Midazolam alleviates neuronal damage induced by oxygen glucose deprivation/restoration in mice
	    		
		   		
		   			
		   		
	    	
    	 
    	10.16352/j.issn.1001-6325.2024.04.0459
   		
        
        	
        		- VernacularTitle:咪达唑仑减轻氧糖剥夺/复糖复氧诱导的小鼠神经元损伤
 
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Tao CHEN
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Lingjun CHEN
			        		
			        		;
		        		
		        		
		        		
			        		Yuan LI
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. 永州市中心医院冷水滩院区 麻醉科,湖南 永州 425000
			        		
		        		
	        		
        		 
        	
        	
        	
        	
        		- Keywords:
        			
	        			
	        				
	        				
			        		
				        		midazolam;
			        		
			        		
			        		
				        		oxygen glucose deprivation/restoration;
			        		
			        		
			        		
				        		neuron
			        		
			        		
	        			
        			
        		
 
        	
            
            
            	- From:
	            		
	            			Basic & Clinical Medicine
	            		
	            		 2024;44(4):459-466
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
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		        	Abstract:
			       	
			       		
				        
				        	Objective To investigate the impact of midazolam on neuronal injury induced by oxygen glucose depri-vation/reoxygenation(OGD/R)in mice.Methods An injury model of neuronal cell line HT22 was established by OGD/R induction.HT22 cells were divided into OGD/R group,low-dose group,medium-dose group and high-dose group,midazolam+KG-501(CREB inhibitor)group and control group.ELISA was applied to detect TNF-α and IL-6 levels;Commercialy available reagent kits were applied to detect superoxide dismutase(SOD),catalase(CAT),and malondialdehyde(MDA)levels;MTT and Edu experiments were applied to detect cell prolifera-tion;flow cytometry was applied to detect cell apoptosis rate;RT-qPCR method was applied to detect the ex-pression levels of CREB mRNA and PGC-1α mRNA;Western blot was applied to detect the expression levels of Ki-67,Bcl-2,Bax,CREB,and PGC-1α proteins.Results Compared with the control group,the A490 value(24,48 hours),proliferation rate,SOD and CAT activity,CREB mRNA and PGC-1α mRNA expres-sion,Ki-67,Bcl-2,CREB,and PGC-1α protein level in the OGD/R group were all significantly reduced(P<0.05);The apoptosis rate,TNF-α,IL-6,MDA,and Bax protein expression were significanty increased(P<0.05).Compared with the OGD/R group,the A490 values(24,48 hours),proliferation rate,SOD,CAT activity,CREB mRNA and PGC-1α mRNA expression,and Ki-67,Bcl-2,CREB,and PGC-1α protein expression were significantly increased in low,medium,and high dose midazolam groups;The apoptosis rate,TNF-α,IL-6,MDA,and Bax protein expression were obviously reduced(P<0.05).Compared with the high-dose midazolam group,A490 value(24,48 hours),proliferation rate,activity of SOD and CAT,CREB mRNA and PGC-1α mRNA expression as well as Ki-67,Bcl-2,CREB,and PGC-1α protein expression were all sig-nificantlu reduced in the high-dose midazolam+KG-501 group while the apoptosis rate,TNF-α,IL-6,MDA,and Bax protein expression were obviously increased(P<0.05).Conclusions Midazolam might alleviate nerve cell injury potentially through the mechaninsms of promoting OGD/R-induced proliferation and reducing cell apoptosis in HT22 cells.