The Expression And Significance Of Nitric Oxide, Nitric Oxide Synthase, Endothelin-1, Transforming Growth Factor Beta1 In Myocardium Of Hyperthyroidism Rats

Objective:To study the expression of nitric oxide(NO), nitric oxide synthase(NOS), endothelin-1(ET-1), transforming growth factor beta1 (TGF-β₁)in myocardium tissue of hyperthyroidsm rats, approach the contribution and significance of factors aboved in the course of hyperthyroid heart, as well as the correlation of the factors aboved .Method:The model of hyperthyroidism rats were established by giving Levothyroxine Sodium(L-T4),during which all rats ate and drank freely. The control group(A1,A2,A3) and the hyperthyroidism group(B1,B2,B3) were killed at 25thday, 45thday and 60thday respectively, to observe the pathology condition and imparement degree of myocardium.The content of nitric oxide and nitric oxida synthese of myocardium were demonstrated by enzymic method, and the immunohistochemist- ry was used to detect the expression of ET-1 and TGF-β₁.Results:1 symptom and physical sign:The eating, drinking, mental state, daily activities, urination and defecation of rats are all normal and of no change in three control groups, and in which the body weights of rats increased stablely. Rats in hyperthyroidism groups, appetite was better, urination and defecation were more, and the seded contained undisgested food was pasty, pelage was no burnrish and a bulk of rats showed the phenomenon of depilation, most of rats were panic, restless, irritated and with muscle microtremored; the body weight of nearly all rats in hyperthyroidism groups was significantly less than that in homeochronous control group(P<0.05).2 The thyroid function examination:The level of FT₃ and FT₄ of three hyperthyroidism groups were significantly more increased than control groups(P<0.01),and which aggravated progressively.The level of TSH was also more significantly decreased than homeochronous control group(P<0.01) and aggravated progressively.3 The value of biochemistry in blood:Myocardial enzyme: The level of CK, CK-MB, AST of hyperthyroidism group was more significantly increased than homeochronous control group(P<0.01) and aggravated progressively from group B1 to group B3. The level of LDH was more increased than control group at group B2 and B3 except group B1. The level ofα-HBDH only was more increased at group B3 than homeochronous control group(P<0.05).4 The examination of heart weight and heart mass index (HW/BW):The value of HW in group B1 incresed but was no statistical significance, and was more significantly increased in group B2 and B3 than that in homeochronous control groups (P<0.01)and aggravated progressively; The proportionality of HW/BW in group B1 was significant increased than that in control group(P<0.01) and aggravated progressively at group B2 and group B3.5 Pathological change of myocardium:Light microscope: In the control group, cardiac muscle fibers lined up regularly, the structure was clear, nucleus was ellipse ; the interspaces between myocardial cells were tight and the nucleus was toroid, the size and shape was regular, during interstitium,the cells of vessel wall were monolayer and lined up regularly. In hyperthyroidism group, cardiocytes lined up disordered, hypertrophia and cloudy swelling, endochylema was dyed lightly. The nucleus were augment and loose significantly. The interstitial substance was desmoplasia and hyperaemia, cardiac muscle fibers were abrupt and branched much, and gaps between fibers were widened. In the interstitial substance, vessel wall thichened, heterophil granulocyte and leukomonocyte infiltrated.6 Determination of NO, NOS :The level of NO, cNOS, iNOS were all not statistically significant at group B1 compared to control group, and the level of NO, cNOS were more significantly decreased in group B2 and B3 (P<0.01)and aggravated progressively, the level of iNOS was more significantly increased in group B2(P<0.05) and B3(P<0.01) and aggravated progressively than homeochronous control group.7 The results of determination of ET-1 and TGF-β1:The expression of ET-1 enhanced in hyperthyroidism groups and aggravated progressively from group B1(P<0.05) to group B3(P<0.01); The expression of TGF-β1 was not statistically significant at group B1 compared to group A1, and enhanced at group B2 and B3(P<0.01) more than homeochronous control group.8 Linear correlation between the thyroid function and all factors determined:The level of CK, CK-MB, AST, LDH were significantly positive correlated with FT₃, FT₄(P<0.01), and negative correlation with TSH(P<0.01); the level ofα-HBDH was only correlated with FT4(P<0.05), and of no correlation with FT₃,TSH.The proportionality of HW/BW was significantly positive correlated with FT₃, FT₄(P<0.01), and negative correlated with TSH(P<0.01).There were significant negative correlation between NO, cNOS and FT₃, FT₄(P<0.01), significant positive correlation between NO, cNOS and TSH(P<0.01); the level of iNOS was significantly positive correlated with FT₃, FT₄(P<0.05), and positive correlated with TSH(P<0.01).The value of average grey scale of ET-1, TGF-β1 were significantly negative correlated with FT₃, FT₄(PET-1 <0.01, P_TGF-β1<0.01), and positive correlated with TSH(PET-1 <0.01,P_TGF-β1<0.01).9 Other results of linear correlation:The value of CK, CK-MB, AST, LDH were significantly negative correlated with the value of average grey scale of ET-1, TGF-β₁(P<0.01), there was no correlation betweenα-HBDH and ET-1, TGF-β₁.The proportionality of HW/BW was significantly negative correlated with the value of average grey scale of ET-1, TGF-β₁(P<0.01).The level of NO, cNOS were positive correlated with the value of average grey scale of ET-1, TGF-β₁; and iNOS was negative correlated with ET-1, TGF-β₁(the value of average grey scale).The result of correlation showed there was significant positive correlation between ET-1 and TGF-β₁(P<0.01).Conclution: This study made the model of hyperthyroidism through giving L-T4 continuously, and rats in model groups showed symptoms of hyperthyroidism which were consistent with the thyroid function. With the development of disease ,rats in hyperthyroidism groups showed myocardial damage which contained myocardial hypertrophy, the higher heart weight, the higher proportionality of HW/BW and creatases. With the lasting course of disease, the heart injury was serious more and more. Through observing myocardial morphous, creatases in blood, and the expression of NO, NOS, ET-1, TGF-β₁ in dynamic state and analyzing correlation between factors aboved, indicated that NO, NOS, ET-1, TGF-β₁ were monmentous in the course of morbility of hyperthyroid heart, and in which they were intercommunicated, interacted and interencouraged.