Discussion On The Efficacy And Mechanism Of Seaweed Yuhu Decoction With High-dose Licorice And Different Kinds Of Seaweed

Backgrounds:Eighteen antagonistic medicaments belong to the incompatibility of traditional Chinese medicine,including Sargassum(Haizao,HZ)and Radix Rhizoma Glycyrrhizae(Gancao,GC),which are a pair of antagonistic medicaments.Unlike other antagonistic medicaments,both HZ and GC are non-toxic.Modern studies have shown that there are differences in chemical constituents and pharmacological effects between Haihaozi and Yangqicai.There are many literatures about the co-use of GC and HZ in the past dynasties.There are also many reports on the treatment of related diseases with the antagonistic medicaments in modern clinical applications.The combination of HZ and GC is mostly used in compound prescriptions in clinic,and in pathological conditions,whether it will have side effect.Haizao Yuhu Decoction is a classic prescription containing HZ and GC,which is mainly used to treat goiter and other diseases.Previous research results of our group found that the combined use of HZ(Haihaozi,Yangqicai)and GC in the treatment group of goiter model rats induced by propylthiouracil(PTU)had different therapeutic effects on goiter in goiter model rats under the dosage limit of 5 times prescribed in the Chinese Pharmacopoeia.The antagonistic medicaments in the Incompatibility of traditional Chinese medicine can be manifested not only in the toxicity of compatibility application,such as impairment of heart,liver and kidney function,but also in the weakening of drug treatment effect caused by compatibility application.Therefore,at this dose,whether the difference of therapeutic effect of Haizao Yuhu Decoction on goiter rats is related to different HZ varieties or antagonistic medicaments and its mechanism need to be further explored.Objects:The expression of TPO and Tg in rat thyroid tissue was detected.To explore the Effects of adding or subtracting antagonistic medicaments on thyroid hormone synthesis in rats goiter by Haizao Yuhu Decoction which containing the the different HZ varieties and GC in prescribed dosage of 5 times as high as the prescribed dosage in the Chinese Pharmacopoeia.To detect the expression of Bax and Bcl-2 mRNA in thyroid tissue and explore the related mechanism of apoptosis of thyroid cells.Methods:Pharmacodynamic effect:After weighing,rats were randomly divided into 9 groups according to their weight:blank group,model group,positive drug group,Haizao Yuhu Decoction with Haihaozi(HYD Haithaozi)group,Haizao Yuhu Decoction with Haihaozi without GC(HYDHaihaozi-GC)group,Haizao Yuhu Decoction with Yangqicai(HYD Yangqicai)group,Haizao Yuhu Decoction with Yangqicai without GC(HYDYagqicai-GC)group,Haizao Yuhu Decoction without HZ(HYD-HZ)group,Haizao Yuhu Decoction without HZ and GC(HYD-HZ-GC)group,16rats in each group.During the modeling period,except for the blank group,the other groups of rats were given PTU10mg/kg once a day for14 days.The drug was administered after modeling,and the cycle was 28 days.The blank group and the model group were given the same amount of distilled water for gavage.Positive drug group was given the Levothyroxin Sodium Tablets,the dose was 20?g/kg,once a day.The other administration groups were intragastrically administered with the corresponding drug solution,and the rats were administered once a day at a dose of 13.5g/kg for HYDHaihaozi-GC group and HYDYangqicai-GC group,12.6g/kg for HYD-HZ group.HYDHaihaozi group and HYDYangqicai group were 18.0g/kg.It was 8.1 g/kg in HYD-HZ-GC group.In order to stabilize the model of goiter in rats,PTU was administered every other day except the blank group.At the end of administration,the thyroid coefficient of each group was calculated,the histopathological morphology of rat thyroid was observed,and the thyroid function was detected.To observe the effect of different HZ varieties and GC on the pharmacodynamics of goiter rats under the dosage limit of 5 times prescribed in Chinese Pharmacopoeia.Mechanisms:To detect the gene expression of TPO and Tg mRNA in thyroid tissue,to explore the mechanism of the effect of different HZ varieties and GC in Haizao Yuhu Decoction