severe swelling, increased volume, matrix dissolution, ridge fracture and loss. The degree of mitochondrial damage in the C25-140 intervention group was reduced compared to the DQ model group. Compared with the normal control group, the levels of serum SCr, BUN, IL-6, IL-1β, TNF-α, and MDA in the DQ model group were significantly increased, while the serum SOD level was significantly decreased. Compared with the DQ model group, the levels of serum SCr, BUN, IL-6, IL-1β, TNF-α, and MDA in the C25-140 intervention group were significantly reduced [SCr (μmol/L): 59.07±13.11 vs. 83.61±20.13, BUN (mmol/L): 25.83±9.95 vs. 40.78±11.53, IL-6 (ng/L): 40.76±7.03 vs. 83.33±21.83, IL-1β (ng/L): 53.87±7.82 vs. 91.74±12.53, TNF-α (ng/L): 102.52±32.13 vs. 150.92±31.75, MDA (μmol/L): 3.57±1.06 vs. 5.75±1.83], and the serum SOD level was significantly increased (kU/g: 162.52±36.13 vs. 122.72±22.13), and the differences were statistically significant (all P < 0.01). Western blotting results showed that the protein expression levels of TRAF6, NF-κB, and MyD88 in the renal tissue of DQ model group mice were significantly higher than those in the normal control group. The expression levels of the above-mentioned proteins in the C25-140 intervention group of mice were significantly lower than those in the DQ model group (TRAF6/β-actin: 1.05±0.36 vs. 1.74±0.80, NF-κB/β-actin: 0.57±0.07 vs. 1.03±0.75, MyD88/β-actin: 0.58±0.07 vs. 1.03±0.33, all P < 0.05). CONCLUSIONS TRAF6 inhibitor C25-140 can alleviate AKI induced by DQ poisoning in mice by regulating the Toll-like receptor 4 (TLR4)/TRAF6/NF-κB signaling pathway and downregulating the levels of inflammatory cytokines IL-1β, IL-6, and TNF-α.
Animals ; Male ; Acute Kidney Injury/prevention & control* ; Mice ; Mice, Inbred C57BL ; Diquat ; TNF Receptor-Associated Factor 6/metabolism* ; Interleukin-6/blood* ; Kidney/pathology* ; NF-kappa B/metabolism* ; Peptide Fragments

Objective:To investigate the impact of Adiponectin receptor agonists(AdipoRon)on renal aging induced by D-galactose(D-gal)in male C57BL/6J mice and explore potential mechanisms.Methods:Male C57BL/6J mice were randomly divided into three groups: a control group, a D-gal model group, and an AdipoRon group, each consisting of ten mice.The control group received saline through gavage and subcutaneous injection, the D-gal group received saline through gavage and D-gal through subcutaneous injection, and the AdipoRon group received AdipoRon through gavage and D-gal through subcutaneous injection.The treatment duration was eight weeks, following which blood and renal tissues were collected for testing.Kidney pathological changes were observed using Haematoxylin-Eosin(HE)staining, Masson staining, and electron microscopy.Levels of serum creatinine(SCr), urea nitrogen(BUN), and cystatin-C(Cys-C)in mice were measured using an automatic biochemical analyzer.Protein expression levels of P53, P21, P16INK4a, Silent mating-type information regulation 2 homolog 1(SIRT1), Nuclear factor E2-related factor 2(NRF2), and Klotho in renal tissues were determined through Immunohistochemical staining and Western blot.Results:The glomeruli exhibited sparse and irregular structure, with sclerosis and dilated capsular space.Renal tubules showed atrophy, while foot processes appeared fused and widened.A significant presence of blue-stained collagen fibers was noted in the renal interstitium of the D-gal group compared to the control group.Pathological damage to the kidneys was notably reduced in the AdipoRon group compared to the D-gal group.Levels of SCr(23.13±2.21 μmol/L), BUN(19.58±1.63 μmol/L), and Cys-C(0.15±0.02 μmol/L)were higher in the D-gal group than in the control group.Conversely, SCr(16.97±1.16 μmol/L), BUN(16.25±1.25 μmol/L), and Cys-C(0.12±0.01 μmol/L)levels in the AdipoRon group were lower than those in the D-gal group( F=66.61, 40.37, 48.77, all P<0.001).The expression levels of aging proteins like P53(1.68±0.11), P21(2.40±0.45), and P16INK4a(1.89±0.16)in the mice kidney tissue of the D-gal group were elevated compared to the control group.In contrast, anti-aging proteins such as SIRT1(0.46±0.04), NRF2(0.65±0.05), and Klotho(0.42±0.03)were decreased in the D-gal group versus the control group.The expression levels of aging proteins like P53(1.27±0.06), P21(1.84±0.35), and P16INK4a(1.10±0.14)in the AdipoRon group were reduced.Conversely, the expression levels of anti-aging proteins such as SIRT1(0.78±0.05), NRF2(0.87±0.07), and Klotho(0.65±0.06)were increased compared to the D-gal group( F=152.38, 44.45, 147.54, 219.69, 42.25, 166.49, all P<0.001). Conclusions:AdipoRon was found to potentially slow down D-gal-induced renal senescence in mice through activation of the SIRT1 signaling pathway.

