Fufangjiakang Film Of Hyperthyroidism With Liver Damage In Rats And Its Action Mechanism

ObjectiveTo study relevance mechanism of Fufangjiakang tablet protecting and treating hyperthyroidism with liver damage,and enhance recognizing mechanism of hyperthyroidism with liver damage,and provide treatment based on clinical safety, through treating the hyperthyroid rat model with liver damage by Fufangjiakang tablet.MethodsThrough choosing 98 health Wistar rats,weight about 120±15g,male and female (half and half),choosing 20 cases as a control group randomly after raising the 98 rats one adaptable week.The control group given every morning to feed 2ml distilled water.Choosing 20 cases as mild hyperthyroidism randomly,which were gavaged for 2ml of the concentration of 50μg/ml of L-T₄ tablet daily,the low volume group of the model.The remaining 58 rats as severe Hyperthyroidism,which were gavaged for 2ml of the concentration of 100μg/ml of L-T₄ tablet daily,the high volume of the model.The three groups were gavaged for 28 days continuously.The 29th day(that is, the fourth week),10 rats were choossed from the control group,the low volume group of the model,the high volume group of the model separately,and the indicators of FT₃,FT₄,TSH and ALT,AST,r-GT,ALP,TP,ALB,GLB,TBil,DBil,IBil were tested and observed pathological frame.After that,then another 48 severe hyperthyroid rats were randomly divided into four groups,namely the high volume group of the model,thiamazole group,pure traditional chinese drug group,the Fufangjiakang tablet group,12 rats each group. Since the 29th day,the three group,namely the control group,the low volume group of the model,the high volume group of the model,were keeping the former methods every morning,In addition,the three group were gavaged for 2ml distilled water,the thiamazole group with 2ml solution of thiamazole,pure traditional chinese drug group with 2ml solution of pure traditional chinese drug,the Fufangjiakang tablet group with 2ml solution of Fufangjiakang tablets in water,every afternoon.Do that for 32 days continuously.After the experiment,collect relevant specimens,and test FT₃,FT₄,TSH by RIA, test ALT,AST,r-GT,ALP,TP,ALB,GLB,TBil,DBil,IBil by automatic biochemical analyzer,detect volume of MDA by phosphorothioate acid fluorescence, test SOD activity by xanthine oxidase enzyme,GSH-Px activity by disulfide pairs nitrobenzoic acid,Na⁺-K⁺-ATPase activity by phosphorus determination,observe structure of the liver by light microscopy and electron microscopy separately,detect FasL,Fas,TNF-αby immunohistochemical method(SP),and detect T₃Rα1,T₃Rβ1 gene expression by RT-PCR.Results1.The weight were significantly increased,but were slow in the model group.The 4th week,the three groups were significant differences(P＜0.05),the high volume group of the model with the control group was a very significant difference(P＜0.01).The 8th week,the former three groups were the same of the 4th week.The treatment groups had increased the weight in rats,and the treatment groups with the high volume group of the model were significant differences(P＜0.05),and the Fufangjiakang tablet group and the thiamazole group were better than the pure traditional chinese drug group.2.The volume of food,drink,and excretion were significantly increased,but were slow in the control group.The 4th week,the model groups with the control group were significant differences (P＜0.05),the high volume group of the model with the low volume group of the model was no significant difference(P＞0.05).The 8th week,they were the most volume in the low volume group of the model. The former three groups were the same of the 4th week.They had reduced in the treatment groups.The treatment groups with the high volume group of the model were significant differences(P＜0.05),and the Fufangjiakang tablet group and the pure traditional chinese drug group were better than the thiamazole group.3.The changes of FT₃,FT₄,TSH.The 4th week,FT₃,FT₄ increasing,TSH lowering,the model groups with the control group were significant differences(P＜0.05),the high volume group of the model with the control group was a very significant difference(P＜0.01).The 8th week,by vertically contrast,FT₃,FT₄ continue to rise and TSH keep lowering,there were significant differences(P＜0.05)in the low volume of the model and no significant difference(P＞0.05)in the control group and the high volume group of the model by vertically contrast with the fourth week of the group on its own.The 8th week,by horizontal contrast,FT₃,FT₄ lowering,TSH increasing,in the treatment groups.The treatment groups with the high volume group of the model were significant differences(P＜0.05).By contrast of effect of their treatment, thiamazole group＞Fufangjiakang tablets group＞pure traditional chinese drug group.4.The changes of Indicators of liver function.They,GLB,TBil,DBil,IBil each group,were no significant difference(P＞0.05).The 4th week,ALT,AST,r-GT,ALP increasing,TP,ALB lowering,the model groups with the control group were significant differences(P＜0.05),the low volume group of the model with the high volume group of the model was no significant difference(P＞0.05).The 8th week,by vertically contrast,ALT,AST,r-GT,ALP continue to rise,there were significant differences(P＜0.05)in the model group.But TP,ALB keep lowering, there were significant differences(P＜0.05)in the high volume group of the model.The 8th week,by horizontal contrast,ALT,AST,r-GT,ALP increasing,there were significant differences(P＜0.05)in the former three group.The high volume group of the model with control group was a very significant differences(P＜0.05).But TP, ALB keep lowering,there were significant differences(P＜0.05)in the high volume group of the model.ALT,AST,r-GT,ALP lowering in the treatment groups,The high volume group of the model with the treatment groups was a very significant differences(P＜0.05).By contrast of effect of their treatment,Fufangjiakang tablets group＞pure traditional chinese drug group＞thiamazole group.TP,ALB increasing in the treatment groups,By contrast of effect of their treatment,Fufangjiakang tablets group was better than pure traditional chinese drug group and thiamazole group.5.The changes of structure of liver by light microscopy.Its structure was normal in the control group.There were,in the low volume group of the model,mainly hepatocyte mild swelling,cytoplasm