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The Principle of Preventive and Therapeutic Effect on Treating Experimental Subclinical Hypothyroidism Rat by Wenshenfang

Author: YangRuiXia
Tutor: ChenRuQuan
School: Hubei University of Chinese Medicine
Course: Chinese medical science
Keywords: Subclinical hypothyroidism the T3of myocardial tissue Thyroid hormone receptor The myosin heavy chain Myocardialcollagen Myocardial tissue pathological Myocardial apoptosis TheTCM of wenshenfang Rat
CLC: R259
Type: PhD thesis
Year: 2012
Downloads: 99
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Abstract


Objective:It is constantly a controversy clinical focus on whether SCH needs therapy and how to treat it.TCM has effects on treating SCH by its special theory. This topic, based on the old thoery of chinese traditional medicine, linked professor Chen’s clinical experience, will observe the heart impacts of SCH by experimental SCH rats, resected thyroid tissue and replaced therapy of L-T4. We will reseach the influence and affected principle about wenshenfang, and provide theory evidence for treating SCH and advance the theory of treating SCH by warming Yang Kidney tonifying therapy.Methods:(1)To find out the treatment of SCH from the Deficiency of Kidney Yang, based on the old theory and the contemporary cl inical experience and the experimental research results.(2) To explore the effective methods and regulations of medicine usage in treating SCH by cl inical analyzing of Professor Chen Who treats them by syndrome differentiation.(3)48experimental SCH wistar rats,made by resected thyroid tissue and replaced therapy of L-T4, were divided into6groups, the blank control group and the model group are fed by distilled water(5ml/Kg)everyday, the group treated by low-dose wenshenfang(11.25g/Kg) everyday, the group treated by high-dose wenshenfang (16.88g/Kg) everyday, the group treated by L-T4(4.5μ g/Kg) everyday and the group treated by L-T4(2.25μg/Kg) and wenshenfang (11.25g/Kg) everyday. The forage, the water and the replaced therapy of L-T4are same as before during the gavage. The rats’weight,activity, coat colour and stool are observed.On31st days morning, the rats are killed for examinations:sampled blood from the abdominal aorta for analysis of serum FT3、FT4and TSH. Take out the hearts and examine T3with ELISA in the light of instruction of T3kit. The gene expression o f thyroid hormone receptor andmyosin heavy chain are examined. The concentration of calcium was assessed and cardiomyocyte apoptosisthe pathomorphological change of heart were researched. The effects on the index of Wenshenfang are observed as well.Results:(1) Deficiency of Kidney Yang in spite of induced by congenital gift or acquired disorders can lead to the occurrence and development of SCH, the theory can be afforded that the treatment of SCH from the deficiency of Kidney Yang.(2) Professor Chen has succeeded in treating SCH on the theory of deficiency of Kidney Yang.(3) It is found that:Compared with the blank control group, the body weight of the other groups is increased; compared with the model group, the body weight of the group treated by L-T4everyday, the group treated by L-T4and wenshenfang everyday and the group treated by high-dose wenshenfang everyday incresed markedly (P <0.01).The level of the rat’s FT3、FT4of each treatment group has not significant changes compared with the blank control group (P>0.05), the level of TSH of each treatment group has reduce markedly (P<0.01), has no significant changes compared with the blank control group (P>0.05)(4) It is found that:Compared with the blank control group, the T3of myocardial tissue of the model group reduced (P<0.01); compared with the model group, the T3of myocardial tissue of the group treated by high-dose wenshenfang everyday has raised markedly(P<0.05), approximately same as the blank control group’s (P>0.05). Thyroid hormone receptor isoforms T α1、T β1gene expression of the model group reduced markedly and Tα2gene expression raised (P<0.01)compared with the blank control group. Compared with the model group, thyroid hormone receptor isoforms Tα1、T β1gene expression of the group treated by L-T4and wenshenfang everyday raised and Tα2gene expression reduced (P <0.05), wenshenfang has effect on reducing Tα2gene expression and raising Tβ1gene expression (P<0.05). The levels of Tα2、 Tβ1gene expression of the group treated by L-T4and wenshenfang and the group treated by high-dose wenshenfang everyday are approximately same as that of the blank control group’s (P>0.05).The treatment of L-T4and wenshenfang is better than that of high-dose wenshenfang on reducing Tα1gene expression.