Objective:To analyze the optical coherence tomography (OCT) imaging characteristics in patients with Coats disease and their value in predicting macular fibrosis.Methods:A nested case-control study was performed.A total of 43 patients (43 eyes) diagnosed with Coats disease through color fundus photography, ocular B-scan ultrasonography, fundus fluorescein angiography, and spectral-domain OCT examination were enrolled from January 2008 to October 2021 at the Xijing Hospital.Among them, there were 40 males and 3 females, aged from 2 to 60 years old, with a median age of 13 years.Macular fibrosis was used as an indicator of poor prognosis, and patients were divided into two groups based on whether macular fibrosis occurred at the end of follow-up.The differences in OCT characteristics between two groups were compared and logistic regression analysis was used to identify the risk factors for macular fibrosis.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Xijing Hospital of Fourth Military Medical University (No.KY20202009-C-1).Results:The OCT clinical features of 43 cases of Coats disease included intraretinal hard exudates in 43 eyes (100%), subretinal fluid in 21 eyes (48.8%), macular cysts in 17 eyes (27.9%), subretinal exudates in 9 eyes (20.9%), anterior retinal hyperreflective dots in 7 eyes (16.3%), epiretinal membrane in 21 eyes (48.8%), and intraretinal fluid in 22 eyes (51.2%).In color fundus photos of 41 eyes, 38 eyes (93.0%) had hard exudates distributed in the posterior pole and 27 eyes (65.9%) had the mid-peripheral region.OCT examination showed that hard exudates were distributed in the inner nuclear layer in 35 eyes (81.4%) and the outer nuclear layer in 33 eyes (76.7%).Among 21 eyes with exudative retinal detachment detected by OCT, 9 eyes (42.9%) were detected by fundus photography and 18 eyes (85.7%) were detected by B-scan ultrasonography.The proportions of eyes with subretinal fluid and subretinal exudates were higher in the macular fibrosis group than in the non-macular fibrosis group, and the differences were statistically significant ( χ2=20.755, P<0.001; χ2=6.133, P=0.013).Logistic regression analysis showed that the presence of subretinal fluid was a risk factor for macular fibrosis (odds ratio=48.345, 95% confidence interval: 4.272-547.066, P=0.002). Conclusions:OCT examination can detect subretinal fluid, subretinal exudates, macular cysts, macular exudates, and hyperreflective spots in the retina of patients with Coats disease.Subretinal fluid is a risk factor for macular fibrosis.