containing 5 times the prescribed dose in Chinese Pharmacopoeia on thyroid hormone synthesis in goiter rats,to detect the expression of Bax and Bcl-2 mRNA in thyroid tissue,and to explore the related mechanism of apoptosis of thyroid cells.Result:1 Effects of GC and different species of HZ in Haizao Yuhu Decoction Containing high-dose antagonistic medicaments with or without HZ GC on the Pharmacodynamic effect of goiter in rats:Firstly,the goiter model was duplicated.Compared with the blank group,the serum levels of T4,FT3 and FT4 in the model group were significantly lower,the TSH level was significantly higher.Thyroid tissue lobules arranged disorderly,the structure of lobules was blurred,thyroid follicular epithelial cells diffuse hyperplasia and hypertrophy,thyroid follicles were not uniform in size,follicular endocrine was reduced.The body weight and Anal temperature of the model rats were lower than those of the blank group.The rats showed a low metabolic state.They liked to accumulate and reacted slowly,suggesting that the model was successfully replicated.After treatment,the positive drug treatment group corrected the hypometabolic state caused by the decrease of thyroid hormone in rats,reversed the decreased body weight,Anal temperature and serum T4,FT4,TSH levels,but did not improve the thyroid coefficient and histological structure.There was no significant effect on body weight,anal temperature,serum T4,FT3 and FT4 water of model rats by adding or subtracting antagonistic medicaments in Haizao Yuhu Decoction.Compared with the model group,the serum TBG levels in rats with HYD Haihaozi-GC group,HYDYangqicai group,HTD-HZ group and HYD-HZ-GC group increased.The serum TRH of HYD Haihaozi-GC group and HYDYangqicai group rats was higher than that of blank group.The levels of TPO and Tg in serum of rats in each group were not significantly different,but the goiter was significantly improved,including thyroid coefficient,histological structure and morphology.2 Mechanism discussion2.1 Effects on Thyroid Hormone Synthesis Related Genes:The expression of TPO and Tg in thyroid tissue of rats in model group decreased,but there was no significant difference in the expression of Tg.HYDY angqicai-GC group inhibited the expression of Tg mRN A in rat thyroid tissue.HYDHaihaozi-GC group corrected the inhibitory effect of PTU on TPO gene expression,while HYDy angqicai-GC group did not.In promoting TPO gene expression,the effect of HYDHaihaozi-GC group was better than that of HYDYangqicai-GC group.There was no significant difference between the effect of HYDHaihaozi group and that of HYDYangqicai group.HYDYangqicai-GC group inhibited the expression of TPO and Tg genes.2.2Effect on apoptosis of thyroid cells:Compared with the blank group,the expression level of Bax mRNA and Bax/Bcl-2in the model group decreased.HYDHaihaozi group,HYDHaihaozi-GC group,HYDYangqicai group,HYDyangqicai-GC group,HYD-HZ group and HYD-HZ-GC group could increase the expression of Bax gene,but had no effect on the expression of Bcl-2gene.Bax/Bcl-2 increased.Conclusion:1 There was no significant improvement on the decrease of thyroid hormone level caused by PTU modeling in each group with the antagonistic medicaments of different HZ varieties and GC antibiotics at a high dose of 5 times prescribed in the Chinese Pharmacopoeia,but there was a call-back effect on TSH.The possible mechanism was the expression of TPO and Tg mRINA.When Yangqicai was used and removed GC in the compound prescription,the expression of TPO and Tg mRNA had a certain inhibitory effect.Compared Yangqicai alone with Yangqicai and GC compatibility and Haihaozi,Yangqicai alone had poor effect.2The treatment of goiter including thyroid coefficient and thyroid tissue structure in rats with GC and different kinds of HZ antagonistic medicaments plus or minus the antagonistic medicaments of Haizao Yuhu Decoction containing 5 times of the prescribed high dose in Chinese Pharmacopoeia of antagonistic medicaments has significant effect.Its mechanism may be related to the promotion of thyroid cell apoptosis.There was no significant difference in addition or subtraction of antagonistic medicaments and among different HZ varieties.