1.Effects of exendin-4 on GFAP and IL-1βexpression in hippocampi of aged rats
Liang ZHANG ; Su MIN ; Ping LI ; Feng LYU ; Xuechao HAO ; Fei XIE ; Qibin CHEN ; Li LIU ; Yiwei SHEN ; Xianlin ZHU ; Ke WEI ; Jing CHEN
Chinese Journal of Anesthesiology 2014;(3):293-296
Objective To evaluate the effects of exendin-4 on glial brillary acidic protein (GFAP ) and interleukin-1β(IL-1β) expression in hippocampi of aged rats .Methods Forty-eight healthy male Sprague-Dawley rats ,aged 22-24 weeks ,weighing 500-700 g ,were randomly divided into 4 groups (n=12 each) using a random number table:control group (group C ) ,exendin-4 group (group E ) ,operation group (group O ) and exendin-4 plus operation group (group OE) .The rats were anesthetized with intraperitoneal fentanyl and droperidol .Groups C and E did not receive anesthesia or splenectomy .In O and OE groups ,splenectomy was carried out .In E and OE groups , exendin-4 5 μg/kg was injected intraperitoneally at 30 min before skin incision and 12 h after operation .C and O groups received the equal volume of normal saline instead of exendin-4 .Learning and memory function was assessed using Morris water maze test (escape latency (EL) and total swimming distance (TSD) at 1 day before operation (T0 ) .The fasting blood glucose was measured after anesthesia (T1 ) ,at the end of operation (T2 ) and on postoperative day 1 (T3 ) .The rats were sacrificed after assessment of the cognitive function at T 3 and the hippocampi were removed for determination of the expression of GFAP (by immuno-histochemistry ) and IL-1β(by Western blot ) .Results There was no significant difference in the EL and TSD at T0 between the four groups ( P>0.05) .Compared with group C ,the EL and TSD were significantly prolonged at T3 and fasting blood glucose was increased at T2 ,3 ,and the expression of IL-1βand GFAP was up-regulated at T3 in O and OE groups ( P<0.05) .Compared with group O ,the EL and TSD were significantly prolonged at T3 and fasting blood glucose was decreased at T2 ,3 ,and the expression of IL-1βand GFAP was down-regulated at T3 in group OE ( P<0.05) . Conclusion Exendin-4 can improve the postoperative cognitive function of aged rats by inhibiting inflammatory responses in hippocampi and maintaining stable perioperative blood glucose .
2.Effect of Salmon Calcitonin on Osteoporosis Induced by Spinal Cord Injury
Jun LI ; Liangjie DU ; Hongwei LIU ; Tianjian ZHOU ; Xuechao DONG ; Weijiao FAN ; Yun GUO ; Chong WANG ; Feng GAO ; Degang YANG ; Liang CHEN ; Mingliang YANG
Chinese Journal of Rehabilitation Theory and Practice 2015;21(8):953-956
Objective To explore the effect of salmon calcitonin on osteoporosis induced by spinal cord injury. Methods 100 patients with osteoporosis induced by spinal cord injury from September 2011 to September 2014 in our department were included. They were randomly divided into control group (n=50) and observation group (n=50). The control group received vitamin D3 only, while the observation group received vitamin D3 combined with salmon calcitonin on the basis of rehabilitation physiotherapy, for 6 months. Visual Analogue Scale (VAS) of pain was evaluated in different periods. The bone mineral density (BMD) of lumbar spine and femoral neck, the parathyroid hormone (PTH), bone gla protein (BGP) and 1,25- dihydroxy vitamin D3 (1,25-(OH)2D3) were tested and recorded. Results The VAS score was lower in the observation group than in the control group 1, 2, 3 and 6 months after treatment (P<0.001). The BMD of lumbar spine and femoral neck was significantly higher, the PTH and BGP were significantly lower and the 1,25-(OH)2D3 was significantly higher in the observation group than in the control group after treatment (P<0.001). Conclusion Combination of salmon calcitonin can effectively reduce the bone pain and improve the BMD in patients with osteoporosis induced by spinal cord injury.
