1.Role of JNK signaling pathway in paclitaxel-induced apoptosis in hippocampal neurons of rats: the relationship with NF-κB pathway
Chuan WU ; Xiaoxiao CHAI ; Xiuli WANG ; Shuang ZHAO ; Zi JIN ; Zhao LI ; Yuexian GUO
Chinese Journal of Anesthesiology 2015;35(11):1347-1349
Objective To evaluate the role of c-Jun N-terminal kinase (JNK) signaling pathway in paclitaxel-induced apoptosis in hippocampal neurons of rats, and the relationship with nuclear factor kappa B (NF-κB) pathway.Methods The primarily cultured hippocampal neurons were seeded in 96-well plate at a density of 1×106 cells/ml (200 μl/hole) , and were randomly divided into 4 groups (n=8 each) using a random number table: control group (C group), paclitaxel group (P group), JNK inhibitor SP600125 group (S group), and SP600125 + paclitaxel group (S+P group).Paclitaxel 2 ml (1 μmol/L) was added to group P.SP600125 2 ml (10 μmol/L) was added to group S.In group S+P, SP600125 2 ml (10 μmol/L) was added, the cell were then incubated for 1 h, and then paclitaxel 2 ml (1 μmol/L) was added.The cells were then incubated for 24 h.At 24 h of incubation, the apoptosis in hippocampal neurons was detected by flow cytometry, and the expression of NF-κB p65 was measured by Western blot.The apoptosis rate was calculated.Results Compared with group C, the apoptosis rate was significantly increased, and the expression of NF-κB p65 was up-regulated in P and S+P groups, and the apoptosis rate was significantly decreased, and the expression of NF-κB p65 was down-regulated in group S (P<0.05).Compared with group P, the apoptosis rate was significantly decreased, and the expression of NF-κB p65 was down-regulated in group S+P (P<0.05).Conclusion JNK signaling pathway mediates paclitaxel-induced apoptosis in hippocampal neurons of rats, and the mechanism is likely related to inhibition of NF-κB pathway activation.
2.Role of autophagy in pancreatic injury in sepsis
Yuexian LI ; Liangyuan SUO ; Jin ZHANG
Chinese Critical Care Medicine 2020;32(4):504-507
Sepsis is a life-threatening systemic inflammatory response syndrome (SIRS) caused by the host's maladjustment response to infection, which eventually leads to septic shock and multiple organ failure. Pancreatic injury was found to be an important pathological change in sepsis. Autophagy is a crucial way to maintain the normal metabolism of cell substances and energy, which plays an important role in many diseases. Recent studies have found that autophagy plays a dual role in pancreatic injury in sepsis. Moderate autophagy can protect the pancreas and reduce the injury, while excessive autophagy can cause apoptosis-related autophagic cell death and aggravate the pancreatic injury. In sepsis, activated nuclear factor-κB (NF-κB) has a promoting effect on autophagy, and lysosome associated membrane protein (LAMP) degradation can result in impaired autophagy flux and aggravate pancreatic injury. The exploration of the mechanism of autophagy in pancreatic injury of sepsis will help to restore the normal autophagy function, so as to find a new target for the treatment of pancreatic injury of sepsis.
3.Effect of Sodium Pyrosulfite Solution Soaking on Flavonoids in Astragali Radix
Yuexian JIN ; Nailiang ZHU ; Dan ZHAO ; Rui WANG ; Guoxu MA ; Xudong XU
China Pharmacist 2018;21(10):1747-1750
Objective: To analyze the contents of flavonoids in Astragali Radix before and after sodium pyrosulfite solution soa-king, so as to provide reliable methods for scientifically evaluating and effectively controlling the quality of Astragali Radix. Methods:After sodium pyrosulfite solution soaking, the contents of calycosin glucoside, ononin, formononetin and pterostilbene were analyzed by HPLC-DAD. Results: Calycosin glucoside, ononin, formononetin and pterostilbene showed a good linear relationship within the range of 0. 048-60. 000 μg·ml-1, 0. 019-30. 000 μg·ml-1, 0. 019-40. 000 μg·ml-1and 0. 019-40. 00 0μg·ml-1, respectively. After sodium pyrosulfite solution soaking, the contents of calycosin glucoside and ononin decreased, furthermore, with the increase of sodium sulfite solution concentration and soaking time, the decrease trend was more obvious, and the differences between the high concentra-tion group and the normal group were 2-3 times. The content of formononetin was essentially the same, while the difference in pterostil-bene content between the high concentration groups and the normal group was 10 times. Conclusion: After sodium pyrosulfite solution soaking, the contents of flavonoid glycoside components are reduced, therefore, it is not advisable to use sodium pyrosulfite solution soaking to achieve keeping fresh, mothproof and prolonging the shelf life of Astragali Radix.
4.Impacts of andrographolide on sciatic nerve function damage in diabetic peripheral neuropathy rats by regulating HMGB1/RAGE signaling pathway
Yuexian SUN ; Jiumei WANG ; Xingang CUI ; Jin YU
China Pharmacy 2024;35(5):572-577
OBJECTIVE To investigate the impacts of andrographolide on sciatic nerve function injury in diabetic peripheral neuropathy (DPN) rats by regulating high-mobility group protein box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) signal pathway. METHODS A total of 84 rats were randomly divided into the control group (normal saline), DPN group (normal saline), low-dose andrographolide group (0.833 mg/kg), high-dose andrographolide group (3.332 mg/kg), lipoic acid group (positive control, 0.1 g/kg), recombinant rat HMGB1 protein (rHMGB1) group (8 μg/kg), and high-dose andrographolide+ rHMGB1 group, with 12 rats in each group. All rats except those in the control group were fed with high glucose and high fat diet combined with intraperitoneal injections of streptozotocin to establish the DPN rat model. After 24 hours of successful modeling, medication was administered daily for 8 weeks. The changes in fasting blood glucose, mechanical pain threshold, heat pain threshold and sciatic nerve conduction velocity were detected. Pathological changes in the sciatic nerve of rats and the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the sciatic nerve of rats were also detected. Besides, the expressions of HMGB1, RAGE proteins and phosphorylation level of nuclear factor κB p65(NF-κB p65) protein in rat sciatic nerves were found. RESULTS Compared with the control group, the pathological damage of the sciatic nerve of rats in the DPN group was strengthened, the fasting blood glucose, heat pain threshold, MDA content and the 诊治。E-mail:dqiaur@163.com expressions of HMGB1, RAGE proteins and phosphorylation level of NF-κB p65 protein were increased (P<0.05), while the mechanical pain threshold, sensory nerve conduction velocity, motor nerve conduction velocity, and SOD activity were decreased/slowed down (P<0.05). Compared with the DPN group, the above indexes were significantly potentiated in the andrographolide low- and high-dose groups and lipoic acid group (P<0.05), and the corresponding trends in the rHMGB1 group were opposite to those in the above three administration groups (P<0.05). Moreover, rHMGB1 attenuated the hypoglycemic effect of high-dose andrographolide on blood glucose and the improvement of oxidative stress injury in the sciatic nerve of DPN rats (P<0.05). CONCLUSIONS Andrographolide may reduce blood glucose by inhibiting the HMGB1/RAGE pathway and oxidative stress, thus ameliorating sciatic nerve injury in DPN rats.