(5) It is found that:Compared with the blank control group, α-MHCmRNA expression reduced (P<0.05), β-MHCmRNA expression raised (P<0.01); compared with the model group, α-MHCmRNA expression of the group treated by L-T4and wenshenfang everyday and the group treated by high-dose wenshenfang everyday has raised, β-MHCmRNA expression reduced(P<0.05), approximately same as the blank control group’s (P>0.05)(6) It is found that:Compared with the blank control group, the content of myocardial hydroxyproline and collagen reduced (P<0.01); compared with the model group, the content of myocardial hydroxyproline and collagen of the group treated by L-T4everyday, the group treated by L-T4and wenshenfang everyday and the group treated by high-dose wenshenfang everyday has raised (P<0.01), and the content of the group treated by high-dose wenshenfang everyday approximately same as the blank control group1s (P>0.05)The rat’s myocardial tissue after he-stained enlarged400times through microscope, we inspected that the cardiac muscle cells arrangement is neat, the cell size is homogeneous, the cell muscle striations clearly in the blank control group. The myocardial cells derangement, in the model group, and some cells swell significantly compared with the blank control group. The change of the group treated by low-dose wenshenfang everyday falls in between the two groups mentioned, only several swelling cardiac muscle cells. The cells of the group treated by L-T4everyday, the group treated by L-T4and wenshenfang everyday and the group treated by high-dose wenshenfang everyday are approximately same as that of the blank control group.We inspected that the rat’s the cardiac muscle cells nuclei of the blank control group had not apparent change through the transmission electron microscope, and cytokinesis in the arrangement of collagen fibers in good, myocardial cells each with apparent sarcomere, mitochondria swollen, sarcoplasmic reticulum without dilatation. The model group rats cardiac tissue muscle nuclei is irregular.Chromatin margination, cytokinesis in markedly swollen mitochondria, the mitochondrial cristae of injury, fracture, forming irregular enlargement of gap, mitochondrial matrix dissolution, sarcoplasmic reticulum swelling, visible sarcomere, but the band are not obvious myotome. The group treated by low-dose wenshenfang everyday in myocardial tissues of rats had mild irregular shrinkage of nucleus, the perinuclear space increases, no obvious changes in the cytoplasm of myof ibrils, part of the mitochondrial mild swelling, crest clearance broadening, glycogen decreased or disappeared, sarcoplasmic reticulum mild dilatation. The group treated by L-T4everyday, the group treated by L-T4and wenshenfang everyday and the group treated by high-dose wenshenfang everyday in myocardial tissues of rats were with nuclei irregular, perinuclear space locally increasing, cytokinesis in myof ibrillar arrange good, sarcomere is obvious, the band is not obvious myotome, mitochondria swollen, sarcoplasmic reticulum mild dilatation.(7) Compared with the blank control group,the model group of myocardial cells concentration of Ca2+raised markedly (P<0.01), and that of the group treated by high-dose wenshenfang everyday reduced markedly (P<0.05), approximately same as the blank control group’s (P>0.05)Rat cardiac tissue was cut into slices,after died marker, we inspected through microscope enlarged400times. It was found that the model group showed Brown nuclei increased significantly, the blank control group barely,and the other groups several.Conclusion:Deficiency of Kidney Yang is pathological basis of SCH. Warming Yang Kidney tonifying therapy is a remedy of SCH. Professor Chen’s clinical experience gave another evidence of treating SCH by Warming Yang Kidney tonifying therapy. The present experiments indicate that SCH associated with the reduction of the T3of myocardial tissue, abnormal expression of Thyroid hormone receptor, variation of the content of myocardial collagen, structure and function of myocardium in rats. The TCM of wenshenfang could reverse these changes to a certain degree, affected the growth and activity of experimental rats, regulate thyroid function. The TCM of wenshenfang can increase the T3of myocardial tissue, regulate the expression of thyroid hormone receptor, reverse the abnormal expression of of myosin heavy chain, improve the content of myocardial collagen, amend myocardial tissue pathological, relieve calcium overload, and decrease myocardial apoptosis. So wenshenfang has the effect of protecting myocardium. This topic are expected to afford the theory evidence for treating SCH and advance the theory of treating SCH by warming Yang Kidney tonifying therapy.

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