Objective:To investigate the protective effect of quercetin (QR) on acute liver injury induced by diquat (DQ) poisoning in mice and its mechanism.Methods:Eighty healthy male C57BL/6 mice with SPF grade were randomly divided into control group, DQ model group, QR treatment group, and QR control group, with 20 mice in each group. The DQ poisoning model was established by a one-time intraperitoneal injection of DQ solution (40 mg/kg); the control and QR control groups received equivalent amounts of distilled water through intraperitoneal injection. Four hours after modeling, the QR treatment group and the QR control group received 0.5 mL QR solution (50 mg/kg) through gavage. Meanwhile, an equivalent amount of distilled water was given orally to the control group and the DQ model group. The treatments above were administered once daily for seven consecutive days. Afterwards, the mice were anesthetized, blood and liver tissues were collected for following tests: changes in the structure of mice liver tissue were observed using transmission electron microscopy; the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using enzyme linked immunosorbent assay (ELISA); the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured using the water-soluble tetrazolium-1 (WST-1) method, the thiobarbituric acid (TBA) method, and enzymatic methods, respectively; the protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues were detected using Western blotting.Results:Severe mitochondrial damage was observed in the liver tissues of mice in the DQ model group using transmission electron microscopy, yet mitochondrial damage in the QR treatment group showed significant alleviation. Compared to the control group, the DQ model group had significantly increased levels of MDA in liver tissue, serum AST, and ALT, yet had significantly decreased levels of GSH and SOD in liver tissue. In comparison to the DQ model group, the QR treatment group exhibited significant reductions in serum levels of ALT and AST, as well as MDA levels in liver tissue [ALT (U/L): 52.60±6.44 vs. 95.70±8.00, AST (U/L): 170.45±19.33 vs. 251.10±13.09, MDA (nmol/mg): 12.63±3.41 vs. 18.04±3.72], and notable increases in GSH and SOD levels in liver tissue [GSH (μmol/mg): 39.49±6.33 vs. 20.26±3.96, SOD (U/mg): 121.40±11.75 vs. 81.67±10.01], all the differences were statistically significant (all P < 0.01). Western blotting results indicated that the protein expressions of Nrf2 and HO-1 in liver tissues of the DQ model group were significantly decreased compared to the control group. On the other hand, the protein expressions of Keap1 and activated caspase-9 were conspicuously higher when compared to the control group. In comparison to the DQ model group, the QR treatment group showed a significant increase in the protein expressions of Nrf2 and HO-1 in liver tissues (Nrf2/β-actin: 1.17±0.08 vs. 0.92±0.45, HO-1/β-actin: 1.53±0.17 vs. 0.84±0.09). By contrast, there was a notable decrease in the protein expressions of Keap1 and activated caspase-9 (Keap1/β-actin: 0.48±0.06 vs. 1.22±0.09, activated caspase-9/β-actin: 1.17±0.12 vs. 1.59±0.30), the differences were statistically significant (all P < 0.01). Conclusion:QR may reduce acute liver injury induced by DQ poisoning in mice via activating Keap1/Nrf2 signaling pathway.

Objective:To investigate the protective effect and possible mechanism of sulforaphane (SFN) on acute liver injury in mice induced by diquat (DQ) poisoning.Methods:Forty-eight male C57BL/6 mice were divided into Control group, DQ model group (DQ group), SFN intervention group (DQ+SFN group), and SFN control group (SFN group) using a random number table method, with 12 mice in each group. Acute liver injury mice model was established by one-time intraperitoneal injection of 1 mL of 40 mg/kg DQ solution at once. SFN group was injected with 1 mL of ddH 2O. After 4 hours of molding, 0.5 mL of 5 mg/kg SFN solution was injected into the peritoneal cavity of the DQ+SFN group and SFN group, once daily for 7 consecutive days. DQ group and Control group were injected with an equal amount of ddH 2O. Then, the mice were euthanized to collect liver tissue and blood samples, and the levels of plasma biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as oxidative stress indicators such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in liver tissue were measured. The changes of liver structure were observed under transmission electron microscopy. The apoptosis and reactive oxygen species (ROS) level in liver tissue were observed under fluorescence microscope. Western blotting was used to detect the protein expressions of nuclear factor E2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and