sparse,central venous congestive,sinusoid expanding,point necrosis in central,neutrophil and lymphocyte penetrating in portal area.In addition,there were,in the high volume group of the model,swelling of the hepatocyte obviously,or fatty drop,disorder of the cable of the hepatocyte,point of scattered necrosis in the hepatic lobule.There were,in the thiamazole group,improvements to reduce swelling of the liver, expanding of bile duct.There were,in the pure traditional chinese drug group, reducing swelling of the hepatocyte and expansion of sinusoid and congestion of the central vein.There were,in the Fufangjiakang tablet group,reducing swelling of the hepatocyte and expansion of sinusoid and congestion of the central vein significantly. The dual-core cells increased in the Fufangjiakang tablet group.6.The changes of structure of liver by electron microscopy.Its ultrastructure was normal in the control group.There were,in the low volume group of the model,reducing of glycogen granules,and rich expansion RER.There were increased mitochondria,fractured ridge,different shape,expansion of sinusoid and capillary duct,reducing of the microvilli in the low volume group of the model. In addition,there were increased mitochondria,disorder ridge or disappeared,fatty drops vacuoles,or chromatin condensation,and cell necrosis.There were,in the thiamazole group,markedly increased glycogen granules, reducing number of mitochondrial,swelling of mitochondrial and expansion of capillary duct and congestion of cholestasis,or necrosis.There were,in the pure traditional chinese drug group,increased glycogen granules,reducing number of mitochondrial and swelling of mitochondrial,reducing expansion of capillary duct. There were,in the Fufangjiakang tablet group,increased glycogen granules,reducing number of mitochondrial and swelling of mitochondrial,order ridge,prolifered endoplasmic reticulum significantly.7.The changes of Na⁺-K⁺-ATPase,GSH-Px,SOD,MDA.Na⁺-K⁺-ATPase activity increased in the low volume group of the model and lowered in the low volume group of the model.The former groups were significant differences(P＜0.05),the low volume group of the model with the control group was a very significant difference(P＜0.01).Na⁺-K⁺-ATPase activity increased in the treatment groups.The treatment groups with the high volume group of the model were significant differences(P＜0.05).By contrast of effect of their treatment, Fufangjiakang tablets group＞pure traditional chinese drug group＞thiamazole group.GSH-Px,SOD activity lowered in the model groups.The former groups were significant differences(P＜0.05),the high volume group of the model with the control group was a very significant difference(P＜0.01).GSH-Px,SOD activity increased in the treatment groups.The treatment groups with the high volume group of the model were significant differences(P＜0.05).The Fufangjiakang tablet group with the high volume group of the model was a very significant differences(P＜0.01).By contrast of effect of their treatment,Fufangjiakang tablets group＞pure traditional chinese drug group＞thiamazole group.MDA increased in the model groups.The former groups were significant differences(P＜0.05),the high volume group of the model with the control group was a very significant difference(P＜0.01).MDA lowered in the treatment groups.The treatment groups with the high volume group of the model were significant differences(P＜0.05).The Fufangjiakang tablet group with the high volume group of the model was a very significant differences(P＜0.01).By contrast of effect of their treatment,Fufangjiakang tablets group＞pure traditional chinese drug group＞thiamazole group.8.The changes of FasL,Fas,TNFα.FasL,Fas,TNFαincreased in the model groups.The former groups were significant differences(P＜0.05),the high volume group of the model with the control group was a very significant difference(P＜0.01).FasL,Fas,TNFαlowered in the treatment groups.The treatment groups with the high volume group of the model were significant differences(P＜0.05).The Fufangjiakang tablet group with the high volume group of the model was a very significant differences(P＜0.01).By contrast of effect of their treatment,Fufangjiakang tablets group was better than pure traditional chinese drug group and thiamazole group.9.The changes of T₃Rα1,T₃Rβ1 mRNA.It,T₃Rβ1 mRNA,was no significant difference(P＞0.05)each group.T₃Rα1 mRNA increased in the model groups.The former groups were significant differences (P＜0.05),the high volume group of the model with the control group was a very significant difference(P＜0.01).T₃Rα1 mRNA lowered in the treatment groups.The treatment groups with the high volume group of the model were very significant differences(P＜0.01).The Fufangjiakang tablet group and thiamazole group with the pure traditional chinese drug group were significant differences(P＜0.05).By contrast of effect of their treatment,the Fufangjiakang tablet group and the thiamazole group were better than the pure traditional chinese drug group.Conclusion1.Features of hyperthyroidism combined liver damage.Its the extent liver damage is related to the thyroid hormone level,the course.The higher the level of thyroid hormone is and the longer the course is,the sooner the time of liver damage emerge and the more serious degree is.2.Treatment mechanism of Fufangjiakang tablet.It,mechanism of treat hyperthyroidism combined liver damage by Fufangjiakang tablets,reduces the level of thyroid hormone,improve liver metabolism,might enhance the removal of the body of oxygen free radicals,and reduce the concentration of damage cytokines,and reduce expression of liver nuclear receptor gene,promote hepatocyte to recover.They realize effect of prevention and treatment of hyperthyroidism and protection of liver.3.Effect of Fufangjiakang tablets.It,effect of prevention and treatment of hyperthyroidism and protection of hyperthyroidism combined liver damage by Fufangjiakang tablet,is better than single thiamazole or single pure traditional chinese drug.4.Advantage of Fufangjiakang tablets.It,advantage of prevention and treatment of hyperthyroidism and protection of hyperthyroidism combined liver damage by Fufangjiakang tablet,reduces dosage and the side effects of western medicine,might reduce the other complications of hyperthyroidism,promote the recovery of hyperthyroidism and hyperthyroidism with liver damage.