Research On The Preventive And Therapeutic Effect Of Babaodan On Hepatic Encephalopathy In Rats

ObjectiveTo investigate the effect of Ba Bao Dan on hepatic encephalopathy in rats with AHE/ CHE introduced by TAA/CCL4 combined TAA.The results could contribute to the effective utilization of Ba Bao Dan in the trratment of hepatic encephalopathy.MethodFifty Wistar rats were randomly divided into five groups: normal group,model group,Babaodan low-dose group(210mg/kg),Babaodan high-dose group(420mg/kg),and lactulose group(167mg/kg).All the rats were received daily gavage respectively for 7 days,and the normal and model groups were given physiological saline.On the 4th day after intragastric administration,hepatic encephalopathy was induced by intraperitoneal injection of thioacetamide(350 mg/kg),repeated after 24 h and 48 h to establish the model.Test the general condition monitoring,blood ammonia,neurological function score,serum TBil,ALT,AST,TBA,TP and Alb,pathological observation,the TNF-?,IL-1,IL-6,NF-?B,Bcl-2 and Bax genes in liver tissue,the TNF-?,IL-1,i NOS,GS in brain tissue to evaluate the effect mechanism of Babaodan on AHE.Fifty Wistar rats were randomly divided into five groups: normal group,model group,Babaodan low-dose group(210mg/kg),Babaodan high-dose group(420mg/kg),and lactulose group(167mg/kg).To establish a model of liver cirrhosis in rats,50% CCL4(1:1 ratio of olive oil)was injected intraperitoneally,twice a week for 9W.All the rats were received daily gavage respectively at 7th week,and the normal and model groups were given physiological saline.The rat model of cirrhosis ascites was successfully established.Injecting 3.5% TAA solution at a dose of 250 mg/kg and repeated once every 24 hours to lead to the heaptic encephalopathy after cirrhosis(CHE).Detecting the content of NO and TNF-? in serum and the expression of inflammation and apoptosis genes in liver tissue and brain tissue,anti-inflammatory effects of Babaodan on CHE,Western blotting detection of TLR4/My D88-NF-?B signaling pathway protein in rat liver and brain tissue,to clarify the therapeutic effects of Babaodan on HE.ResultsBabaodan can significantly inhibit the weight loss of HE rat model,reduce the blood ammonia of HE rats(p<0.05),release the serum ALT,AST,TBil,TBA,increase the content of TP and ALB,inhibit Hepatocyte necrosis,inflammatory cell infiltration,and collagen deposition in rats with cirrhosis were reduced(p<0.05).Babaodan significantly inhibited the levels of serum TNF-? and NO(p<0.05),inhibited the expression of inflammatory mediators,and down-regulated TNF-?,IL-1,IL-6,NF-?B,Bax(p<0.05),increased Bcl-2 levels(p<0.05)in liver tissues of AHE rats.inhibited IL-1,TNF-?,i NOS and GS m RNA levels in brain tissue of AHE rats(p<0.05);Babaodan can reduce the levels of TNF-?,IL-6,NF-?B,TLR4,My D88,Bax,?-SMA and Collenge m RNA in liver tissues of CHE rats(p<0.05);reduced TNF-?,IL-6,Caspase-8,NF-? B TLR4 and My D88 in brain tissue of CHE rats(p<0.05);at the same time,Babaodan can reduce TLR4/My D88-NF-?B signaling pathway related proteins and reduce the release of inflammatory factors.Conclusion(1)Babaodan can significantly attenuated HE-induced body weight loss,improve cognition,improve liver function,inhibit hepatocyte necrosis,inflammatory cell infiltration,reduce collagen deposition in liver tissue and inflammation both in liver tissue and brain tissue in rats.Therefore,Babaodan could alleviate the severity of hepatic encephalopathy models.(2)Babaodan reduced the severity of HE model may via the regulation of TLR4/My D88-NF-?B signaling pathway to supress the inflammatory response,to control the metabolism of ammonia,and play an important role in the prevention and treatment of hepatic encephalopathy.