cleaved caspase-9 in liver tissue. Results:Compared with the Control group, the liver mitochondria in the DQ group showed severe swelling, partial dissolution of the matrix, and cristae rupture and loss; the levels of plasma AST and ALT significantly increased, the MDA content in the liver increased, the activities of SOD and GSH decreased, the level of ROS significantly increased, the number of apoptotic cells in the liver significantly increased, the protein expressions of Nrf2 and HO-1 significantly decreased, and the protein expressions of Keap1 and cleaved caspase-9 significantly increased. Compared with the DQ group, the mitochondrial damage in the DQ+SFN group was reduced, the levels of plasma AST and ALT were significantly reduced [ALT (U/L): 58.22±4.39 vs. 79.94±3.32, AST (U/L): 177.64±8.40 vs. 219.62±11.60, both P < 0.01], the liver MDA content decreased, and the activities of SOD and GSH increased [MDA (μmol/g: 5.63±0.18 vs. 5.96±0.29, SOD (kU/g): 102.05±4.01 vs. 84.34±5.34, GSH (mmol/g): 16.32±1.40 vs. 13.12±1.84, all P < 0.05], the production of ROS in liver tissue was significantly reduced [ROS (fluorescence intensity): 115.90±10.89 vs. 190.70±10.16, P < 0.05], and apoptotic cells were significantly reduced (cell apoptosis index: 4.39±1.00 vs. 10.71±0.56, P < 0.01), the protein expressions of Nrf2 and HO-1 were significantly increased, while the protein expressions of Keap1 and cleaved caspase-9 were significantly decreased (Nrf2/β-actin: 1.15±0.04 vs. 0.93±0.05, HO-1/β-actin: 1.75±0.12 vs. 0.78±0.04, Keap1/β-actin: 1.00±0.14 vs. 1.28±0.13, cleaved caspase-9/β-actin: 1.31±0.12 vs. 1.81±0.09, all P < 0.05). However, there was no statistically significant difference in various indicators between the SFN group and the Control group. Conclusion:SFN can activate the Keap1/Nrf2 signaling pathway to alleviate DQ induced acute liver injury in mice.

Objective:To investigate the impact of Adiponectin receptor agonists(AdipoRon)on renal aging induced by D-galactose(D-gal)in male C57BL/6J mice and explore potential mechanisms.Methods:Male C57BL/6J mice were randomly divided into three groups: a control group, a D-gal model group, and an AdipoRon group, each consisting of ten mice.The control group received saline through gavage and subcutaneous injection, the D-gal group received saline through gavage and D-gal through subcutaneous injection, and the AdipoRon group received AdipoRon through gavage and D-gal through subcutaneous injection.The treatment duration was eight weeks, following which blood and renal tissues were collected for testing.Kidney pathological changes were observed using Haematoxylin-Eosin(HE)staining, Masson staining, and electron microscopy.Levels of serum creatinine(SCr), urea nitrogen(BUN), and cystatin-C(Cys-C)in mice were measured using an automatic biochemical analyzer.Protein expression levels of P53, P21, P16INK4a, Silent mating-type information regulation 2 homolog 1(SIRT1), Nuclear factor E2-related factor 2(NRF2), and Klotho in renal tissues were determined through Immunohistochemical staining and Western blot.Results:The glomeruli exhibited sparse and irregular structure, with sclerosis and dilated capsular space.Renal tubules showed atrophy, while foot processes appeared fused and widened.A significant presence of blue-stained collagen fibers was noted in the renal interstitium of the D-gal group compared to the control group.Pathological damage to the kidneys was notably reduced in the AdipoRon group compared to the D-gal group.Levels of SCr(23.13±2.21 μmol/L), BUN(19.58±1.63 μmol/L), and Cys-C(0.15±0.02 μmol/L)were higher in the D-gal group than in the control group.Conversely, SCr(16.97±1.16 μmol/L), BUN(16.25±1.25 μmol/L), and Cys-C(0.12±0.01 μmol/L)levels in the AdipoRon group were lower than those in the D-gal group( F=66.61, 40.37, 48.77, all P<0.001).The expression levels of aging proteins like P53(1.68±0.11), P21(2.40±0.45), and P16INK4a(1.89±0.16)in the mice kidney tissue of the D-gal group were elevated compared to the control group.In contrast, anti-aging proteins such as SIRT1(0.46±0.04), NRF2(0.65±0.05), and Klotho(0.42±0.03)were decreased in the D-gal group versus the control group.The expression levels of aging proteins like P53(1.27±0.06), P21(1.84±0.35), and P16INK4a(1.10±0.14)in the AdipoRon group were reduced.Conversely, the expression levels of anti-aging proteins such as SIRT1(0.78±0.05), NRF2(0.87±0.07), and Klotho(0.65±0.06)were increased compared to the D-gal group( F=152.38, 44.45, 147.54, 219.69, 42.25, 166.49, all P<0.001). Conclusions:AdipoRon was found to potentially slow down D-gal-induced renal senescence in mice through activation of the SIRT1 signaling pathway.