Study On Therapeutic Effect And Mechanism Of Dihydromyricetin On Thioacetamide Induced Hepatic Encephalopathy Associated With Fulminant Hepatic Failure Model In Mice

Purpose:To investigate the effect and mechanism of dihydromyricetin (DMY) on thioac-etamide (TAA) induced hepatic encephalopathy (HE) associated with fulminant hepatic failure (FHF) model in mice.Methods:40 male Balb/c mice were randomly assigned into four groups of 10 mice.:group A(normal control), group B(DMY group), group C(model group or TAA group), and group D (treatment group or DMY+TAA group).First day, sterile normal saline solution was injected to group A by the intraperitoneal (i.p.) route as a single dose of 10ml/kg;DMY dissolved in sterile dd-water was inject to group B by the i.p. route as a single dose of 5mg/kg; TAA dissolved in sterile normal saline solution was injected to C and D group by the i.p. route as a single dose of 600 mg/kg. Twenty-four hours later all animals were injected (subcutaneously) with 0.5 mL solution of 0.45% NaCl,5% dextrose and 0.2% KCl in order to prevent hypovolemia, hypokalemia and hypoglycemia. Assessment of neurological function and activity in this time, to remove modeling unsuccessful mouse. Next, sterile normal saline solution was injected to group C by the i.p. route as a single dose of 10ml/kg;DMY dissolved in sterile dd-water was inject to group D by the i.p. route as a single dose of 5mg/kg.Third day, Assessment of neurological function and activity of all animals. The blood was got from the fundus oculi vein of mouse in order to examine ammonia、ALT、AST、TBIL and ALB. Then the rats were put to death with the cervical dislocation,After which brains and livers were removed for histopathological analysis and brains immunohistochemical detection of glial fibrillary acidic protein (GFAP),The expression of NF-κB cells was determined by the Western blotting(WB). All data are expressed as mean ±standard error of the mean, Comparison between groups of data were performed using T-test. P< 0.05 statistically significant.Result:Compared with normal control group:In a thioacetamide-induced hepatic encephalopathy associated with fulminant hepatic failure mouse, (1) poorer neurological function (0.30±0.12 vs 3.90±0.74)、less activities (30.40±2.55 vs 19.70±1.57),there were significant differences(P<0.01); (2) in plasma levels of the hepatic enzymes, ALT (66.43±18.67 vs 224.80±27.83)、AST (110.82±30.68 vs 488.47±47.92) and TBIL (1.77±0.36 vs 5.23±0.65) raised significantly, there were significant differences(P<0.001);(3) severe liver injury pathological(0 vs 34.53%±4.26%, P<0.001); (4) the expression of positive GFAP went up in hippocampus (36.30±3.43 vs 48.20±2.62, P<0.01); (5) the expression of NF-κB went up in hippocampus (P<0.01). Compared with TAA group:(1)DMY had a neuroprotective effect in this animal model as shown by the neurological score (3.90±0.74 vs 1.80±0.79) and activity function (19.70±1.57 vs 25.40±1.17),there were significant differences(P<0.01); (2) DMY lowered content of ALT (224.80±27.83 vs 145.31±12.88)、AST (488.47±47.92 vs 309.51±25.92) and TBIL (5.23±0.65 vs 3.31±0.35), there were significant differences(P<0.001);(3) DMY improved severe liver injury pathological (34.53%±4.26% vs 26.66%±4.76%、P<0.01);(4) DMY reduced expression of positive GFAP(48.20±2.62 vs 41.10±1.66, P<0.01);(5) DMY reduced expression of NF-KB (P<0.05)Conclusions:(1)DMY improves brain and liver function in a thioacetamide-induced HE associated with FHF model in Balb/c mice;(2) It may be the mechanism that DMY improves liver function,ameliorates astrogliosis and expression of NF-κB.