| Objective Hypothyroidism is a common, difficult and complicated disease of endocrine system, which is a syndrome of hypometabolism caused by the deficiency of the synthesis, secretion or biological effect of thyroid hormone. Until now, there are no radical therapeutic methods for it in clinic. Chinese medicine may bring significant therapeutic effect on it. To take vigorous action on searching for a new therapeutic method for prevention and treatment of hypothyroidism by giving full display to the advantages of Traditional Chinese Medicine such as whole adjustment, less side effect, and long-term therapeutic effective, on the base of the clinical practice with Youguiwan, we study the function of Youguiwan on hypothyroidism and its mechanism under the basic theory and experimental methods of modern medicine with the experimental hypothyroidism animal model in order to provide a theory and experimental base for the clinical practice.Methods Seventy female rats were randomly divided into 7 groups, I.e. the model group(experimental hypothyroidism group), the western medicine group(thyroxin group), the small dosage group of Youguiwan , the middle dosage of Youguiwan, the large dosage of Youguiwan, and the integrated group of thyroxin and Youguiwan, the normal control group. Each group had 10 rats. The rats of the fronting 6 groups were made model by infusing 0.1% propylthiouracil (PTU);1ml/100g/day for 10 weeks(qod for the latter 8 weeks). After 2 weeks, the rats were treated with corresponding medicines for 8 weeks. Then the followingdetection were taken out: direct chemiluminescent on serum FT3, FT4? T3,T4, sTSH and adrenal cortical hormone hormones(Cor), adrenocorticotropic hormone(ACTH);RT-PCR on the gene expression of glucose transporter-4(GluT-4)mRNA in skeletal muscle and cardiac muscle tissue and light microscope to observe the pathologic change in thyroid gland, pituitary gland and adrenal gland;immunohistochemical method on the content or express of bcl-2/bax which is correlated with apoptosis in thyreoid follicular cell. Results1. After 15 days of infusing PTU, the model rats showed up the behavior change of hypothyroidism, as well as the deficiency of Yangqi in the kidney of Traditional Chinese Medicine. The level of T3, T4, FT3, FT4 which can imply the severe degree of hypothyroidism was low and as negative feedback, the level of sTSH was high. Meanwhile, the thyroid had retrograte changes in pathology. Youguiwan, especially the low and middle dosage had not only improved the symptoms of hypothyroidism, but also increased the content of T3 and FT3, decreased the content of sTSH, at the same time, and improved the retrograte changes of the thyroid.2. In the rats of model group, the level of plasma cortisol was decreased and the level of serum ACTH was stepped up. After treatment, the content of plasma cortisol was increased, but neither group had obvious therapeutic efficacy (P > 0.05). The level of serum ACTH was decreased in each handled group, especially in the large dosage of Youguiwan group, the integrated group of thyroxin and Youguiwan , and the empirical formula group(P< 0.01). At the same time, the zona fasciculata of adrenal gland gave up different extent hyperplasia, especially in the thyroxin group,the integrated group of thyroxin and Youguiwan .3. In the rats of model group, the expression level of GluT-4 mRNA in the skeletal muscle was obviously decreased, approximately 14.37% of the normal level. After treatment, it was stepped up close to the normal level in the group of middle dosage of Youguiwan , the large dosage of Youguiwan, and the integrated group of thyroxin and Youguiwan (P < 0.01). For the rest group, they had low expression level like the model groupCP > 0.05). Meanwhile, the expression level of GluT-4 mRNA in the cardiac muscle of model rats was obviously decreased, too, approximately 15.13% of the normal level. After treatment, it was stepped up close to the normal level in the group of middle dosage of Youguiwan , and the integrated group of thyroxin and Youguiwan (P< 0.01). For the rest group, they had low expression level like the model group(P > 0.05).4. Bcl-2, which is mainly located in the substance of thyreoid follicular epithelial cell, is universally expressed in the normal thyroid tissue. In the rats of model group, the expression level of bcl-2 was obviously decreased, and had significant difference with the normal group(P< 0.01). Compared with the model group, the expression level of bcl-2 was obviously stepped up obviously close to the normal level in each treated group, and there had no significant difference among them(/> > 0.05). Bax, also mainly located in the substance of thyreoid follicular epithelial cell, is obviously expressed in the active proliferation region and does not expressed in the normal thyroid tissue. In the rats of model group, the expression level of bax was obviously increased, and had significant difference with the normal group(P < 0.01). Compared with the model group, the expression level of bax was obviously stepped down close to the normal level in each treated group, especially inthe integrated group of thyroxin and Youguiwan(/> < 0.01).5. From the experiment we found Youguiwan had no hepatotoxicity and renal toxicity, so it is security and validity.Conclusions Youguiwan, which may inspire yang-qi to promote the functional activity of the body, had good therapeutic effect on hypothyroidism rats, through lessening symptoms, increasing of thyroid hormone, correcting the hypoadrenocorticism which was caused by hypothyroidism by recovering the endocrine secretion of adrenal gland and the improvement of the retrograte change of thyroid, pituitary gland and adrenal gland. Youguiwan can improve energy metabolism by up-regulating the expression of GluT-4 in the skeletal muscle and cardiac muscle tissue of model rats, and another, Youguiwan can keep the normal apoptosis procedure by recovering the balance of bcl-2 / bax in follicular cells of thyroid, and this may be the mechanism of Youguiwan on hypothyroidism. From the experiment we found Youguiwan had no hepatotoxicity and renal toxicity, so it is security and validity.
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