3.Mechanism of traditional Chinese medicine Bai Zhi in preventing microgravity induced bone loss based on network pharmacology and transcriptomics
Xuechao LIANG ; Ye TIAN ; Kang RU ; Bo SANG ; Rui LIANG ; Airong QIAN
Space Medicine & Medical Engineering 2024;35(4):228-234
Objective In this study,we investigated the active ingredients,targets and molecular mechanisms of Bai zhi based on network pharmacology and mRNA transcriptome sequencing technology for the treatment of microgravity induced bone loss,with a view to providing new therapeutic strategies for microgravity induced bone loss diseases.Methods Investigating the antagonistic effect of the traditional Chinese medicine Bai zhi on microgravity induced bone loss by constructing a hindlimb unloading mice model.18 healthy male mice were randomly divided into Control,HLU and HLU+BZ groups,6 mice in each group,and the effects of Bai zhi on the bone mineral density of the model mice were evaluated after 28 d of continuous gavage.Screening the active ingredients and targets of Bai zhi through TCMSP,Genecards,OMIM,TTD,DisGeNET and other network pharmacology databases.A hindlimb tail suspension unloading animal(HLU)model was established,and the differentially expressed genes(DEGs)responding to mechanical unloading were analyzed using transcriptome sequencing methods,and the targets of Bai zhi active ingredients intersected with the targets of the differentially expressed genes responding to mechanical unloading,so that the core gene targets of Bai zhi for intervening in weightlessness bone loss could be obtained;Construction of Bai zhi component-target protein interaction network(PPI)using String database and Cytoscape software,and enrichment and analysis of key signaling pathways of Bai zhi for treating microgravity induced bone loss using R Studio software.Results Bai zhi effectively restored bone loss in hindlimb tail suspension mice.By quantitative analysis of bone mineral density scanning of hindlimb tail suspension mice,the results showed that Bai zhi significantly restored the loss of bone mineral density in the model mice(P?0.001),Bai zhi has obvious improvement effect on mirogravity induced mice bone loss.10 kinds of Bai zhi effective active ingredients were obtained through the network pharmacology database screening,306 components of the action target,1751 osteoporosis-related disease targets,and 33 disease drug common targets were obtained by drawing the intersection of Wayne's diagram calculation.Through target intersection with transcriptome sequencing differentially expressed genes under simulated microgravity conditions,32 core genes of Bai zhi for intervening in microgravity induced bone loss were obtained,including nuclear transcription factor(JUN),Toll-like receptor 4(TLR4),capsaicin receptor(TRPV1),and so on;Enrichment analysis of the 32 core genes was performed,and the results of GO functional enrichment analysis showed that a total of 194 GO terms were obtained,including 123 biological process(BP)terms,which mainly included insulin-like growth factor receptor,glucose homeostasis in vivo,and negative regulation of gene expression;28 Molecular Function(MF)terms,including RNA polymerase II transcription factor activity,ligand-activated sequence-specific DNA binding,and transcription factor binding;there were 43 cellular component(CC)terms,including cytoplasmic membrane,receptor complex,euchromatin,etc.The results of KEGG enrichment analysis indicated that Bai zhi may be involved in the regulation of insulin-like factor,HIF-1 hypoxic stress,AMPK and other signaling pathways to play a therapeutic function for microgravity induced bone loss.Conclusion under simulated microgravity conditions,the effective active ingredients of Bai zhi may inhibit the accumulation of glycosylation end products(AGEs),oxidative stress damage,and the production of inflammatory factors induced by microgravity stress by regulating the expression of differential genes in response to mechanical unloading,and then participate in osteoblast differentiation in the bone microenvironment to alleviate the occurrence of microgravity induced bone loss diseases.