| Objective:To explore the mechanism and correlation between s HT and cardiac function Through two parts of clinical experiment and basic experiment,and to determine the effect of L-T4 Substitution treatment on cardiac dysfunction in s HT.Methods:The newly diagnosed sHT,Hypothyroidism patients and normal volunteers of Gansu province people's hospital at January 2015-March 2017 participated in Clinical trials.To observe the heart function of patients with sHT change situation through statistical analysis of Echocardiography index,such as EF,FS,E peak,A peak and some clinical data.Sixty-five male Wistar rats were randomly divided into five groups:control group,sHT A,B,C group and sHT+T4 group.The sHT A,B,C rats were induced by methimazole and respectively gave 5 mg·kg-1·d-1?15 mg·kg-1·d-1?20 mg·kg-1·d-1.The sHT+T4 rats were administered L-T4 treatment after 8 weeks of MMI administration.Serum TT4,and TSH were detected by radioimmunoassay kits and ELISA kits;Left ventricular function was measured by Power Lab system via subclavian artery catheter.The expressi on of Serca2a and Ryr2 were detected by RT-PCR,Western bolt,Immunohistochemistry.Results:Clinical Trial1.The total number of patients included in clinical trial was 104 sHT patients,76Hypothyroidism patients and 100 normal volunteers.2.There was no significant difference in age and systolic blood pressure between the each group.Compared with the control group,the TSH level of the sHT A group,s HT B group and the Hypothyroidism group was significantly increased?P<0.05?.The level of FT3 in Hypothyroidism group was significantly lower than that in other three groups?P<0.05?.The diastolic pressure in the s HT B group was significantly higher than that in the control group?P<0.05?.3.There was no significant difference in EF and FS between each group?P>0.05?.Compared with the control group,the values of E and A were significantly decreased in the s HT group and the Hypothyroidism group?P<0.05?.Animal Experiment1.There were no significant differences in the serum TT4 between each group.The serum TSH level in the sHT groups?A,B,and C?were significantly increased compared with that in the control group?P<0.05?.In s HT+T4 group,the serum TSH level was statistically decreased compared with sHT C group?p<0.05?,but still increased compared with control group?P<0.05?.2.The sHT rats had a significant decrease in ventricular pressure and HR compared with the control group rats.The L-T4 treatment rats had higher ventricular pressure and HR compared with the other group rats.Pearson correlation showed a negative correlations were found between TSH and LVSP?r=-0.706,P<0.01?,LVEDP?r=-0.857,P<0.01?,MP?r=-0.841,P<0.01?and HR?r=-0.855,P<0.01?.3.Compared with control group,the activity of Ryr2 and Serca2a decreased by 29.34%and 30%in s HT A group?P<0.05?,decreased by 67.18%and 53.64%in s HT B group?P<0.001?,decreased by 78.31%and 68.57%in sHT C group?P<0.001?.4.In HE staining,myocardial fibers of rats in control group were arranged regularly and contacted closely with cell space and the nuclear chromatin toward laid the center with the even distribution.But the structure of the cardiac muscle of rats in sHT C group was loose and has a disordered arrangement.Some cardiac cells got swelling and plasma cell infiltration could be observed in cell space.In sHT A and B group,those changes were relatively better than that in s HT C group.In s HT+T4 group,morphological changes of myocardial cells was better than that in s HT groups,especially better than high serum TSH groups.Conclusion:Our study demonstrated that left ventricular function was impaired in s HT rats through regulating the activity of Serca2a,Ryr2,and the high level of TSH plays a key role in this process.TSH levels act on cardiac muscle for a long time which could weaken the ability of myocardial systolic and diastolic.L-T4 treatment has a beneficial effect for restoring cardiomyocytes and recovering left ventricular function in early impaired stage. |
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